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  Subjects -> PHARMACY AND PHARMACOLOGY (Total: 575 journals)
Showing 1 - 200 of 253 Journals sorted alphabetically
AAPS Journal     Hybrid Journal   (Followers: 24)
AAPS Open     Open Access   (Followers: 4)
AAPS PharmSciTech     Hybrid Journal   (Followers: 6)
AboutOpen     Open Access  
ACS Pharmacology & Translational Science     Hybrid Journal   (Followers: 3)
Acta Pharmaceutica     Open Access   (Followers: 4)
Acta Pharmaceutica Indonesia     Open Access  
Acta Pharmaceutica Sinica B     Open Access   (Followers: 1)
Acta Pharmacologica Sinica     Hybrid Journal   (Followers: 3)
Acta Physiologica Hungarica     Full-text available via subscription  
Actualites Pharmaceutiques     Full-text available via subscription   (Followers: 4)
Advanced Drug Delivery Reviews     Hybrid Journal   (Followers: 96)
Advanced Herbal Medicine     Open Access   (Followers: 8)
Advanced Therapeutics     Hybrid Journal   (Followers: 1)
Advances in Pharmacoepidemiology & Drug Safety     Open Access   (Followers: 2)
Advances in Pharmacological and Pharmaceutical Sciences     Open Access   (Followers: 9)
Advances in Pharmacology     Full-text available via subscription   (Followers: 18)
Advances in Pharmacology and Pharmacy     Open Access   (Followers: 5)
Advances in Traditional Medicine     Hybrid Journal   (Followers: 3)
Adverse Drug Reaction Bulletin     Full-text available via subscription   (Followers: 5)
AJP : The Australian Journal of Pharmacy     Full-text available via subscription   (Followers: 8)
Alternatives to Laboratory Animals     Full-text available via subscription   (Followers: 9)
American Journal of Cardiovascular Drugs     Hybrid Journal   (Followers: 19)
American Journal of Drug Discovery and Development     Open Access   (Followers: 3)
American Journal of Health-System Pharmacy     Full-text available via subscription   (Followers: 55)
American Journal of Pharmacological Sciences     Open Access   (Followers: 1)
American Journal of Pharmacology and Toxicology     Open Access   (Followers: 23)
American Journal of Therapeutics     Hybrid Journal   (Followers: 13)
Analytical Methods     Hybrid Journal   (Followers: 8)
Annales Pharmaceutiques Francaises     Full-text available via subscription  
Annals of Pharmacotherapy     Hybrid Journal   (Followers: 56)
Annual Review of Pharmacology and Toxicology     Full-text available via subscription   (Followers: 37)
Anti-Infective Agents     Hybrid Journal   (Followers: 5)
Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry     Hybrid Journal   (Followers: 5)
Antibiotics     Open Access   (Followers: 10)
Antibody Therapeutics     Open Access  
Antiviral Chemistry and Chemotherapy     Open Access   (Followers: 1)
Antiviral Research     Hybrid Journal   (Followers: 8)
Applied Clinical Trials     Full-text available via subscription   (Followers: 7)
Archiv der Pharmazie     Hybrid Journal   (Followers: 3)
Archives of Drug Information     Hybrid Journal   (Followers: 4)
Archives of Pharmacal Research     Full-text available via subscription   (Followers: 2)
Archives of Pharmacy and Pharmaceutical Sciences     Open Access   (Followers: 1)
Archives of Razi Institute     Open Access  
Archivos Venezolanos de Farmacología y Terapéutica     Open Access  
Ars Pharmaceutica     Open Access  
Asian Journal of Medical and Pharmaceutical Researches     Open Access  
Asian Journal of Pharmaceutical Research and Health Care     Open Access   (Followers: 2)
Asian Journal of Pharmaceutical Sciences     Open Access   (Followers: 1)
Asian Journal of Pharmaceutics     Open Access   (Followers: 1)
Asian Journal of Research in Medical and Pharmaceutical Sciences     Open Access  
ASSAY and Drug Development Technologies     Hybrid Journal   (Followers: 3)
Australian Journal of Herbal Medicine     Full-text available via subscription   (Followers: 4)
Australian Pharmacist     Full-text available via subscription   (Followers: 7)
Autonomic & Autacoid Pharmacology     Hybrid Journal  
Avicenna Journal of Phytomedicine     Open Access   (Followers: 1)
Bangladesh Journal of Pharmacology     Open Access  
Bangladesh Journal of Physiology and Pharmacology     Open Access  
Bangladesh Pharmaceutical Journal     Full-text available via subscription  
Basic & Clinical Pharmacology & Toxicology     Hybrid Journal   (Followers: 14)
Behavioural Pharmacology     Hybrid Journal   (Followers: 2)
Bioanalysis     Full-text available via subscription   (Followers: 11)
Biochemical Pharmacology     Hybrid Journal   (Followers: 11)
BioDrugs     Full-text available via subscription   (Followers: 8)
Biological & Pharmaceutical Bulletin     Full-text available via subscription   (Followers: 3)
Biomarkers in Drug Development     Partially Free   (Followers: 2)
Biomaterials     Hybrid Journal   (Followers: 55)
Biomedical and Environmental Sciences     Full-text available via subscription   (Followers: 1)
Biomedicine & Pharmacotherapy     Full-text available via subscription   (Followers: 2)
Biometrical Journal     Hybrid Journal   (Followers: 9)
Biopharm International     Full-text available via subscription   (Followers: 20)
Biopharmaceutics and Drug Disposition     Hybrid Journal   (Followers: 11)
BMC Pharmacology     Open Access   (Followers: 2)
BMC Pharmacology & Toxicology     Open Access   (Followers: 8)
Brazilian Journal of Pharmaceutical Sciences     Open Access   (Followers: 1)
British Journal of Clinical Pharmacology     Hybrid Journal   (Followers: 30)
British Journal of Pharmacology     Hybrid Journal   (Followers: 17)
British Journal of Pharmacy (BJPharm)     Open Access   (Followers: 2)
Bulletin of Faculty of Pharmacy, Cairo University     Open Access   (Followers: 2)
CADTH Technology Overviews     Free  
Canadian Journal of Pain     Open Access   (Followers: 3)
Canadian Journal of Physiology and Pharmacology     Hybrid Journal   (Followers: 2)
Canadian Pharmacists Journal / Revue des Pharmaciens du Canada     Hybrid Journal   (Followers: 3)
Cancer Biotherapy & Radiopharmaceuticals     Hybrid Journal  
Cancer Chemotherapy and Pharmacology     Hybrid Journal   (Followers: 6)
Cardiovascular Drugs and Therapy     Hybrid Journal   (Followers: 14)
Cardiovascular Therapeutics     Open Access   (Followers: 3)
Cephalalgia Reports     Open Access  
Chemical and Pharmaceutical Bulletin     Full-text available via subscription   (Followers: 1)
Chemical Research in Toxicology     Hybrid Journal   (Followers: 22)
ChemMedChem     Hybrid Journal   (Followers: 11)
Chemotherapy     Full-text available via subscription   (Followers: 3)
Chinese Herbal Medicines     Full-text available via subscription   (Followers: 1)
Chinese Journal of Pharmaceutical Analysis     Full-text available via subscription  
Ciencia e Investigación     Open Access  
Ciência Equatorial     Open Access  
Clinical and Experimental Pharmacology and Physiology     Hybrid Journal   (Followers: 7)
Clinical and Translational Science     Open Access   (Followers: 4)
Clinical Complementary Medicine and Pharmacology     Open Access  
Clinical Drug Investigation     Full-text available via subscription   (Followers: 8)
Clinical Medicine Insights : Therapeutics     Open Access  
Clinical Neuropharmacology     Hybrid Journal   (Followers: 2)
Clinical Pharmacist     Partially Free   (Followers: 12)
Clinical Pharmacokinetics     Full-text available via subscription   (Followers: 28)
Clinical Pharmacology & Therapeutics     Hybrid Journal   (Followers: 45)
Clinical Pharmacology in Drug Development     Hybrid Journal   (Followers: 4)
Clinical Pharmacology: Advances and Applications     Open Access   (Followers: 6)
Clinical Research and Regulatory Affairs     Hybrid Journal   (Followers: 12)
Clinical Therapeutics     Hybrid Journal   (Followers: 34)
Clinical Toxicology     Hybrid Journal   (Followers: 18)
Clinical Trials     Hybrid Journal   (Followers: 19)
CNS Drug Reviews     Open Access   (Followers: 4)
CNS Drugs     Full-text available via subscription   (Followers: 10)
Combination Products in Therapy     Open Access  
Consultant Pharmacist     Full-text available via subscription   (Followers: 2)
Consumer Drugs     Full-text available via subscription  
Contract Pharma     Full-text available via subscription  
Cosmetics     Open Access   (Followers: 4)
CPT : Pharmacometrics & Systems Pharmacology     Open Access   (Followers: 10)
Critical Reviews in Clinical Laboratory Sciences     Hybrid Journal   (Followers: 19)
Critical Reviews in Therapeutic Drug Carrier Systems     Full-text available via subscription   (Followers: 5)
Critical Reviews in Toxicology     Hybrid Journal   (Followers: 26)
Current Bioactive Compounds     Hybrid Journal  
Current Cancer Therapy Reviews     Hybrid Journal   (Followers: 5)
Current Clinical Pharmacology     Hybrid Journal   (Followers: 4)
Current Drug Delivery     Hybrid Journal   (Followers: 6)
Current Drug Discovery Technologies     Hybrid Journal   (Followers: 6)
Current Drug Metabolism     Hybrid Journal   (Followers: 5)
Current Drug Safety     Hybrid Journal   (Followers: 8)
Current Drug Targets     Hybrid Journal   (Followers: 5)
Current Drug Therapy     Hybrid Journal   (Followers: 3)
Current Enzyme Inhibition     Hybrid Journal   (Followers: 1)
Current Issues in Pharmacy and Medical Sciences     Open Access   (Followers: 2)
Current Medical Science     Hybrid Journal  
Current Medicinal Chemistry     Hybrid Journal   (Followers: 13)
Current Molecular Pharmacology     Hybrid Journal  
Current Nanoscience     Hybrid Journal  
Current Neuropharmacology     Hybrid Journal   (Followers: 1)
Current Opinion in Pharmacology     Hybrid Journal   (Followers: 9)
Current Pharmaceutical Analysis     Hybrid Journal   (Followers: 1)
Current Pharmaceutical Biotechnology     Hybrid Journal   (Followers: 10)
Current Pharmaceutical Design     Hybrid Journal   (Followers: 11)
Current Pharmacogenomics and Personalized Medicine     Hybrid Journal   (Followers: 3)
Current Pharmacology Reports     Hybrid Journal  
Current Protocols in Pharmacology     Hybrid Journal  
Current Radiopharmaceuticals     Hybrid Journal   (Followers: 1)
Current Research in Drug Discovery     Open Access   (Followers: 1)
Current Research in Pharmacology and Drug Discovery     Open Access   (Followers: 1)
Current Therapeutic Research     Open Access   (Followers: 6)
Current trends in Biotechnology and Pharmacy     Open Access   (Followers: 8)
Current Vascular Pharmacology     Hybrid Journal   (Followers: 4)
Dhaka University Journal of Pharmaceutical Sciences     Open Access  
Die Pharmazie - An International Journal of Pharmaceutical Sciences     Full-text available via subscription   (Followers: 6)
Dose-Response     Open Access  
Drug and Chemical Toxicology     Hybrid Journal   (Followers: 14)
Drug and Therapeutics Bulletin     Hybrid Journal   (Followers: 9)
Drug Delivery     Open Access   (Followers: 9)
Drug Delivery and Translational Research     Hybrid Journal   (Followers: 2)
Drug Design, Development and Therapy     Open Access   (Followers: 3)
Drug Development and Industrial Pharmacy     Hybrid Journal   (Followers: 30)
Drug Development Research     Hybrid Journal   (Followers: 13)
Drug Discovery Today: Technologies     Full-text available via subscription   (Followers: 13)
Drug Metabolism and Disposition     Hybrid Journal   (Followers: 13)
Drug Metabolism and Pharmacokinetics     Hybrid Journal   (Followers: 6)
Drug Metabolism Letters     Hybrid Journal   (Followers: 3)
Drug Metabolism Reviews     Hybrid Journal   (Followers: 8)
Drug Research     Hybrid Journal   (Followers: 3)
Drug Resistance Updates     Hybrid Journal   (Followers: 3)
Drug Safety     Full-text available via subscription   (Followers: 82)
Drug Safety - Case Reports     Open Access   (Followers: 2)
Drug Target Insights     Open Access  
Drug, Healthcare and Patient Safety     Open Access   (Followers: 10)
Drugs     Full-text available via subscription   (Followers: 114)
Drugs & Aging     Full-text available via subscription   (Followers: 9)
Drugs & Therapy Perspectives     Full-text available via subscription   (Followers: 8)
Drugs : Real World Outcomes     Hybrid Journal   (Followers: 1)
Drugs and Therapy Studies     Open Access  
Drugs in R & D     Full-text available via subscription   (Followers: 2)
Drugs of the Future     Full-text available via subscription   (Followers: 8)
East and Central African Journal of Pharmaceutical Sciences     Open Access   (Followers: 1)
Egyptian Pharmaceutical Journal     Open Access  
EJNMMI Radiopharmacy and Chemistry     Open Access  
EMC - Cosmetologia Medica e Medicina degli Inestetismi Cutanei     Full-text available via subscription  
Emerging Trends in Drugs, Addictions, and Health     Open Access  
Environmental Toxicology and Pharmacology     Hybrid Journal   (Followers: 9)
Epilepsy Research     Hybrid Journal   (Followers: 7)
Ethiopian Pharmaceutical Journal     Full-text available via subscription   (Followers: 1)
EUREKA : Health Sciences     Open Access  
European Journal of Clinical Pharmacology     Hybrid Journal   (Followers: 13)
European Journal of Drug Metabolism and Pharmacokinetics     Hybrid Journal   (Followers: 8)
European Journal of Hospital Pharmacy : Science and Practice (EJHP)     Hybrid Journal   (Followers: 5)
European Journal of Medicinal Plants     Open Access   (Followers: 2)
European Journal of Pharmaceutical Sciences     Hybrid Journal   (Followers: 85)
European Journal of Pharmaceutics and Biopharmaceutics     Hybrid Journal   (Followers: 35)
European Journal of Pharmacology     Hybrid Journal   (Followers: 9)
European Neuropsychopharmacology     Hybrid Journal   (Followers: 8)
European Review for Medical and Pharmacological Sciences     Full-text available via subscription   (Followers: 1)
Experimental and Clinical Psychopharmacology     Full-text available via subscription   (Followers: 7)
Expert Opinion on Drug Delivery     Hybrid Journal   (Followers: 18)
Expert Opinion on Drug Discovery     Hybrid Journal   (Followers: 18)

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Canadian Journal of Physiology and Pharmacology
Journal Prestige (SJR): 0.724
Citation Impact (citeScore): 2
Number of Followers: 2  
 
  Hybrid Journal Hybrid journal (It can contain Open Access articles)
ISSN (Print) 0008-4212 - ISSN (Online) 1205-7541
Published by NRC Research Press Homepage  [19 journals]
  • Paeonol inhibits inflammatory response and protects chondrocytes by
           upregulating sirtuin 1

    • Free pre-print version: Loading...

      Authors: Peng Shang, Ying Liu, Junqing Jia
      Pages: 1 - 8
      Abstract: Canadian Journal of Physiology and Pharmacology, Ahead of Print.
      Paeonol is the bioactive component in Paeonia lactiflora Pall., Cynanchum paniculatum and Paeonia × suffruticosa Andr. Paeonol has been previously demonstrated to inhibit the release of tumor necrosis factor α (TNF-α) and interluekin 6 (IL-6) in chondrocytes. Sirtuin 1 (SIRT1) is downregulated in degraded cartilage and paeonol could induce nuclear accumulation of SIRT1. Therefore, the present study aims to investigate the possible role of paeonol in chondrocyte inflammation and cartilage protection in osteoarthritis (OA) as well as its regulation of SIRT1. Primary chondrocytes from rat knee joints were transfected with short hairpin (sh) – SIRT1 and (or) paeonol prior to IL-1β exposure, and then inflammatory response, apoptosis, and extracellular matrix (ECM) degradation in the cells were evaluated concurrent with the activation of the nuclear factor κβ (NF-κβ) signaling pathway. Increased levels of TNF-α, IL-17, IL-6, matrix metalloproteinase 1 (MMP-1), MMP-3, and MMP-13 along with decreased tissue inhibitor of metalloproteinases 1 and type II collagen levels were found in IL-1β-stimulated chondrocytes. Chondrocyte apoptosis was elevated and the NF-κβ signaling pathway was activated in response to IL-1β treatment. Paeonol enhanced SIRT1 expression to inactivate the NF-κβ signaling pathway, thereby ameliorating inflammatory cytokine secretion, ECM degradation, and chondrocyte apoptosis. In conclusion, the results of the present study confirm the potential of paeonol as a candidate OA drug.
      Citation: Canadian Journal of Physiology and Pharmacology
      PubDate: 2022-03-02T06:57:18Z
      DOI: 10.1139/cjpp-2021-0319
       
  • Protective effects of sildenafil administration on
           chemotherapeutic-induced ovarian damage in rats

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      Authors: Başak Ergin, Gizem Berfin Uluutku, İbrahim Kale, Cumhur Selçuk Topal, Cihan Toğrul, Murat Muhcu
      Pages: 1 - 6
      Abstract: Canadian Journal of Physiology and Pharmacology, Ahead of Print.
      Agents to reduce the gonadotoxic effects of chemotherapeutics are still under investigation. In this context, we aimed to investigate the protective effect of sildenafil against chemotherapeutic-induced gonadotoxicity in a rat model. A total of 62 female rats were divided into eight groups as control, sildenafil (1.4 mg/kg, orally), doxorubicin (3 mg/kg, i.p.), cisplatin (5 mg/kg, i.p.), cyclophosphamide (200 mg/kg, i.p.), doxorubicin+sildenafil, cisplatin+sildenafil, and cyclophosphamide+sildenafil (1.4 mg/kg orally sildenafil in addition to the same dose of chemotherapeutics). The groups were compared in terms of follicle count, ovarian size, and anti-müllerian hormone (AMH) levels. Use of sildenafil with cyclophosphamide was effective only in preserving primary follicle count (p = 0.026) and had no significant change in the secondary follicle count, ovarian size, or AMH level. Adding sildenafil to cisplatin had a significant protective effect on primary follicle count (p = 0.011), secondary follicle count (p = 0.009), and ovarian size (p = 0.001), but this effect could not be demonstrated at AMH level. Sildenafil was not effective on any parameter in the doxorubicin group. Sildenafil may be effective in reducing the gonadotoxicity associated with the use of cisplatin and cyclophosphamide.
      Citation: Canadian Journal of Physiology and Pharmacology
      PubDate: 2022-02-28T08:00:00Z
      DOI: 10.1139/cjpp-2021-0576
       
  • Clinical efficacy and safety of two concentrations of intravenous
           nicardipine hydrochloride for nicardipine-related phlebitis in patients
           with preeclampsia

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      Authors: Fengying Ye, Qiuyun Lu, Bihua Kong, Yanqiu Li
      Pages: 1 - 4
      Abstract: Canadian Journal of Physiology and Pharmacology, Ahead of Print.
      To evaluate the effect of two concentrations of intravenous administration of nicardipine hydrochloride on nicardipine-related phlebitis in patients with preeclampsia. A total of 100 preeclampsia patients were administered with nicardipine hydrochloride and divided into the low-concentration (LC) and high-concentration (HC) groups. The incidence and severity of phlebitis, time from treatment to onset of phlebitis, skin temperature, visual analogue scale (VAS) score, induration, and systemic adverse reactions were compared between two groups. The incidence rate of phlebitis in the LC group was 20% (10/50), significantly lower than 42% (21/50) in the HC group (P < 0.05). Ridit Analysis showed that the severity of phlebitis in the LC group was remarkably lower than that in the HC group (P < 0.05). In the LC group, the time from intravenous administration to onset of phlebitis was longer, the average skin temperature was higher, the VAS score was lower, and the indurated area was smaller than those in the HC group (all P < 0.05). Intravenous infusion of nicardipine hydrochloride with constant and low concentration reduces the incidence rate of phlebitis, prolongs the time from treatment to onset of phlebitis, alleviates the severity of phlebitis and pain, maintains skin temperature, and minimizes induration in preeclampsia patients without systemic adverse reactions.
      Citation: Canadian Journal of Physiology and Pharmacology
      PubDate: 2022-02-25T08:53:10Z
      DOI: 10.1139/cjpp-2021-0387
       
  • Endothelial colony forming cells’ tetrahydrobiopterin level in coronary
           artery disease patients and its association with circulating endothelial
           progenitor cells

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      Authors: Atanu Sen, Himani Thakkar, Vinnyfred Vincent, Sandeep Rai, Archna Singh, Sujata Mohanty, Ambuj Roy, Lakshmy Ramakrishnan
      Pages: 1 - 13
      Abstract: Canadian Journal of Physiology and Pharmacology, Ahead of Print.
      Endothelial colony forming cells (ECFCs) participate in neovascularization. Endothelial nitric oxide synthase (eNOS) derived NO· helps in homing of endothelial progenitor cells (EPCs) at the site of vascular injury. The enzyme cofactor tetrahydrobiopterin (BH4) stabilizes the catalytic active state of eNOS. Association of intracellular ECFCs biopterins and ratio of reduced to oxidized biopterin (BH4:BH2) with circulatory EPCs and ECFCs functionality have not been studied. We investigated ECFCs biopterin levels and its association with circulatory EPCs as well as ECFCs proliferative potential in terms of day of appearance in culture. Circulatory EPCs were enumerated by flowcytometry in 53 coronary artery disease (CAD) patients and 42 controls. ECFCs were cultured, characterized, and biopterin levels assessed by high performance liquid chromatography. Appearance of ECFCs’ colony and their number were recorded. Circulatory EPCs were significantly lower in CAD and ECFCs appeared in 56% and 33% of CAD and control subjects, respectively. Intracellular BH4 and BH4:BH2 were significantly reduced in CAD. BH4:BH2 was positively correlated with circulatory EPCs (p = 0.01), and negatively with day of appearance of ECFCs (p = 0.04). Circulatory EPCs negatively correlated with ECFCs appearance (p = 0.02). These findings suggest the role of biopterins in maintaining circulatory EPCs and functional integrity of ECFCs.
      Citation: Canadian Journal of Physiology and Pharmacology
      PubDate: 2022-02-18T08:00:00Z
      DOI: 10.1139/cjpp-2021-0548
       
  • Correction: Antioxidant and anti-inflammatory properties of alpha-lipoic
           acid protect against valproic acid–induced liver injury

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      Authors: Marwa Abdeltawab Mohammed, Doaa Mostafa Gharib, Hoda Ramadan Reyad, Alaa Aboud Mohamed, Fadwa A. Elroby, Hoda Sayed Mahmoud
      Pages: 1 - 1
      Abstract: Canadian Journal of Physiology and Pharmacology, Ahead of Print.

      Citation: Canadian Journal of Physiology and Pharmacology
      PubDate: 2022-02-09T08:00:00Z
      DOI: 10.1139/cjpp-2021-0768
       
  • The effect of the long-term inhibition of hydrogen sulfide production on
           the reactivity of the cardiovascular system in Wistar rats

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      Authors: Magdalena Drobna, Andrea Berenyiova, Sona Cacanyiova
      Pages: 1 - 9
      Abstract: Canadian Journal of Physiology and Pharmacology, Ahead of Print.
      In this study, we investigated the blood pressure responses of the peripheral bed in vivo after chronic hydrogen sulfide (H2S) inhibition combined with acute nitric oxide (NO) deficiency. We also evaluated the role of endogenously produced H2S in the vasoactive responses of large- and medium-sized arteries in vitro. Changes in integrated blood pressure responses were measured after chronic inhibition of cystathionine-γ-lyase, an enzyme involved in H2S synthesis, with DL-propargylglycine (PPG), and acute inhibition of NO-synthase with nonspecific L-NG-nitro arginine methyl ester (L-NAME), and vasoactive responses of the thoracic aorta (TA) and mesenteric artery (MA) were investigated after acute incubation with PPG. We confirmed that chronic H2S deficiency had no effect on blood pressure, heart trophycity, noradrenaline, and H2S donor vasoactive responses but induced renal hypertrophy and a decrease in acetylcholine-induced hypotensive and L-NAME-induced hypertensive responses. Acute H2S deficiency led to an increase in basal tone (MA) or active tone (TA), whereas endothelium-dependent vasorelaxation remained unaffected. Long-term administration of PPG revealed a role of endogenous H2S in the bioavailability of endothelial NO in peripheral arteries. When both H2S and NO were lacking, the activation of H2S-independent compensatory mechanisms plays an important role in maintaining the vasodilator responses of the cardiovascular system.
      Citation: Canadian Journal of Physiology and Pharmacology
      PubDate: 2022-02-01T08:00:00Z
      DOI: 10.1139/cjpp-2021-0251
       
  • Evaluation of the in vivo and in vitro anti-inflammatory activity of a new
           hybrid NSAID tetrahydropyran derivative

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      Authors: Gabriela Mastrangelo Gonçalves, Joyce Mattos de Oliveira, Thayane Ferreira da Costa Fernandes, Roberto Laureano-Melo, Wellington da Silva Côrtes, Saulo Luis Capim, Mário Luiz Araujo de Almeida Vasconcellos, Bruno Guimarães Marinho
      Pages: 1 - 11
      Abstract: Canadian Journal of Physiology and Pharmacology, Ahead of Print.
      Evaluate the anti-inflammatory activity in vivo and in vitro of cis-(±)-acetate of 4-chloro-6-(naphtalene-1-yl)-tetrahydro-2H-pyran-2-yl) methyl 2-(2-(2,6-diclorofenylamine) phenyl (LS19). Male Swiss mice were analyzed in the paw edema, ear edema, and air pouch tests, and in vitro COX inhibition, cytotoxicity evaluation, and cytokine and nitric oxide determination tests. The compound showed effect on the carrageenan- and bradykinin-induced paw edema and capsaicin-induced ear edema tests. In addition, the compound was able to inhibit leukocyte migration to decrease the levels of the pro-inflammatory cytokines tumor necrosis factor α (TNF-α) and interleukin 1β (IL-1β) and to increase the levels of the anti-inflammatory cytokine IL-10. The compound was also able to reduce levels of TNF-α, IL-6, and nitric oxide in the RAW 264.7 cell line and to inhibit COX activity. LS19 did not induce any significant changes in the viability of RAW 264.7 cells, demonstrating safety for these cell lines. The compound LS19 did not reduce the production of gastric mucus and induced a smaller increase in the extent of gastric lesions than that developed by the administration of diclofenac. In summary, the new compound proved to be safer and it had additional mechanisms compared to diclofenac.
      Citation: Canadian Journal of Physiology and Pharmacology
      PubDate: 2022-01-24T09:45:43Z
      DOI: 10.1139/cjpp-2021-0437
       
  • Doxorubicin-induced apoptosis enhances monocyte infiltration and adverse
           cardiac remodeling in diabetic animals

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      Authors: Chandrakala Aluganti Narasimhulu, Dinender K. Singla
      Pages: 1 - 12
      Abstract: Canadian Journal of Physiology and Pharmacology, Ahead of Print.
      Diabetic cancer patients were treated with doxorubicin (DOX), a potent chemotherapeutic drug that induces cardiac toxicity; however, molecular mechanisms of cardiac toxicity in this specific disease progression in patients and animal models are completely unknown. Therefore, we designed a study to understand the effects of DOX-induced cardiac toxicity in diabetic animals and the involved pathophysiological mechanisms. C57BL/6 J mice were divided into four DOX- and diabetic (streptozotocin; STZ) – treated groups; control, STZ, DOX, and DOX+STZ. At day 14, animals were sacrificed, echocardiography was used to examine heart function, and heart and blood samples were collected to investigate apoptotic mechanisms (caspase 3, BAX, B-Cell leukemia/lymphoma 2 (Bcl2)), inflammation, and cardiac remodeling. Our data shows a significant (p < 0.05) increase in glucose levels, apoptotic markers, and monocyte infiltration at the site of apoptosis and triggered inflammatory immune response (tumor necrosis factor α (TNF-α) and interleukin 6 (IL-6)), in DOX+STZ animals compared with control and experimental groups. We also observed significant (p < 0.05) increase in myofibrillar area, fibrosis, and significantly decreased (p < 0.05) cardiac function in DOX-treated diabetic animals compared with controls. In conclusion, our data suggest that DOX induces significantly increased apoptosis, fibrosis, and structural alterations in diabetic hearts compared with non-diabetic animals.
      Citation: Canadian Journal of Physiology and Pharmacology
      PubDate: 2021-12-21T08:00:00Z
      DOI: 10.1139/cjpp-2021-0596
       
  • Delta-tocotrienol enhances the anti-tumor effects of interferon alpha
           through reactive oxygen species and Erk/MAPK signaling pathways in
           hepatocellular carcinoma cells

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      Authors: Alvaro Lucci, Marina C. Vera, Carla G. Comanzo, Florencia Lorenzetti, Anabela C. Ferretti, María Paula Ceballos, Ariel D. Quiroga, María de Luján Alvarez, María Cristina Carrillo
      Pages: 1 - 11
      Abstract: Canadian Journal of Physiology and Pharmacology, Ahead of Print.
      The complexity of hepatocellular carcinoma (HCC) signaling and the failure of pharmacological therapeutics reveal the significance of establishing new anti-cancer strategies. Interferon alpha (IFN-α) has been used as adjuvant therapy for reducing HCC recurrence and improving survival. Delta-tocotrienol (δ-tocotrienol), a natural unsaturated isoform of vitamin E, is a promising candidate for cancer treatment. In this study, we evaluated whether the combination of δ-tocotrienol with IFN-α displays significant advantages in the treatment of HCC cells. Results showed that the combination significantly decreased cell viability, migration and invasion of HCC cells compared with single therapies. Combining δ-tocotrienol and IFN-α enhanced the decrease in proliferating cell nuclear antigen (PCNA) and matrix metalloproteinase (MMP) 7 and MMP-9. The combination also produced an enhancement of apoptosis together with increased Bax/Bcl-xL ratio and reactive oxygen species (ROS) generation. δ-tocotrienol induced Notch1 activation and changes in Erk and p38 MAPK signaling status. Blocking experiments confirmed that ROS and Erk are involved, at least in part, in the anti-cancer effects of the combined treatment. In conclusion, the combination of δ-tocotrienol with IFN-α therapy showed promising results for HCC cell treatment, which makes the combination of cytokine-based immunotherapy with natural products a potential strategy against liver cancer.
      Citation: Canadian Journal of Physiology and Pharmacology
      PubDate: 2021-12-21T08:00:00Z
      DOI: 10.1139/cjpp-2021-0606
       
  • Two-month administration of methylphenidate improves olfactory sensitivity
           and suppresses appetite in individuals with obesity

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      Authors: Fatmé El Amine, Brandon Heidinger, Jameason D. Cameron, Kaamel Hafizi, Shakibasadat BaniFatemi, Philippe Robaey, Régis Vaillancourt, Gary S. Goldfield, Éric Doucet
      Pages: 1 - 9
      Abstract: Canadian Journal of Physiology and Pharmacology, Ahead of Print.
      Olfaction contributes to feeding behaviour and is modulated by changes in dopamine levels. Methylphenidate (MPH) increases brain dopamine levels and has been shown to reduce appetite and promote weight loss in patients with attention deficit hyperactivity disorder. The objectives of this study were to test the effect of MPH on olfaction, appetite, energy intake, and body weight (BW) on individuals with obesity. In a randomized, double-blind study, 12 participants (age 28.9 ± 6.7 years) with a body mass index (BMI) of 36.1 ± 4.5 kg/m2 were assigned to MPH (0.5 mg/kg) (n = 5) or placebo (n = 7) twice daily for 2 months. Appetite (visual analog scale), odour threshold (Sniffin’ Sticks®), energy intake (food menu), and BW (DEXA scan) were measured at day 1 and day 60. MPH intake significantly increased odour threshold scores (6.3 ± 1.4 vs. 9.4 ± 2.1 and 7.9 ± 2.3 vs. 7.8 ± 1.9, respectively; p = 0.029) versus placebo. There was a significantly greater suppression of appetite sensations (desire to eat (p = 0.001), hunger (p = 0.008), prospective food consumption (p = 0.003)) and an increase in fullness (p = 0.028) over time in the MPH versus placebo. MPH suppressed appetite and improved olfactory sensitivity in individuals with obesity. These data provide novel findings on the favourable effects of MPH on appetite and weight regulation in individuals living with obesity.
      Citation: Canadian Journal of Physiology and Pharmacology
      PubDate: 2021-12-15T08:00:00Z
      DOI: 10.1139/cjpp-2021-0318
       
  • β-elemene relieves neuropathic pain in mice through the regulation on
           C-X-C motif chemokine receptor 3 and GABAA receptor

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      Authors: Yi Dai, Zhenhua Zeng, Shuo Deng, Sanbao Zou, Tingyang Dou
      Pages: 1 - 10
      Abstract: Canadian Journal of Physiology and Pharmacology, Ahead of Print.
      β-elemene (Bel) is a sesquiterpene compound that has shown potential in the antinociceptive treatment. This study focused on the function of Bel in neuropathic pain relief in mice. A murine model with spared nerve injury (SNI) was established and treated with Bel. The paw withdrawal thresholds in response to mechanical and thermal stimulations were examined using von Frey filaments. The L4-L6 spinal dorsal horn tissue samples were collected for histological examination. Bel treatment reduced the sensitivities of model mice to mechanical and thermal stimulations, and it inhibited activation of microglia and the secretion of inflammatory cytokines including tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and IL-6 in tissues. Bel treatment reduced the expression of nociceptor excitatory N-methyl-D-aspartate receptor (NMDAR), whereas it enhanced the expression of nociceptor inhibitory gamma-aminobutyric acid A (GABAA) receptor to relieve the nociception of mice. The C-X-C motif chemokine receptor 3 (CXCR3) is a downstream molecule mediated by Bel. Either overexpression of CXCR3 or downregulation of GABAA receptor in the tissues aggravated the neuropathic pain in SNI mice which was initially relieved by Bel. In conclusion, this study suggested that Bel might serve as a drug for nociception management by inhibiting CXCR3 and upregulating GABAA receptor. This study may offer novel insights into the field of neuropathic pain relief.
      Citation: Canadian Journal of Physiology and Pharmacology
      PubDate: 2021-12-03T08:00:00Z
      DOI: 10.1139/cjpp-2021-0636
       
  • Long non-coding RNA LINC01194 promotes the inflammatory response and
           apoptosis of lipopolysaccharide-treated MLE-12 cells through the
           miR-203a-3p/MIP-2 axis

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      Authors: Yuyao Shen, Senwei Zhao, Minglei Hua
      Pages: 1 - 10
      Abstract: Canadian Journal of Physiology and Pharmacology, Ahead of Print.
      Acute lung injury (ALI) induced by bacteria lipopolysaccharide (LPS) is characterized by the upregulation of the apoptosis rate of tissue cells and aggravation of inflammatory response. Although many studies have focused on the pathogenesis of this disease, its mechanism remains unknown. This study examined the regulatory role of long non-coding RNA (lncRNA) LINC01194 in the progression of ALI through various bioinformatics analyses and experimental work, including ELISA assay, dual-luciferase reporter assay, biotinylated RNA pull-down assay, and Western blot analysis. The result showed that the LINC01194 was overexpressed in the ALI-induced mice model. We observed a significant upregulation of LINC01194 in LPS-treated mouse lung epithelial type II cells (MLE-12 cells) after 24 h of induction. Bioinformatics analysis, ELISA assay, quantitative reverse transcription polymerase chain reaction analysis, biotinylated RNA pull-down assay, apoptosis test, and Western blot analysis demonstrated that the LINC01194 could act as a microRNA (miR) miR-203a-3p sponge to activate the inflammatory response in LPS-induced ALI model through post-transcriptional upregulation of macrophage inflammatory protein (MIP-2). We showed that LINC01194 regulates the inflammatory response and apoptosis of LPS-induced mice and MLE-12 cells via the miR-203a-3p/MIP-2 axis. LINC01194 could be a potential biomarker for early diagnosis and the treatment of ALI.
      Citation: Canadian Journal of Physiology and Pharmacology
      PubDate: 2021-12-02T08:00:00Z
      DOI: 10.1139/cjpp-2021-0255
       
  • Comparative effect of vitamin D3 and carbenoxolone treatments in metabolic
           syndrome rats

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      Authors: Nermine Saleh, Ansam Aly Seif, Ienass Bahaa, Enas A. Abdel-Hady
      Pages: 1 - 10
      Abstract: Canadian Journal of Physiology and Pharmacology, Ahead of Print.
      Metabolic syndrome (MetS) is a cluster of cardiovascular risk factors including central obesity, hypertension, insulin resistance, dyslipidemia, and hyperglyemia. MetS is found to be a positive predictor of cardiovascular morbidity and mortality. The present study was planned to test the efficacy of vitamin D3 supplementation as compared with cortisol inhibition on MetS parameters. Wistar rats were allocated into four groups: control, untreated MetS, and MetS treated with either vitamin D3 (10 µg/kg) or carbenoxolone (50 mg/kg). MetS was induced by combination of high-fat diet and oral fructose. After the induction period (8 weeks), MetS was confirmed, and treatment modalities started for a further 4 weeks. Compared with untreated MetS, vitamin D3- and carbenoxolone-treated rats showed significant reduction in blood pressure, body mass index, Lee index, waist circumference, retroperitoneal fat, and improvement of dyslipidemia. Meanwhile, treatment with carbenoxolone significantly lowered the elevated liver enzymes, and vitamin D3 resulted in improved insulin sensitivity, enhanced glucose uptake by muscles, and replenished glycogen content in the liver and muscles near control levels. In conclusion, although treatment with vitamin D3 or carbenoxolone reduced the risk factors associated with MetS, vitamin D3 was effective in ameliorating insulin resistance which is the hallmark of MetS.
      Citation: Canadian Journal of Physiology and Pharmacology
      PubDate: 2021-12-02T08:00:00Z
      DOI: 10.1139/cjpp-2021-0400
       
  • The anti-anginal ranolazine does not confer beneficial actions against
           hepatic steatosis in male mice subjected to high-fat diet and
           streptozotocin-induced type 2 diabetes

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      Authors: Christina T. Saed, Amanda A. Greenwell, Seyed Amirhossein Tabatabaei Dakhili, Keshav Gopal, Farah Eaton, John R. Ussher
      Pages: 1 - 9
      Abstract: Canadian Journal of Physiology and Pharmacology, Ahead of Print.
      Non-alcoholic fatty liver disease (NAFLD) is characterized by the accumulation of excess fat in the liver in the absence of alcohol and increases one’s risk for both diabetes and cardiovascular disease (e.g., angina). We have shown that the second-line anti-anginal therapy, ranolazine, mitigates obesity-induced NAFLD, and our aim was to determine whether these actions of ranolazine also extend to NAFLD associated with type 2 diabetes (T2D). Eight-week-old male C57BL/6J mice were fed either a low-fat diet or a high-fat diet for 15 weeks, with a single dose of streptozotocin (STZ; 75 mg/kg) administered in the high-fat diet-fed mice at 4 weeks to induce experimental T2D. Mice were treated with either vehicle control or ranolazine during the final 7 weeks (50 mg/kg once daily). We assessed glycemia via monitoring glucose tolerance, insulin tolerance, and pyruvate tolerance, whereas hepatic steatosis was assessed via quantifying triacylglycerol content. We observed that ranolazine did not improve glycemia in mice with experimental T2D, while also having no impact on hepatic triacylglycerol content. Therefore, the salutary actions of ranolazine against NAFLD may be limited to obese individuals but not those who are obese with T2D.
      Citation: Canadian Journal of Physiology and Pharmacology
      PubDate: 2021-12-01T08:00:00Z
      DOI: 10.1139/cjpp-2021-0559
       
  • Irisin relaxes rat thoracic aorta: MEK1/2 signaling pathway, KV channels,
           SKCa channels, and BKCa channels are involved in irisin-induced
           vasodilation

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      Authors: Sadettin Demirel, Serdar Sahinturk, Naciye Isbil, Fadil Ozyener
      Pages: 1 - 7
      Abstract: Canadian Journal of Physiology and Pharmacology, Ahead of Print.
      This study investigated the effects of irisin on vascular smooth muscle contractility in rat thoracic aorta, and the hypothesis that mitogen-activated protein kinase kinase (MEK1/2) signaling pathway, voltage-gated potassium (KV) channels, small-conductance calcium-activated potassium (SKCa) channels, and large-conductance calcium-activated potassium (BKCa) channels may have roles in these effects. Isometric contraction-relaxation responses of isolated thoracic aorta rings were measured with an organ bath model. The steady contraction was induced with 10–5 M phenylephrine (PHE), and then the concentration-dependent responses of irisin (10−9−10−6 M) were examined in endothelium-intact and -denuded rat thoracic aortas. Also, the effects of irisin incubations on PHE-mediated contraction and acetylcholine (ACh) – mediated relaxation were studied. Irisin exerted the vasorelaxant effects in both endothelium-intact and -denuded aortic rings at concentrations of 10–8, 10–7, and 10–6 M compared with the control groups (p < 0.001). Besides, pre-incubation of aortic rings with irisin (10 nM, 100 nM, or 1 µM for 30 min) augmented ACh-mediated (10–9–10–5) vasodilation in PHE-precontracted thoracic aorta segments but did not modulate PHE-mediated (10–9–10–5) contraction. In addition, MEK1/2 inhibitor U0126, KV channel blocker XE-991, SKCa channel blocker apamin, and BKCa channel blocker tetraethylammonium (TEA) incubations significantly inhibited the irisin-induced relaxation responses. In conclusion, the first physiological findings were obtained regarding the functional relaxing effects of irisin in rat thoracic aorta. The findings demonstrated that irisin induces relaxation responses in endothelium-intact and (or) endothelium-denuded aortic rings in a concentration-dependent manner. Furthermore, this study is the first to report that irisin-induced relaxation responses are related to the activity of the MEK1/2 pathway, KV channels, and calcium-activated K+ (SKCa and BKCa) channels.
      Citation: Canadian Journal of Physiology and Pharmacology
      PubDate: 2021-11-26T08:00:00Z
      DOI: 10.1139/cjpp-2021-0500
       
  • Transgenerational impact of topical steroid application on superoxide
           dismutase activities of hypothalamus-pituitary-adrenal axis in rats

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      Authors: Seher Polat, Armağan Caner
      Pages: 1 - 7
      Abstract: Canadian Journal of Physiology and Pharmacology, Ahead of Print.
      Topical steroids (TS) have been widely prescribed since the 1950s. This study investigated for the first time the transgenerational effects of TS on the antioxidant mechanism of the hypothalamus-pituitary-adrenal (HPA) axis, both in prenatal and infancy. Three generations (F1, F2, and F3) and prenatal group (P) were investigated in both sexes with two different time points; P45th and P75th day were accepted as puberty and early adulthood, respectively. Clobetasol propionate 0.05% was used as TS. Quantitative real-time PCR was performed to expressional analyses of Sod1, Sod2, and Sod3 genes in the HPA tissues. The Sod mRNA expression of the HPA belonging to P and F1 groups revealed similar results in both genders. The downregulation in the adrenal Sod level was determined in P and F1, F2, and F3 generations in both genders, especially in females (p < 0.05). The Sod activities in the pituitary of all groups were downregulated in female rats (p < 0.05). Interestingly, in male rats, Sod2 and Sod3 were not expressed in the pituitary compared with the control on the day P45, while Sod2 and Sod3 expressions were determined in all the groups on day P75. Sod1 overexpression was found in pituitary and hypothalamus of males in the F3 generation. This study showed that TS applied in infancy had a transgenerational adverse effect on antioxidant defense mechanisms, especially in the adrenal gland.
      Citation: Canadian Journal of Physiology and Pharmacology
      PubDate: 2021-11-26T08:00:00Z
      DOI: 10.1139/cjpp-2021-0493
       
  • Citral inhibits the nociception in the rat formalin test: effect of
           metformin and blockers of opioid receptor and the NO-cGMP-K+ channel
           pathway

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      Authors: Mario I. Ortiz, Raquel Cariño-Cortés, Víctor M. Muñoz-Pérez, Carlo Eduardo Medina-Solís, Gilberto Castañeda-Hernández
      Pages: 1 - 8
      Abstract: Canadian Journal of Physiology and Pharmacology, Ahead of Print.
      The objective of the present study was to scrutinize the effect of nitric oxide (NO), cyclic GMP (cGMP), potassium channel blockers, and metformin on the citral-produced peripheral antinociception. The rat paw 1% formalin test was used to assess nociception and antinociception. Rats were treated with local peripheral administration of citral (10–100 µg/paw). The antinociception of citral (100 µg/paw) was evaluated with and without the local pretreatment of naloxone, NG-L-nitro-arginine methyl ester (L-NAME, a NO synthesis inhibitor), 1H-(1,2,4)-oxadiazolo(4,2-a)quinoxalin-1-one (ODQ, a soluble guanylyl cyclase inhibitor), metformin, opioid receptors antagonists, and K+ channel blockers. Injection of citral in the rat paw significantly decreased the nociceptive effect of formalin administration during the two phases of the test. Local pretreatment of the paws with L-NAME and ODQ did not reduced the citral-induced antinociception. Glipizide or glibenclamide (Kir6.1-2; ATP-sensitive K+ channel blockers), tetraethylammonium or 4-aminopyridine (KV; voltage-gated K+ channel blockers), charybdotoxin (KCa1.1; big conductance calcium-activated K+ channel blocker), apamin (KCa2.1-3; small conductance Ca2+-activated K+ channel antagonist), or metformin, but not the opioid antagonists, reduced the antinociception of citral. Citral produced peripheral antinociception during both phases of the formalin test. These effects were due to the activation of K+ channels and a biguanide-dependent mechanism.
      Citation: Canadian Journal of Physiology and Pharmacology
      PubDate: 2021-11-26T08:00:00Z
      DOI: 10.1139/cjpp-2021-0458
       
  • PPARα/γ, adiponectin, and GLUT4 overexpression induced by moronic acid
           methyl ester influenced glucose and triglyceride levels of experimental
           diabetic mice

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      Authors: Samuel Estrada-Soto, Litzia Cerón-Romero, Gabriel Navarrete-Vázquez, Edgar Rosales-Ortega, Jaime Gómez-Zamudio, Miguel Cruz, Rafael Villalobos-Molina
      Pages: 1 - 11
      Abstract: Canadian Journal of Physiology and Pharmacology, Ahead of Print.
      The current study aimed to determine the antidiabetic and antidyslipidemic activities of moronic acid methyl ester (1) (compound 1) by in vivo, in vitro, in silico, and molecular biology studies. Compound 1 was evaluated to establish its dose-dependent antidiabetic and antihyperglycemic (50 mg/kg) activities, in diabetic and normoglycemic male CD1 mice, respectively. Also, compound 1 was subjected to a subacute study (50 mg/kg per day for 8 days) to determine blood biochemical profiles and the expression of protein tyrosine phosphatase 1B (PTP-1B), glucose transporter type 4 (GLUT4), peroxisome proliferator-activated receptor α (PPAR-α), PPAR-γ, adiponectin, interleukin-1β (IL-1β), and monocyte chemoattractant protein 1 (MCP-1) in adipose tissue of animals after treatment. Different doses in acute administration of compound 1 decreased glycemia (p < 0.05) compared with vehicle, showing greater effectiveness in the range 50–160 mg/kg. Also, the oral glucose tolerance test showed that compound 1 induced a significant antihyperglycemic action by opposing the hyperglycemic peak (p < 0.05). Moreover, compound 1 subacute administration decreased glucose and triglyceride levels after treatment (p < 0.05); while the expression of PPAR-α and PPAR-γ, adiponectin, and GLUT4 displayed an increase (p < 0.05) compared with the diabetic control group. In conclusion, compound 1 showed antihyperglycemic, antidiabetic, and antidyslipidemic effects in normal and diabetic mice, probably due to insulin sensitization through increased mRNA expression of GLUT4, PPAR-α, PPAR-γ, and adiponectin genes.
      Citation: Canadian Journal of Physiology and Pharmacology
      PubDate: 2021-11-10T08:00:00Z
      DOI: 10.1139/cjpp-2021-0526
       
  • Sirtuin 3 overexpression preserves maximal sarco(endo)plasmic reticulum
           calcium ATPase activity in the skeletal muscle of mice subjected to high
           fat – high sucrose feeding

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      Authors: Christopher J. Oldfield, Teri L. Moffatt, Vernon W. Dolinsky, Todd A. Duhamel
      Pages: 1 - 10
      Abstract: Canadian Journal of Physiology and Pharmacology, Ahead of Print.
      Sarco(endo)plasmic reticulum calcium (Ca2+) ATPase (SERCA) transports Ca2+ in muscle. Impaired SERCA activity may contribute to diabetic myopathy. Sirtuin (SIRT) 3 regulates muscle metabolism and function; however, it is unknown if SIRT3 regulates muscle SERCA activity or acetylation. We determined if SIRT3 overexpression enhances SERCA activity in mouse gastrocnemius muscle and if SIRT3 overexpression preserves gastrocnemius SERCA activity in a model of type 2 diabetes, induced by high fat – high sucrose (HFHS) feeding. We also determined if the acetylation status of SERCA proteins in mouse gastrocnemius is altered by SIRT3 overexpression or HFHS feeding. Wild-type (WT) and SIRT3 transgenic (SIRT3TG) mice, overexpressing SIRT3 in skeletal muscle, were fed a standard or HFHS diet for 4 months. SIRT3TG and WT mice developed obesity and glucose intolerance after 4 months of HFHS feeding. SERCA Vmax was higher in gastrocnemius of SIRT3TG mice compared with WT mice. HFHS-fed mice had lower SERCA1a protein levels and lower SERCA Vmax in their gastrocnemius than control-fed mice. The decrease in SERCA Vmax in gastrocnemius muscle due to HFHS feeding was attenuated by SIRT3 overexpression in HFHS-fed SIRT3TG mice. SERCA1a and SERCA2a acetylation in mouse gastrocnemius was not altered by genotype or diet. These findings suggest SIRT3 overexpression improves SERCA function in mouse skeletal muscle.
      Citation: Canadian Journal of Physiology and Pharmacology
      PubDate: 2021-10-25T07:00:00Z
      DOI: 10.1139/cjpp-2021-0587
       
  • Taurine alleviates kidney injury in a thioacetamide rat model by mediating
           Nrf2/HO-1, NQO-1, and MAPK/NF-κB signaling pathways

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      Authors: Amal M.H. Ghanim, Mahmoud R.T. Farag, Mahitab A. Anwar, Nada A.M. Ali, Mohammed A. Hawas, Hend M.E. Elsallab, Walaa A. Elhendawy, Lina A. Basyouni, Ola A. Refaey, Khaled E. Zaki, Noha A.M. Ali, Heba A. Metwaly
      Pages: 1 - 9
      Abstract: Canadian Journal of Physiology and Pharmacology, Ahead of Print.
      This study investigated the molecular mechanisms by which taurine exerts its reno-protective effects in thioacetamide (TAA) – induced kidney injury in rats. Rats received taurine (100 mg/kg daily, intraperitoneally) either from day 1 of TAA injection (250 mg/kg twice weekly for 6 weeks) or after 6 weeks of TAA administration. Taurine treatment, either concomitant or later as a therapy, restored kidney functions, reduced blood urea nitrogen (BUN), creatinine, and malondialdehyde (MDA), increased renal levels of superoxide dismutase (SOD), and reversed the increase of kidney injury molecule-1 (KIM-1) and neutrophil gelatinase–associated lipocalin (NGAL) caused by TAA. Taurine treatment also led to a significant rise in nuclear factor erythroid 2–related factor 2 (Nrf2), hemoxygenase-1 (HO-1), and NADPH quinone oxidoreductase-1 (NQO-1) levels, with significant suppression of extracellular signal-regulated kinase (ERK) 1/2, nuclear factor kappa B (NF-κB), and tumor necrosis factor α (TNF-α) gene expressions, and interleukin-18 (IL-18) and TNF-α protein levels compared with those in TAA kidney-injured rats. Taurine exhibited reno-protective potential in TAA-induced kidney injury through its antioxidant and anti-inflammatory effects. Taurine antioxidant activity is accredited for its effect on Nrf-2 induction and subsequent activation of HO-1 and NQO-1. In addition, taurine exerts its anti-inflammatory effect via regulating NF-κB transcription and subsequent production of pro-inflammatory mediators via mitogen-activated protein kinase (MAPK) signaling regulation.
      Citation: Canadian Journal of Physiology and Pharmacology
      PubDate: 2021-10-25T07:00:00Z
      DOI: 10.1139/cjpp-2021-0488
       
  • Gender-specific side effects of chemotherapy in pancreatic cancer patients

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      Authors: Silvia De Francia, Daniele Mancardi, Paola Berchialla, Tiziana Armando, Silvana Storto, Sarah Allegra, Giulia Soave, Silvia Racca, Francesco Chiara, Jennifer Carnovale, Libero Ciuffreda, Maria Valentina Mussa
      Pages: 1 - 7
      Abstract: Canadian Journal of Physiology and Pharmacology, Ahead of Print.
      Pancreatic carcinoma incidence showed a significant increase in men over the last few years and the prognosis remains poor. Patients are treated with different pharmacological plans with no evidence about gender-specific adverse effects. We aimed to investigate differences in the incidence of chemotherapy side effects in the treatment of pancreatic cancer, to provide insights toward a personalized assistance based in individual needs. The sample population is composed of 207 patients. Regression model highlighted the predictive role of female gender for alopecia, constipation, hand-foot syndrome, and epigastric pain. Also, considering single therapeutic schemes, gender differences have been reported. Moreover, evaluating the effect of age, a general reduced risk of toxicity has been reported in younger patients. To personalize chemotherapy and increase patient survival rate and life quality during the therapy, gender medicine and pharmacology studies are recommended.
      Citation: Canadian Journal of Physiology and Pharmacology
      PubDate: 2021-10-21T07:00:00Z
      DOI: 10.1139/cjpp-2021-0622
       
  • The OPG/RANKL/RANK system modulates calcification of common carotid artery
           in simulated microgravity rats by regulating NF-κB pathway

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      Authors: Huan Liu, Ning-Yu Ru, Yue Cai, Qiang Lyu, Chi-Hua Guo, Ying Zhou, Shao-Hua Li, Jiu-Hua Cheng, Jin-Rui Chang, Jin Ma, Xing-Li Su
      Pages: 1 - 10
      Abstract: Canadian Journal of Physiology and Pharmacology, Ahead of Print.
      Functional and structural adaptation of common carotid artery could be one of the important causes of postflight orthostatic intolerance after microgravity exposure, the mechanisms of which remain unclear. Recent evidence indicates that long-term spaceflight increases carotid artery stiffness, which might present a high risk to astronaut health and postflight working ability. Studies have suggested that vascular calcification is a common pathological change in cardiovascular diseases that is mainly manifested as an increase in vascular stiffness. Therefore, this study investigated whether simulated microgravity induces calcification of common carotid artery and to elucidate the underlying mechanisms. Four-week-old hindlimb-unweighted (HU) rats were used to simulate the deconditioning effects of microgravity on cardiovascular system. We found that simulated microgravity induced vascular smooth muscle cell (VSMC) osteogenic differentiation and medial calcification, increased receptor activator of nuclear factor κB (NF-κB) ligand (RANKL) and RANK expression, and enhanced NF-κB activation in rat common carotid artery. In vitro activation of the RANK pathway with exogenous RANKL, a RANK ligand, increased RANK and osteoprotegerin (OPG) expression in HU rats. Moreover, the expression of osteogenic markers and activation of NF-κB in HU rats were further enhanced by exogenous RANKL but suppressed by the RANK inhibitor osteoprotegerin fusion protein (OPG-Fc). These results indicated that the OPG/RANKL/RANK system modulates VSMC osteogenic differentiation and medial calcification of common carotid artery in simulated microgravity rats by regulating the NF-kB pathway.
      Citation: Canadian Journal of Physiology and Pharmacology
      PubDate: 2021-10-20T07:00:00Z
      DOI: 10.1139/cjpp-2021-0329
       
  • The protective effect of apelin-13 on cardiorenal toxicity induced by
           cyclophosphamide

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      Authors: Özden Kutlay, Arzu Keskin Aktan, Esra Aslan
      Pages: 1 - 10
      Abstract: Canadian Journal of Physiology and Pharmacology, Ahead of Print.
      Cyclophosphamide is a chemotherapeutic drug that is widely used in the clinic and can cause multi-organ toxicity. Apelin-13 is an endogenous adipocytokine with antioxidant properties. Therefore, this study investigated the possibility of apelin-13 being a potential therapeutic agent on cardiac toxicity and nephrotoxicity caused by cyclophosphamide. In this study, a total of four groups were formed with eight rats in each group. Group I: the control group was administered only saline (i.p.). Group II: cyclophosphamide, a single dose of 200 mg/kg (i.p.) on day 7. Group III: apelin-13 (15 μg/kg), for 7 days (i.p.). Group IV: administered apelin-13 (15 μg/kg) (i.p.) for 7 days and a single dose of cyclophosphamide (200 mg/kg) (i.p.) on day 7, the rats were sacrificed on day 8. Lactate dehydrogenase, cardiac troponin I (cTnI), creatine kinase MB (CK-MB), aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), malondialdehyde, creatinine, and blood urea nitrogen were found to be high in the cyclophosphamide group; however, these values were reduced with apelin-13 administration. Antioxidant enzymes such as superoxide dismutase (SOD), glutathione peroxidase (GPx), catalase, and reduced glutathione (GSH) decreased in the cyclophosphamide group, and apelin-13 increased these enzyme activities. In addition, histopathological examinations also supported the results obtained. The findings of this study showed that apelin-13 has a protective effect against cardiorenal toxicity caused by cyclophosphamide.
      Citation: Canadian Journal of Physiology and Pharmacology
      PubDate: 2021-10-19T07:00:00Z
      DOI: 10.1139/cjpp-2021-0337
       
  • Dexamethasone attenuates the modulatory effect of the insular cortex on
           the baroreflex in anesthetized rat

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      Authors: Tatiana S. Tumanova, Tatiana N. Kokurina, Galina I. Rybakova, Viacheslav G. Aleksandrov
      Pages: 1 - 7
      Abstract: Canadian Journal of Physiology and Pharmacology, Ahead of Print.
      The arterial baroreflex (BR) is an important neural mechanism for the stabilization of arterial pressure (AP). It is known that the insular cortex (IC) and other parts of the central autonomic network (CAN) are able to modulate the BR arc, altering baroreflex sensitivity (BRS). In addition, the sensitivity of the BR changes under the influence of hormones, in particular glucocorticoids (GCs). It has been suggested that GCs may influence BRS by altering the ability of the IC to modulate the BR. This hypothesis has been tested in experiments on rats anesthetized with urethane. It was found that microelectrostimulation of the visceral area in the left IC causes a short-term drop in AP, which is accompanied by bradycardia and impairs BRS. The synthetic GC dexamethasone (DEX) did not significantly affect the magnitude of depressor responses but increased BRS and impaired the effect of IC stimulation on the BR. The results obtained confirm the hypothesis put forward and suggest that GC can attenuate the inhibitory effects of the IC on the BR arc, thereby enhancing the sensitivity of the BR.
      Citation: Canadian Journal of Physiology and Pharmacology
      PubDate: 2021-10-13T07:00:00Z
      DOI: 10.1139/cjpp-2021-0385
       
 
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