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  Subjects -> PHARMACY AND PHARMACOLOGY (Total: 575 journals)
Showing 1 - 200 of 253 Journals sorted by number of followers
Nature Reviews Drug Discovery     Full-text available via subscription   (Followers: 324)
International Journal of Drug Policy     Hybrid Journal   (Followers: 254)
Journal of Clinical Oncology     Hybrid Journal   (Followers: 239)
Journal of Medicinal Chemistry     Hybrid Journal   (Followers: 154)
Journal of Pharmaceutical Sciences     Hybrid Journal   (Followers: 151)
Drugs     Full-text available via subscription   (Followers: 143)
Advanced Drug Delivery Reviews     Hybrid Journal   (Followers: 94)
Pharmaceutical Research     Hybrid Journal   (Followers: 93)
European Journal of Pharmaceutical Sciences     Hybrid Journal   (Followers: 85)
Drug Safety     Full-text available via subscription   (Followers: 81)
Annals of Pharmacotherapy     Hybrid Journal   (Followers: 56)
Biomaterials     Hybrid Journal   (Followers: 55)
Clinical Pharmacology & Therapeutics     Hybrid Journal   (Followers: 45)
Regulatory Toxicology and Pharmacology     Hybrid Journal   (Followers: 41)
Annual Review of Pharmacology and Toxicology     Full-text available via subscription   (Followers: 38)
Journal of Controlled Release     Hybrid Journal   (Followers: 37)
International Journal of Pharmaceutics     Hybrid Journal   (Followers: 37)
Clinical Therapeutics     Hybrid Journal   (Followers: 34)
European Journal of Pharmaceutics and Biopharmaceutics     Hybrid Journal   (Followers: 34)
Pharmacoepidemiology and Drug Safety     Hybrid Journal   (Followers: 33)
British Journal of Clinical Pharmacology     Hybrid Journal   (Followers: 31)
Journal of Pharmacy and Pharmacology     Full-text available via subscription   (Followers: 31)
Drug Development and Industrial Pharmacy     Hybrid Journal   (Followers: 29)
Clinical Pharmacokinetics     Full-text available via subscription   (Followers: 28)
PharmacoEconomics     Full-text available via subscription   (Followers: 26)
Critical Reviews in Toxicology     Hybrid Journal   (Followers: 25)
AAPS Journal     Hybrid Journal   (Followers: 25)
Journal of Clinical Psychopharmacology     Hybrid Journal   (Followers: 24)
International Journal of Pharmacy Practice     Full-text available via subscription   (Followers: 24)
Toxicology and Applied Pharmacology     Hybrid Journal   (Followers: 24)
Chemical Research in Toxicology     Hybrid Journal   (Followers: 22)
Journal of Pharmacokinetics and Pharmacodynamics     Hybrid Journal   (Followers: 22)
Journal of Pain & Palliative Care Pharmacotherapy     Hybrid Journal   (Followers: 21)
Trends in Pharmacological Sciences     Full-text available via subscription   (Followers: 20)
Journal of Clinical Pharmacology     Hybrid Journal   (Followers: 20)
Journal of Applied Toxicology     Hybrid Journal   (Followers: 19)
Pharmaceutical Development and Technology     Hybrid Journal   (Followers: 19)
American Journal of Cardiovascular Drugs     Hybrid Journal   (Followers: 19)
Clinical Trials     Hybrid Journal   (Followers: 18)
Toxicology     Hybrid Journal   (Followers: 18)
Journal of Pharmaceutical and Biomedical Analysis     Hybrid Journal   (Followers: 18)
Clinical Toxicology     Hybrid Journal   (Followers: 18)
International Journal of Toxicology     Hybrid Journal   (Followers: 17)
Journal of Clinical Pharmacy and Therapeutics     Hybrid Journal   (Followers: 17)
Critical Reviews in Clinical Laboratory Sciences     Hybrid Journal   (Followers: 16)
Journal of Natural Products     Hybrid Journal   (Followers: 16)
Pharmaceutical Statistics     Hybrid Journal   (Followers: 15)
Toxicology Letters     Hybrid Journal   (Followers: 15)
Journal of Pharmacy Practice     Hybrid Journal   (Followers: 15)
Psychopharmacology     Hybrid Journal   (Followers: 15)
Basic & Clinical Pharmacology & Toxicology     Hybrid Journal   (Followers: 14)
Cardiovascular Drugs and Therapy     Hybrid Journal   (Followers: 14)
European Journal of Clinical Pharmacology     Hybrid Journal   (Followers: 14)
Current Medicinal Chemistry     Hybrid Journal   (Followers: 13)
American Journal of Therapeutics     Hybrid Journal   (Followers: 13)
Drug and Chemical Toxicology     Hybrid Journal   (Followers: 13)
Journal of the American Pharmacists Association     Full-text available via subscription   (Followers: 13)
Drug Metabolism and Disposition     Hybrid Journal   (Followers: 13)
Clinical Research and Regulatory Affairs     Hybrid Journal   (Followers: 12)
Drug Discovery Today: Technologies     Full-text available via subscription   (Followers: 12)
Seminars in Hematology     Hybrid Journal   (Followers: 12)
Journal of Oncology Pharmacy Practice     Hybrid Journal   (Followers: 12)
Journal of Psychopharmacology     Hybrid Journal   (Followers: 11)
Biopharmaceutics and Drug Disposition     Hybrid Journal   (Followers: 11)
Current Pharmaceutical Design     Hybrid Journal   (Followers: 11)
Drug Development Research     Hybrid Journal   (Followers: 11)
Toxicology in Vitro     Hybrid Journal   (Followers: 11)
Seminars in Oncology Nursing     Full-text available via subscription   (Followers: 10)
Biochemical Pharmacology     Hybrid Journal   (Followers: 10)
Journal of Pharmacology and Experimental Therapeutics     Hybrid Journal   (Followers: 10)
Journal of Separation Science     Hybrid Journal   (Followers: 10)
CNS Drugs     Full-text available via subscription   (Followers: 10)
Current Pharmaceutical Biotechnology     Hybrid Journal   (Followers: 10)
Journal of Medical Marketing     Hybrid Journal   (Followers: 10)
Drugs & Aging     Full-text available via subscription   (Followers: 10)
European Neuropsychopharmacology     Hybrid Journal   (Followers: 9)
Food Additives & Contaminants Part A     Hybrid Journal   (Followers: 9)
Environmental Toxicology and Pharmacology     Hybrid Journal   (Followers: 9)
Medicinal Chemistry     Hybrid Journal   (Followers: 9)
Biometrical Journal     Hybrid Journal   (Followers: 9)
Drugs & Therapy Perspectives     Full-text available via subscription   (Followers: 9)
Prescriber     Hybrid Journal   (Followers: 9)
ChemMedChem     Hybrid Journal   (Followers: 9)
Current Opinion in Pharmacology     Hybrid Journal   (Followers: 9)
European Journal of Pharmacology     Hybrid Journal   (Followers: 8)
Clinical Drug Investigation     Full-text available via subscription   (Followers: 8)
Inhalation Toxicology     Hybrid Journal   (Followers: 8)
Antiviral Research     Hybrid Journal   (Followers: 8)
Drug Metabolism Reviews     Hybrid Journal   (Followers: 8)
Progress in Neuro-Psychopharmacology and Biological Psychiatry     Hybrid Journal   (Followers: 8)
Human & Experimental Toxicology     Hybrid Journal   (Followers: 8)
Drug Delivery     Open Access   (Followers: 8)
BioDrugs     Full-text available via subscription   (Followers: 8)
Frontiers in Drug Design & Discovery     Hybrid Journal   (Followers: 8)
Expert Review of Pharmacoeconomics & Outcomes Research     Full-text available via subscription   (Followers: 8)
Experimental and Clinical Psychopharmacology     Full-text available via subscription   (Followers: 7)
Toxicology Mechanisms and Methods     Hybrid Journal   (Followers: 7)
Journal of Pharmacological and Toxicological Methods     Hybrid Journal   (Followers: 7)
Clinical and Experimental Pharmacology and Physiology     Hybrid Journal   (Followers: 7)
Scandinavian Journal of Clinical and Laboratory Investigation     Hybrid Journal   (Followers: 7)
Epilepsy Research     Hybrid Journal   (Followers: 7)
Toxicology and Industrial Health     Hybrid Journal   (Followers: 6)
Journal of Veterinary Pharmacology and Therapeutics     Hybrid Journal   (Followers: 6)
Skin Pharmacology and Physiology     Full-text available via subscription   (Followers: 6)
Journal of Cardiovascular Pharmacology     Hybrid Journal   (Followers: 6)
AAPS PharmSciTech     Hybrid Journal   (Followers: 6)
Current Drug Discovery Technologies     Hybrid Journal   (Followers: 6)
Current Drug Delivery     Hybrid Journal   (Followers: 6)
Current Therapeutic Research     Open Access   (Followers: 6)
Expert Review of Cardiovascular Therapy     Full-text available via subscription   (Followers: 6)
Neuropharmacology     Hybrid Journal   (Followers: 5)
Current Drug Metabolism     Hybrid Journal   (Followers: 5)
Fitoterapia     Hybrid Journal   (Followers: 5)
Expert Review of Molecular Diagnostics     Full-text available via subscription   (Followers: 5)
Expert Review of Anti-infective Therapy     Full-text available via subscription   (Followers: 5)
Anti-Infective Agents     Hybrid Journal   (Followers: 5)
Toxicon     Hybrid Journal   (Followers: 5)
Medicinal Research Reviews     Hybrid Journal   (Followers: 5)
Investigational New Drugs     Hybrid Journal   (Followers: 5)
Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry     Hybrid Journal   (Followers: 5)
Current Cancer Therapy Reviews     Hybrid Journal   (Followers: 5)
Reviews of Physiology, Biochemistry and Pharmacology     Hybrid Journal   (Followers: 4)
Planta Medica     Hybrid Journal   (Followers: 4)
Current Vascular Pharmacology     Hybrid Journal   (Followers: 4)
Pharmaceutical Medicine     Full-text available via subscription   (Followers: 4)
Journal of Child and Adolescent Psychopharmacology     Hybrid Journal   (Followers: 4)
CNS Drug Reviews     Open Access   (Followers: 4)
Inpharma Weekly     Full-text available via subscription   (Followers: 4)
Journal of Labelled Compounds and Radiopharmaceuticals     Hybrid Journal   (Followers: 4)
Immunopharmacology and Immunotoxicology     Hybrid Journal   (Followers: 4)
International Journal of Pharmaceutical and Healthcare Marketing     Hybrid Journal   (Followers: 4)
Inflammation Research     Hybrid Journal   (Followers: 4)
Cancer Chemotherapy and Pharmacology     Hybrid Journal   (Followers: 4)
International Journal of Neuropsychopharmacology     Open Access   (Followers: 3)
Pharmacology & Therapeutics     Hybrid Journal   (Followers: 3)
Physiology International     Full-text available via subscription   (Followers: 3)
Cardiovascular Therapeutics     Open Access   (Followers: 3)
ASSAY and Drug Development Technologies     Hybrid Journal   (Followers: 3)
Pharmacopsychiatry     Hybrid Journal   (Followers: 3)
Chemotherapy     Full-text available via subscription   (Followers: 3)
Therapeutic Drug Monitoring     Hybrid Journal   (Followers: 3)
Current Drug Therapy     Hybrid Journal   (Followers: 3)
Research in Social and Administrative Pharmacy     Hybrid Journal   (Followers: 3)
PharmacoEconomics & Outcomes News     Full-text available via subscription   (Followers: 3)
Journal of Aerosol Medicine and Pulmonary Drug Delivery     Hybrid Journal   (Followers: 3)
Journal of Ethnopharmacology     Hybrid Journal   (Followers: 3)
Drug Resistance Updates     Hybrid Journal   (Followers: 3)
Journal of Infection and Chemotherapy     Hybrid Journal   (Followers: 3)
Journal of Cardiovascular Pharmacology and Therapeutics     Hybrid Journal   (Followers: 3)
Current Pharmacogenomics and Personalized Medicine     Hybrid Journal   (Followers: 3)
Acta Pharmacologica Sinica     Hybrid Journal   (Followers: 3)
Microbial Drug Resistance     Hybrid Journal   (Followers: 3)
Frontiers in Medicinal Chemistry     Hybrid Journal   (Followers: 3)
Human Psychopharmacology Clinical and Experimental     Hybrid Journal   (Followers: 3)
Journal of Pain Management & Medicine     Open Access   (Followers: 2)
BMC Pharmacology     Open Access   (Followers: 2)
The Brown University Psychopharmacology Update     Hybrid Journal   (Followers: 2)
International Clinical Psychopharmacology     Hybrid Journal   (Followers: 2)
Canadian Journal of Physiology and Pharmacology     Hybrid Journal   (Followers: 2)
Journal of Drug Targeting     Hybrid Journal   (Followers: 2)
Inflammopharmacology     Hybrid Journal   (Followers: 2)
Journal of Inflammation     Open Access   (Followers: 2)
Fundamental & Clinical Pharmacology     Hybrid Journal   (Followers: 2)
Behavioural Pharmacology     Hybrid Journal   (Followers: 2)
Vascular Pharmacology     Hybrid Journal   (Followers: 2)
Pulmonary Pharmacology & Therapeutics     Hybrid Journal   (Followers: 2)
Biomedicine & Pharmacotherapy     Full-text available via subscription   (Followers: 2)
Clinical Neuropharmacology     Hybrid Journal   (Followers: 2)
Drugs in R & D     Full-text available via subscription   (Followers: 2)
International Immunopharmacology     Hybrid Journal   (Followers: 2)
Pharmacology Biochemistry and Behavior     Hybrid Journal   (Followers: 2)
Letters in Drug Design & Discovery     Hybrid Journal   (Followers: 2)
Archiv der Pharmazie     Hybrid Journal   (Followers: 2)
Pharmacological Reviews     Hybrid Journal   (Followers: 2)
Molecular Pharmacology     Hybrid Journal   (Followers: 2)
Journal of Microencapsulation: Microcapsules, Liposomes, Nanoparticles, Microcells, Microspheres     Hybrid Journal   (Followers: 2)
Toxicological & Environmental Chemistry     Hybrid Journal   (Followers: 2)
Particulate Science and Technology: An International Journal     Hybrid Journal   (Followers: 1)
Pharmacological Research     Hybrid Journal   (Followers: 1)
Current Enzyme Inhibition     Hybrid Journal   (Followers: 1)
Journal of Neuroimmune Pharmacology     Hybrid Journal   (Followers: 1)
Current Pharmaceutical Analysis     Hybrid Journal   (Followers: 1)
Current Neuropharmacology     Hybrid Journal   (Followers: 1)
Pharmacogenetics and Genomics     Hybrid Journal   (Followers: 1)
Journal of Texture Studies     Hybrid Journal   (Followers: 1)
Pharmaceutical Biology     Open Access  
Journal of Liposome Research     Hybrid Journal  
Toxin Reviews     Hybrid Journal  
Kaohsiung Journal of Medical Sciences     Open Access  
Redox Report     Open Access  
Pharmacology     Full-text available via subscription  
Pharmaceutical Chemistry Journal     Hybrid Journal  
NeuroMolecular Medicine     Hybrid Journal  
Journal of Ocular Pharmacology and Therapeutics     Hybrid Journal  
Harm Reduction Journal     Open Access  
Current Nanoscience     Hybrid Journal  
Infectious Disorders - Drug Targets     Hybrid Journal  
Current Bioactive Compounds     Hybrid Journal  
Cancer Biotherapy & Radiopharmaceuticals     Hybrid Journal  
Autonomic & Autacoid Pharmacology     Hybrid Journal  

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Naunyn-Schmiedeberg's Archives of Pharmacology
Journal Prestige (SJR): 0.836
Citation Impact (citeScore): 2
Number of Followers: 0  
 
  Hybrid Journal Hybrid journal (It can contain Open Access articles)
ISSN (Print) 0028-1298 - ISSN (Online) 1432-1912
Published by Springer-Verlag Homepage  [2469 journals]
  • Pandemic COVID-19, an update of current status and new therapeutic
           strategies

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      Abstract: The global COVID-19 pandemic is underway. In recent weeks, several countries throughout the globe, and particularly in Europe, have experienced an exponential increase in the number of individuals infected with COVID-19, probably induced by a new variant of SARS-CoV-2, called the “Omicron variant.” Mass vaccination against COVID-19 continues worldwide. Are authorized mRNA vaccines effective against the new Omicron variant? Recently, several pharmaceutical companies have developed oral antiviral pills against SARS-CoV-2, i.e., molnupiravir and paxlovid, that inhibit SARS-CoV-2 viral replication by acting on the RNA polymerase of SARS-CoV. In pre-registration clinical trials, molnupiravir and paxlovid have shown excellent clinical efficacy results, but what impact will these new oral antiviral agents have against pandemic COVID-19? In what specific clinical situations are they preferred over other antivirals such as remdesivir? In this brief review, we explore these important aspects. Graphical abstract
      PubDate: 2022-10-01
       
  • Drug repurposing—an emerging strategy in cancer therapeutics

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      Abstract: Abstract Cancer is a complex disease affecting millions of people around the world. Despite advances in surgical and radiation therapy, chemotherapy continues to be an important therapeutic option for the treatment of cancer. The current treatment is expensive and has several side effects. Also, over time, cancer cells develop resistance to chemotherapy, due to which there is a demand for new drugs. Drug repurposing is a novel approach that focuses on finding new applications for the old clinically approved drugs. Current advances in the high-dimensional multiomics landscape, especially proteomics, genomics, and computational omics-data analysis, have facilitated drug repurposing. The drug repurposing approach provides cheaper, effective, and safe drugs with fewer side effects and fastens the process of drug development. The review further delineates each repurposed drug’s original indication and mechanism of action in cancer. Along with this, the article also provides insight upon artificial intelligence and its application in drug repurposing. Clinical trials are vital for determining medication safety and effectiveness, and hence the clinical studies for each repurposed medicine in cancer, including their stages, status, and National Clinical Trial (NCT) identification, are reported in this review article. Various emerging evidences imply that repurposing drugs is critical for the faster and more affordable discovery of anti-cancerous drugs, and the advent of artificial intelligence-based computational tools can accelerate the translational cancer-targeting pipeline.
      PubDate: 2022-10-01
       
  • β1- and β1/β2-adrenergic receptor antagonists block
           6-nitrodopamine-induced contractions of the rat isolated epididymal vas
           deferens

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      Abstract: Abstract 6-Nitrodopamine (6-ND) is an endogenous modulator of the contractility in the rat isolated epididymal vas deferens (RIEVD) and considered to be the main peripheral mediator of the emission process. Use of selective and unselective β-adrenergic receptor antagonists has been associated with ejaculatory failure. Here, the effects of selective β1- and β1/β2-adrenergic receptor antagonists on RIEVD contractions induced by 6-ND, dopamine, noradrenaline, adrenaline, and electric-field stimulation (EFS) were investigated. The selective β1-adrenergic receptor antagonists atenolol (0.1 and 1 µM), betaxolol (1 µM), and metoprolol (1 µM) and the unselective β1/β2-adrenergic receptor antagonists propranolol (1 and 10 µM) and pindolol (10 µM) caused significant rightward shifts of the concentration–response curve to 6-ND (pA2 6.41, 6.91, 6.75, 6.47, and 5.74; for atenolol, betaxolol, metoprolol, propranolol, and pindolol), but had no effect on dopamine-, noradrenaline-, and adrenaline-induced contractions. The effects of selective β1- and β1/β2-adrenergic receptor antagonists at a higher concentration (atenolol 1 µM, betaxolol 1 µM, metoprolol 1 µM, propranolol 10 µM, and pindolol 10 µM) also reduced the EFS-induced RIEVD contractions in control, but not in RIEVD obtained from L-NAME-treated animals. The selective β1-adrenoceptor agonist RO-363, the selective β2-adrenoceptor agonist salbutamol, and the selective β3-adrenoceptor agonist mirabegron, up to 300 µM, had no effect on the RIEVD tone. The results demonstrate that β1- and β1-/β2-adrenoceptor receptor antagonists act as 6-ND receptor antagonists in RIEVD, further confirming the main role of 6-ND in the RIEVD contractility.
      PubDate: 2022-10-01
       
  • Luteolin-7-O-rutinoside from Pteris cretica L. var. nervosa attenuates
           LPS/D-gal-induced acute liver injury by inhibiting PI3K/AKT/AMPK/NF-κB
           signaling pathway

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      Abstract: Pteris cretica L. var. nervosa is one of the most well-known Chinese medicines. Although it is widely used to treat jaundice hepatitis, the main ingredient for its treatment was not thoroughly explored until recently. Essentially, the purpose of this study is to find the monomer compound in Pteris cretica L. var. nervosa, which is most likely to be effective in treating liver injury. Through the model of LPS/D-gal-induced liver injury in mice, the best therapeutic site of the total extract was explored, the chemical components of the parts with the best therapeutic effect were separated, a total of 10 flavonoids were isolated, and the RAW264.7 cells induced by LPS were used as the experimental model to explore the preliminary anti-inflammatory activity of NO production in vitro. Finally, the anti-inflammatory activity and the highest content in this plant Luteolin-7-O-rutinoside (LUT) were selected, as the object of study in vivo. It was found that LUT could not only reduce alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels, but also significantly reduce the release of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and interleukin-1β (IL-1β), and inhibit PI3K/AKT/AMPK/NF-κB pathway. In addition, LUT can increase levels of SOD and GSH to reduce oxidative stress. It has an obvious therapeutic effect on acute liver injury induced by LPS/D-gal in mice. Therefore, infer LUT is a functional substance in Pteris cretica L. var. nervosa. Graphical abstract
      PubDate: 2022-10-01
       
  • Evaluation of rosmarinic acid against myocardial infarction in maternally
           separated rats

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      Abstract:   Depression and coronary heart diseases are the common comorbid disorder affecting humans globally. The present study evaluated the effectiveness of rosmarinic acid (RA) against myocardial infarction (MI) in comorbid depression induced by maternal separation in rats. Maternal stress is one of the childhood crises that may be a potential risk factor for coronary heart disease in later part of life. As per protocol, 70–80% of pups were separated daily for 3 h between postnatal day 1 (PND1) and postnatal day 21 (PND21). Forced-swim test, sucrose preference test, and electrocardiography were performed during the experiment. Body weight was measured on PND0, PND35, and PND55. Orally rosmarinic acid (25 mg/kg and 50 mg/kg) and fluoxetine (10 mg/kg) was done from PND35 to PND55. On PND53 and PND54, isoproterenol (100 mg/kg, subcutaneously) was administered to induce myocardial infarction. On PND55, blood was collected and animals sacrificed, and plasma corticosterone, brain-derived neurotrophic factor, cardiac biomarkers, interleukine-10, and anti-oxidant parameters were measured. Rosmarinic acid and fluoxetine ameliorated the maternal separation–induced increase in immobility period, anhedonia, body weight, ST elevation, corticosterone, creatine kinase-MB (CK-MB), and lactate dehydrogenase (LDH). At the same time, both drugs elevated the tissue levels of BDNF, IL-10, glutathione, and superoxide dismutase activity. This study provides the first experimental evidence that maternal stress is an independent risk factor of cardiac abnormalities in rats. Moreover, maternal stress synergistically increases the severity of cardiac abnormalities induced by isoproterenol. Interestingly, fluoxetine and rosmarinic acid effectively ameliorated behavioral anomalies and myocardial infarction in maternally separated rats. Graphical abstract  Schematic representation of possible molecular mechanism of action of rosmarinic acid against MS-induced myocardial infarction. RA, rosmarinic acid; MS, maternal separation; PND, postnatal days; ISO, isoproterenol; BDNF, brain-derived neurotrophic factor; GSH, glutathione; SOD, superoxide dismutase; IL-10, interleukin-10; MI, myocardial infarction
      PubDate: 2022-10-01
       
  • [1,2,4] Triazolo [3,4-a]isoquinoline chalcone derivative exhibits
           anticancer activity via induction of oxidative stress, DNA damage, and
           apoptosis in Ehrlich solid carcinoma-bearing mice

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      Abstract: Abstract Despite the advances made in cancer therapeutics, their adverse effects remain a major concern, putting safer therapeutic options in high demand. Since chalcones, a group of flavonoids and isoflavonoids, act as promising anticancer agents, we aimed to evaluate the in vivo anticancer activity of a synthetic isoquinoline chalcone (CHE) in a mice model with Ehrlich solid carcinoma. Our in vivo pilot experiments revealed that the maximum tolerated body weight-adjusted CHE dose was 428 mg/kg. Female BALB/c mice were inoculated with Ehrlich ascites carcinoma cells and randomly assigned to three different CHE doses administered intraperitoneally (IP; 107, 214, and 321 mg/kg) twice a week for two consecutive weeks. A group injected with doxorubicin (DOX; 4 mg/kg IP) was used as a positive control. We found that in CHE-treated groups: (1) tumor weight was significantly decreased; (2) the total antioxidant concentration was substantially depleted in tumor tissues, resulting in elevated oxidative stress and DNA damage evidenced through DNA fragmentation and comet assays; (3) pro-apoptotic genes p53 and Bax, assessed via qPCR, were significantly upregulated. Interestingly, CHE treatment reduced immunohistochemical staining of the proliferative marker ki67, whereas BAX was increased. Notably, histopathological examination indicated that unlike DOX, CHE treatment had minimal toxicity on the liver and kidney. In conclusion, CHE exerts antitumor activity via induction of oxidative stress and DNA damage that lead to apoptosis, making CHE a promising candidate for solid tumor therapy.
      PubDate: 2022-10-01
       
  • Exploration of the amino acid metabolic signature in anthracycline-induced
           cardiotoxicity using an optimized targeted metabolomics approach based on
           UPLC-MS/MS

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      Abstract: Abstract Although anthracyclines improve the long-term survival rate of patients with cancer, severe and irreversible myocardial damage limits their clinical application. Amino acid (AA) metabolism in cardiomyocytes can be altered under pathological conditions. Therefore, exploring the AA metabolic signature in anthracycline-induced cardiotoxicity (AIC) is important for identifying novel mechanisms. We established mouse and cellular models of Adriamycin (ADR)-induced cardiac injury. We observed a decreased expression of troponins I (cTnI) after ADR treatment and ADR accelerated the degradation of cTnI, implying that AA metabolism could be altered in AIC. Using a targeted AA metabolomics approach based on ultra-performance liquid chromatography–tandem mass spectrometry (UPLC-MS/MS), the AA metabolic signatures in the sera of AIC mice and supernatant samples of ADR-treated H9c2 cardiomyocytes were analyzed. The levels of 14 AA metabolites were altered in ADR-treated mice (p < 0.05). Via bioinformatics analysis, we identified nine differential AA metabolites in mice and five differential AA metabolites in ADR-treated H9c2 cardiomyocytes. Three AAs with increased levels (l-glutamate, l-serine, and l-tyrosine) overlapped in the two models, suggesting a possible mechanism of AA metabolic impairment during AIC. The metabolic pathways perturbed by AIC involved aminoacyl-tRNA biosynthesis and alanine, aspartate, and glutamate metabolism. Our data suggests that ADR perturbed AA metabolism in AIC models. Moreover, the targeted AA metabolomics approach based on UPLC-MS/MS can be a unique platform to provide new clues for the prevention and treatment of AIC.
      PubDate: 2022-10-01
       
  • Peripheral tissular analysis of rapamycin’s effect as a
           neuroprotective agent in vivo

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      Abstract: Rapamycin is the best-characterized autophagy inducer, which is related to its antiaging and neuroprotective effects. Although rapamycin is an FDA-approved drug for human use in organ transplantation and cancer therapy, its administration as an antiaging and neuroprotective agent is still controversial because of its immunosuppressive and reported side effects. Therefore, it is critical to determine whether the dose that exerts a neuroprotective effect, 35 times lower than that used as an immunosuppressant agent, harms peripheral organs. We validated the rapamycin neuroprotective dosage in a Parkinsonʼs disease (PD) model induced with paraquat. C57BL/6 J mice were treated with intraperitoneal (IP) rapamycin (1 mg/kg) three times per week, followed by paraquat (10 mg/kg) twice per week for 6 weeks, along with rapamycin on alternate days. Rapamycin significantly decreased dopaminergic neuronal loss induced by paraquat. Since rapamycin’s neuroprotective effect in a PD model was observed at 7 weeks of treatment; we evaluated its effect on the liver, kidney, pancreas, and spleen. In addition, we prolonged treatment with rapamycin for 14 weeks. Tissue sections were subjected to histochemical, immunodetection, and morphometric analysis. Chronic rapamycin administration does not affect bodyweight, survival, and liver or kidney morphology. Although the pancreas tissular architecture and cellular distribution in Langerhans islets are modified, they may be reversible. The spleen B lymphocyte and macrophage populations were decreased. Notably, the lymphocyte T population was not affected. Therefore, chronic administration of a rapamycin neuroprotective dose does not produce significant tissular alterations. Our findings support the therapeutic potential of rapamycin as a neuroprotective agent. Graphical abstract
      PubDate: 2022-10-01
       
  • Resolvin D5 disrupts anxious- and depressive-like behaviors in a type 1
           diabetes mellitus animal model

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      Abstract: Abstract Type 1 diabetes mellitus (T1DM) is a chronic disease related to a persistent inflammatory process reaching the central nervous system, which leads to psychiatric comorbidities such as depression and anxiety. The search for new therapeutic agents effective in alleviating the psychiatric condition associated with T1DM becomes critical. Using an animal model of T1DM, we aimed to evaluate the effect of a specific specialized pro-resolving lipid mediator Resolvin D5 (RvD5), in preventing behaviors related to depression and anxiety, investigating its influence on inflammasome in interleukin (IL)-1β in the hippocampus and prefrontal cortex. After experimental T1DM induction with streptozotocin (60 mg/kg, i.p.), these animals were treated for 23 days and randomly divided into 6 subgroups according to the treatment: vehicle (VEH), the antidepressant Fluoxetine (FLX; 10 mg/kg), the nonsteroidal anti-inflammatory Ibuprofen (IBU; 30 mg/kg) or Resolvin D5 (RvD5; 1 3, or 10 ng/animal). As a control group for the experimental-T1DM condition, a group of normoglycemic animals treated with VEH underwent the same behavioral tests: elevated plus maze, open field, and modified forced swimming tests. In the end, hippocampus and prefrontal cortex samples were processed to analyze the pro-inflammatory cytokine IL-1β levels. Our data showed that RvD5 treatment prevented the more pronounced anxious-like and reduced the depressive-like behaviors of experimental-T1DM animals and significantly improved the plasma glucose levels. Additionally, RvD5 treatment prevented the increased level of pro-inflammatory cytokine IL-1β in the hippocampus and prefrontal cortex of experimental-T1DM rats. To conclude, RvD5 presents a preventive therapeutic potential in impairing the development of the emotional complications resulting from T1DM. This potential may be related to its protective profile, as demonstrated in this study by its pro-resolutive action on neuroinflammation in the hippocampus and prefrontal cortex.
      PubDate: 2022-10-01
       
  • Ameliorative effect of two structurally divergent hydrazide derivatives
           against DSS-induced colitis by targeting Nrf2 and NF-κB signaling in mice
           

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      Abstract: Abstract The environmental factors and genetic vulnerability trigger the inflammatory bowel diseases (IBDs) such as ulcerative colitis and Crohn’s disease. Furthermore, the oxidative stress and inflammatory cytokines have been implicated in the aggravation of the IBDs. The aim of the present study was to investigate the effect of N-(benzylidene)-2-((2-hydroxynaphthalen-1-yl)diazenyl)benzohydrazides (NCHDH and NTHDH) compounds against the DSS-induced colitis in mice. The colitis was induced by 5% dextran sulfate sodium (DSS) dissolved in normal saline for 5 days. The effect of the NCHDH and NTHDH on the behavioral, biochemical, histological, and immunohistological parameters was assessed. The NCHDH and NTHDH treatment improved the behavioral parameters such as food intake, disease activity index, and diarrhea score significantly compared to DSS control. The NCHDH and NTHDH treatments significantly increased the antioxidant enzymes, whereas oxidative stress markers were markedly reduced. Similarly, the NCHDH and NTHDH treatments significantly suppressed the activity of nitric oxide (NO), myeloperoxidase (MPO), and eosinophil peroxidase (EPO). The histological studies showed a significant reduction in inflammation, immune cell infiltration, and fibrosis in the NCHDH- and NTHDH-treated groups. The immunohistochemical results demonstrated that NCHDH and NTHDH treatments markedly increase the expression level of Nrf2, HO-1 (hemeoxygenase-1), TRX (thioredoxin reductase), and IκB compared to the DSS-induced group. In the same way, the NCHDH and NTHDH significantly reduced the NF-κB and COX-2 (cyclooxygenase-2) expression levels. The NCHDH and NTHDH treatment significantly improved the symptoms associated with colitis via inducing antioxidants and attenuating oxidative stress markers.
      PubDate: 2022-10-01
       
  • A comprehensive insight into the anti-inflammatory properties of dapsone

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      Abstract: The 4,4′-diaminodiphenyl sulfone (DDS), also known as dapsone, is traditionally used as a potent anti-bacterial agent in clinical management of leprosy. For decades, dapsone has been among the first-line medications used in multidrug treatment of leprosy recommended by the World Health Organization (WHO). Shortly after dapsone’s discovery as an antibiotic in 1937, the dual function of dapsone (anti-microbial and anti-inflammatory) was elucidated. Dapsone exerts its anti-bacterial effects by inhibiting dihydrofolic acid synthesis, leading to inhibition of bacterial growth, while its anti-inflammatory properties are triggered by inhibiting reactive oxygen species (ROS) production, reducing the effect of eosinophil peroxidase on mast cells and downregulating neutrophil-mediated inflammatory responses. Among the leading mechanisms associated with its anti-microbial/anti-protozoal effects, dapsone clearly has multiple antioxidant, anti-inflammatory, and anti-apoptotic functions. In this regard, it has been described in treating a wide variety of inflammatory and infectious skin conditions. Previous reports have explored different molecular targets for dapsone and provided insight into the anti-inflammatory mechanism of dapsone. This article reviews several basic, experimental, and clinical approaches on anti-inflammatory effect of dapsone. Graphical abstract
      PubDate: 2022-09-20
       
  • A population pharmacokinetic model of remdesivir and its major metabolites
           based on published mean values from healthy subjects

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      Abstract: Abstract Remdesivir is a direct-acting anti-viral agent. It was originally evaluated against filoviruses. However, during the COVID-19 pandemic, it was investigated due to its anti-viral activities against (SARS-CoV-2) virus. Therefore remdesivir received conditional approval for treatment of patients with severe coronavirus disease. Yet, its pharmacokinetic properties are inadequately understood. This report describes the population pharmacokinetics of remdesivir and its two plasma-detectable metabolites (GS-704277 and GS-441524) in healthy volunteers. The data was extracted from published phase I single escalating and multiple i.v remdesivir dose studies conducted by the manufacturer. The model was developed by standard methods using non-linear mixed effect modeling. Also, a series of simulations were carried out to test suggested clinical doses. The model describes the distribution of remdesivir and each of its metabolites by respective two compartments with sequential metabolism between moieties, and elimination from central compartments. As individual data were not available, only inter-cohort variability could be assessed. The estimated point estimates for central (and peripheral) volumes of distribution for remdesivir, GS-704277, and GS-441524 were 4.89 L (46.5 L), 96.4 L (8.64 L), and 26.2 L (66.2 L), respectively. The estimated elimination clearances of remdesivir, GS704277, and GS-441524 reached 18.1 L/h, 36.9 L/h, and 4.74 L/h, respectively. The developed model described the data well. Simulations of clinically approved doses showed that GS-441524 concentrations in plasma exceeded the reported EC50 values during the complete duration of treatment. Nonetheless, further studies are needed to explore the pharmacokinetics of remdesivir and its relationship to clinical efficacy, and the present model may serve as a useful starting point for additional evaluations.
      PubDate: 2022-09-20
       
  • Gut microbiota involved in spermatogenic function of Sancai Lianmei
           granules in obese mice

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      Abstract: Abstract Obesity is a well-established cause of reduced fertility and semen quality in men. Current evidence suggests that Sancai Lianmei granules (SCLM) effectively improve sexual function and semen quality in diabetic patients, while the gut microbiota can influence disease metabolism through various mechanisms. However, the effect of SCLM on the obesity-induced decrease in semen quality and on the gut microbiota is unclear. This study aimed to investigate the effects of SCLM on spermatogenic function and gut microbiota in obese mice. Obese mice were induced by a high-fat diet, and lipid metabolism, spermatogenic function, inflammatory factors, oxidative stress, and autophagy were analyzed to determine the effects of SCLM and SCLM-fecal microbiota transplantation (FMT). In addition, changes in the gut microbiota of mice were analyzed. SCLM and SCLM + FMT could effectively reduce the levels of total cholesterol (TC), high-density lipoprotein (HDL), and low-density lipoprotein (LDL); decrease the expression of oxidative stress products malondialdehyde (MDA) and 8-hydroxyde-oxyguanosine (8-OHdG); and increase sperm density and sperm viability in obese mice while inhibiting the inflammatory responses and excessive cellular autophagy, indicating that SCLM and SCLM + FMT exerted a protective effect on spermatogenic functions. Furthermore, SCLM affected the gut microbiota composition in mice. This study determined that obesity can lead to reduced sperm motility and affect the composition of the gut microbiota, while SCLM can regulate blood lipids in mice directly or indirectly by regulating gut microbiota changes, and may improve sperm motility in obese mice by reducing oxidative stress and autophagy. In addition, FMT enhanced this effect, which may be related to the diversity of gut microbiota.
      PubDate: 2022-09-20
       
  • Diosmin prophylaxis reduces gentamicin-induced kidney damage in rats

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      Abstract: Abstract Gentamicin is an essential aminoglycoside antibiotic, but it is only used to treat severe bacterial infections due to its high nephrotoxicity in patients. We evaluated the preventive effects of diosmin (as a natural ingredient) on gentamicin-related kidney damage in rats. In this research, 28 male Wistar rats were divided into four groups: control, gentamicin (100 mg/kg (i.p.), daily for 1 week), gentamicin plus diosmin (50 mg/kg, p.o., daily for 2 weeks), and diosmin (50 mg/kg/day, p.o. for 2 weeks). After the final gavage, blood samples were collected for the determination of blood urea nitrogen (BUN) and creatinine. Kidneys are used for biochemical, inflammatory, and histological tests. The concentrations of creatinine, BUN, nitric oxide, malondialdehyde, tumor necrosis factor α (TNF-α), and interleukin 1 beta (IL-1β) were significantly increased. But, the level of glutathione and activities of catalase, glutathione peroxidase, and superoxide dismutase decreased during treatment with gentamicin. On the other hand, the concentrations of creatinine, BUN, nitric oxide, malondialdehyde, TNF-α, and IL-1β were significantly reduced, and the glutathione level, activities of catalase, and glutathione peroxidase were significantly increased via co-administration with diosmin. Diosmin had ameliorative impacts against gentamicin-related kidney injury due to its antioxidant and anti-inflammatory activities.
      PubDate: 2022-09-19
       
  • Evaluation of the oxytocin effect in a rat model with experimental
           periodontitis

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      Abstract: Abstract The aim of the present study was to evaluate the inhibitory effects of oxytocin on the development of periodontitis based on its properties against bone loss and resorption. Thirty-two Wistar albino rats were divided into four equal groups: control, periodontitis + saline, periodontitis + 0.5 mg/kg/day oxytocin, and periodontitis + 1 mg/kg/day oxytocin. Periodontitis groups received 4.0 silk ligatures around their cervixes of the right and left mandibular incisors in an “8” shape, kept for 14 days. Animals in oxytocin groups were injected once every day during 14 days with oxytocin. The mandibles were fixed and scanned using microcomputed tomography to quantify bone resorption and volumetric measurements. Blood samples were collected to analyze the concentrations of macrophage colony-stimulating factor (M-CSF), receptor activator of nuclear factor-κΒ ligand (RANKL), osteoprotegerin (OPG), matrix metalloproteinase-8 (MMP-8), tumor necrosis factor-alpha (TNF-α), interleukin (IL)-6, glutathione peroxidase (GPx), superoxide dismutase (SOD), and malondialdehyde (MDA). Histopathological evaluations were conducted to examine the gingiva and alveolar bone. Oxytocin prevented the development of periodontitis by decreasing ligament deteriorations and leukocytes in the gingival connective tissue and promoting reintegration with the alveolar bone. Bone resorption in all regions was less in the periodontitis + 1 mg/kg/day oxytocin group than in the periodontitis + saline group. Although TNF-α, IL-6, and RANKL values were lower in the periodontitis + 1 mg/kg/day oxytocin group, OPG was higher than that in the periodontitis + saline group. M-CSF, MMP-8, and MDA were lower in the oxytocin groups than in the periodontitis + saline group. Oxytocin may be an effective agent for periodontal diseases because it decreased bone resorption, oxidative stress, and inflammation in an experimental periodontitis.
      PubDate: 2022-09-17
       
  • Nanomedicine and drug delivery to the retina: current status and
           implications for gene therapy

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      Abstract: Abstract Blindness affects more than 60 million people worldwide. Retinal disorders, including age-related macular degeneration (AMD), diabetic retinopathy (DR), and glaucoma, are the leading causes of blindness. Finding means to optimize local and sustained delivery of drugs or genes to the eye and retina is one goal to advance the development of new therapeutics. Despite the ease of accessibility of delivering drugs via the ocular surface, the delivery of drugs to the retina is still challenging due to anatomic and physiologic barriers. Designing a suitable delivery platform to overcome these barriers should enhance drug bioavailability and provide a safe, controlled, and sustained release. Current inventions for posterior segment treatments include intravitreal implants and subretinal viral gene delivery that satisfy these criteria. Several other novel drug delivery technologies, including nanoparticles, micelles, dendrimers, microneedles, liposomes, and nanowires, are now being widely studied for posterior segment drug delivery, and extensive research on gene delivery using siRNA, mRNA, or aptamers is also on the rise. This review discusses the current state of retinal drug/gene delivery and highlights future therapeutic opportunities.
      PubDate: 2022-09-15
       
  • Aspirin reverts lipopolysaccharide-induced learning and memory impairment:
           first evidence from an invertebrate model system

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      Abstract: Abstract By employing a reductionistic (but not simplistic) approach using an established invertebrate model system, the pond snail Lymnaea stagnalis, we investigated whether (1) lipopolysaccharide (LPS)-induced inflammation would cause a sickness state and impair cognitive function, and—if so—(2) would aspirin (acetylsalicylic acid—ASA) restore the impaired cognition. To test our hypotheses, we first determined if the injection of 25 mg (6.25 μg/mL) of Escherichia coli-derived LPS serotype O127:B8 altered homeostatic behavior, aerial respiration, and then determined if LPS altered memory formation when this behavior was operantly conditioned. Next, we determined if ASA altered the LPS-induced changes in both aerial respiration and cognitive functions. LPS induced a sickness state that increased aerial respiration and altered the ability of snails to form or recall long-term memory. ASA reverted the LPS-induced sickness state and thus allowed long-term memory both to be formed and recalled. We confirmed our hypotheses and provided the first evidence in an invertebrate model system that an injection of LPS results in a sickness state that obstructs learning and memory, and this impairment can be prevented by a non-steroidal anti-inflammatory.
      PubDate: 2022-09-14
       
  • Central α7 and α4β2 nicotinic acetylcholine receptors offset arterial
           baroreceptor dysfunction in endotoxic rats

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      Abstract: Abstract Cardiac autonomic neuropathy is a prominent feature of endotoxemia. Given the defensive role of the cholinergic pathway in inflammation, we assessed the roles of central homomeric α7 and heteromeric α4β2 nAChRs in arterial baroreceptor dysfunction caused by endotoxemia in rats. Endotoxemia was induced by i.v. administration of lipopolysaccharides (LPS, 10 mg/kg), and baroreflex activity was measured by the vasoactive method, which assesses reflex chronotropic responses to increments (phenylephrine, PE) or decrements (sodium nitroprusside, SNP) in blood pressure. Shifts caused by LPS in PE/SNP baroreflex curves and associated decreases in baroreflex sensitivity (BRS) were dose-dependently reversed by nicotine (25–100 μg/kg, i.v.). The nicotine effect disappeared after intracisternal administration of methyllycaconitine (MLA) or dihydro-β-erythroidine (DHβE), selective blockers of α7 and α4β2 receptors, respectively. The advantageous effect of nicotine on BRSPE was replicated in rats treated with PHA-543613 (α7-nAChR agonist) or 5-iodo-A-85380 (5IA, α4β2-nAChRs agonist) in dose-dependent fashions. Conversely, the depressed BRSSNP of endotoxic rats was improved after combined, but not individual, treatments with PHA and 5IA. Central α7 and α4β2 nAChR activation underlies the nicotine counteraction of arterial baroreflex dysfunction induced by endotoxemia. Moreover, the contribution of these receptors depends on the nature of the reflex chronotropic response (bradycardia vs. tachycardia).
      PubDate: 2022-09-14
       
  • Taurine mitigates the development of pulmonary inflammation, oxidative
           stress, and histopathological alterations in a rat model of bile duct
           ligation

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      Abstract: Abstract Lung injury is a significant complication associated with cholestasis/cirrhosis. This problem significantly increases the risk of cirrhosis-related morbidity and mortality. Hence, finding effective therapeutic options in this field has significant clinical value. Severe inflammation and oxidative stress are involved in the mechanism of cirrhosis-induced lung injury. Taurine (TAU) is an abundant amino acid with substantial anti-inflammatory and antioxidative properties. The current study was designed to evaluate the role of TAU in cholestasis-related lung injury. For this purpose, bile duct ligated (BDL) rats were treated with TAU (0.5 and 1% w: v in drinking water). Significant increases in the broncho-alveolar lavage fluid (BALF) level of inflammatory cells (lymphocytes, neutrophils, basophils, monocytes, and eosinophils), increased IgG, and TNF-α were detected in the BDL animals (14 and 28 days after the BDL surgery). Alveolar congestion, hemorrhage, and fibrosis were the dominant pulmonary histopathological changes in the BDL group. Significant increases in the pulmonary tissue biomarkers of oxidative stress, including reactive oxygen species formation, lipid peroxidation, increased oxidized glutathione levels, and decreased reduced glutathione, were also detected in the BDL rats. Moreover, significant myeloperoxidase activity and nitric oxide levels were seen in the lung of BDL rats. It was found that TAU significantly blunted inflammation, alleviated oxidative stress, and mitigated lung histopathological changes in BDL animals. These data suggest TAU as a potential protective agent against cholestasis/cirrhosis-related lung injury.
      PubDate: 2022-09-13
       
  • Carvedilol ameliorates dexamethasone-induced myocardial injury in rats
           independent of its action on the α1-adrenergic receptor

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      Abstract: Abstract The current study aimed to investigate the cardiotoxic effect of dexamethasone-high-dose in rats, the therapeutic effect of carvedilol and the role of α1-adrenergic receptor (α1AR). The experiment involved 6 groups: control, dexamethasone (10 mg/kg), carvedilol (10 mg/kg), phenylephrine (1 mg/kg), phenylephrine plus carvedilol and propranolol (30 mg/kg). Drugs and vehicles were given for 7 days. Dexamethasone was given with the drugs in the last 4 groups. On the 8th-day and after overnight fasting, serum and cardiac samples were collected. Serum levels of cardiac troponin I and creatine kinase–myoglobin as well as cardiac levels of diacylglycerol, malondialdehyde, kinase activity of Akt, transforming growth factor-β, Smad3 and alpha smooth muscle actin were measured. Cardiac samples were also used for histopathological examination using hematoxylin–eosin and Sirius red stains, in addition to immunohistochemical examination using β-arrestin2 antibody. Dexamethasone induced cardiac injury via increasing oxidative stress, apoptosis and profibrotic signals. Carvedilol significantly reduced the dexamethasone-induced cardiotoxicity. Using phenylephrine, a competitive α1-agonist, with carvedilol potentiated the cardioprotective actions of carvedilol. Propranolol, a β-blocker without activity on α1ARs, showed higher cardiac protection than carvedilol. Dexamethasone-high-dose upregulates cardiac oxidative stress, apoptotic and profibrotic signals and induces cardiac injury. Blocking the α1-adrenergic receptor by carvedilol attenuates its cardioprotective effects against dexamethasone-induced cardiotoxicity.
      PubDate: 2022-09-10
       
 
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