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  Subjects -> PHARMACY AND PHARMACOLOGY (Total: 575 journals)
Showing 1 - 200 of 253 Journals sorted alphabetically
AAPS Journal     Hybrid Journal   (Followers: 25)
AAPS Open     Open Access   (Followers: 5)
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: 94)
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: 17)
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: 54)
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: 11)
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: 2)
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: 10)
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: 10)
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: 4)
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: 9)
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: 18)
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: 11)
Critical Reviews in Clinical Laboratory Sciences     Hybrid Journal   (Followers: 16)
Critical Reviews in Therapeutic Drug Carrier Systems     Full-text available via subscription   (Followers: 5)
Critical Reviews in Toxicology     Hybrid Journal   (Followers: 25)
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: 2)
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: 5)
Dose-Response     Open Access  
Drug and Chemical Toxicology     Hybrid Journal   (Followers: 13)
Drug and Therapeutics Bulletin     Hybrid Journal   (Followers: 8)
Drug Delivery     Open Access   (Followers: 8)
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: 29)
Drug Development Research     Hybrid Journal   (Followers: 11)
Drug Discovery Today: Technologies     Full-text available via subscription   (Followers: 12)
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: 79)
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: 135)
Drugs & Aging     Full-text available via subscription   (Followers: 9)
Drugs & Therapy Perspectives     Full-text available via subscription   (Followers: 9)
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: 14)
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: 34)
European Journal of Pharmacology     Hybrid Journal   (Followers: 8)
European Neuropsychopharmacology     Hybrid Journal   (Followers: 9)
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: 17)
Expert Opinion on Drug Discovery     Hybrid Journal   (Followers: 18)

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Toxicological Sciences
Journal Prestige (SJR): 1.538
Citation Impact (citeScore): 4
Number of Followers: 11  
 
  Hybrid Journal Hybrid journal (It can contain Open Access articles)
ISSN (Print) 1096-6080 - ISSN (Online) 1096-0929
Published by Oxford University Press Homepage  [419 journals]
  • Microphysiological Systems Evaluation: Experience of TEX-VAL Tissue Chip
           Testing Consortium

    • Free pre-print version: Loading...

      Pages: 143 - 152
      Abstract: AbstractMuch has been written and said about the promise and excitement of microphysiological systems, miniature devices that aim to recreate aspects of human physiology on a chip. The rapid explosion of the offerings and persistent publicity placed high expectations on both product manufacturers and regulatory agencies to adopt the data. Inevitably, discussions of where this technology fits in chemical testing paradigms are ongoing. Some end-users became early adopters, whereas others have taken a more cautious approach because of the high cost and uncertainties of their utility. Here, we detail the experience of a public-private collaboration established for testing of diverse microphysiological systems. Collectively, we present a number of considerations on practical aspects of using microphysiological systems in the context of their applications in decision-making. Specifically, future end-users need to be prepared for extensive on-site optimization and have access to a wide range of imaging and other equipment. We reason that cells, related reagents, and the technical skills of the research staff, not the devices themselves, are the most critical determinants of success. Extrapolation from concentration-response effects in microphysiological systems to human blood or oral exposures, difficulties with replicating the whole organ, and long-term functionality remain as critical challenges. Overall, we conclude that it is unlikely that a rodent- or human-equivalent model is achievable through a finite number of microphysiological systems in the near future; therefore, building consensus and promoting the gradual incorporation of these models into tiered approaches for safety assessment and decision-making is the sensible path to wide adoption.
      PubDate: Sat, 11 Jun 2022 00:00:00 GMT
      DOI: 10.1093/toxsci/kfac061
      Issue No: Vol. 188, No. 2 (2022)
       
  • Phthalate Exposures and Placental Health in Animal Models and Humans: A
           Systematic Review

    • Free pre-print version: Loading...

      Pages: 153 - 179
      Abstract: AbstractPhthalates are ubiquitous compounds known to leach from the plastic products that contain them. Due to their endocrine-disrupting properties, a wide range of studies have elucidated their effects on reproduction, metabolism, neurodevelopment, and growth. Additionally, their impacts during pregnancy and on the developing fetus have been extensively studied. Most recently, there has been interest in the impacts of phthalates on the placenta, a transient major endocrine organ critical to maintenance of the uterine environment and fetal development. Phthalate-induced changes in placental structure and function may have significant impacts on the course of pregnancy and ultimately, child health. Prior reviews have described the literature on phthalates and placental health; however to date, there has been no comprehensive, systematic review on this topic. Here, we review 35 papers (24 human and 11 animal studies) and summarize phthalate exposures in relation to an extensive set of placental measures. Phthalate-related alterations were reported for placental morphology, hormone production, vascularization, histopathology, and gene/protein expression. The most consistent changes were observed in vascular and morphologic endpoints, including cell composition. These changes have implications for pregnancy complications such as preterm birth and intrauterine growth restriction as well as potential ramifications for children’s health. This comprehensive review of the literature, including common sources of bias, will inform the future work in this rapidly expanding field.
      PubDate: Fri, 10 Jun 2022 00:00:00 GMT
      DOI: 10.1093/toxsci/kfac060
      Issue No: Vol. 188, No. 2 (2022)
       
  • An Interactive Generic Physiologically Based Pharmacokinetic (igPBPK)
           Modeling Platform to Predict Drug Withdrawal Intervals in Cattle and
           Swine: A Case Study on Flunixin, Florfenicol, and Penicillin G

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      Pages: 180 - 197
      Abstract: AbstractViolative chemical residues in edible tissues from food-producing animals are of global public health concern. Great efforts have been made to develop physiologically based pharmacokinetic (PBPK) models for estimating withdrawal intervals (WDIs) for extralabel prescribed drugs in food animals. Existing models are insufficient to address the food safety concern as these models are either limited to 1 specific drug or difficult to be used by non-modelers. This study aimed to develop a user-friendly generic PBPK platform that can predict tissue residues and estimate WDIs for multiple drugs including flunixin, florfenicol, and penicillin G in cattle and swine. Mechanism-based in silico methods were used to predict tissue/plasma partition coefficients and the models were calibrated and evaluated with pharmacokinetic data from Food Animal Residue Avoidance Databank (FARAD). Results showed that model predictions were, in general, within a 2-fold factor of experimental data for all 3 drugs in both species. Following extralabel administration and respective U.S. FDA-approved tolerances, predicted WDIs for both cattle and swine were close to or slightly longer than FDA-approved label withdrawal times (eg, predicted 8, 28, and 7 days vs labeled 4, 28, and 4 days for flunixin, florfenicol, and penicillin G in cattle, respectively). The final model was converted to a web-based interactive generic PBPK platform. This PBPK platform serves as a user-friendly quantitative tool for real-time predictions of WDIs for flunixin, florfenicol, and penicillin G following FDA-approved label or extralabel use in both cattle and swine, and provides a basis for extrapolating to other drugs and species.
      PubDate: Wed, 01 Jun 2022 00:00:00 GMT
      DOI: 10.1093/toxsci/kfac056
      Issue No: Vol. 188, No. 2 (2022)
       
  • Exploring the Influence of Experimental Design on Toxicity Outcomes in
           Zebrafish Embryo Tests

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      Pages: 198 - 207
      Abstract: AbstractCompound toxicity data obtained from independent zebrafish laboratories can vary vastly, complicating the use of zebrafish screening for regulatory decisions. Differences in the assay protocol parameters are the primary source of variability. We investigated this issue by utilizing data from the NTP DNT-DIVER database (https://doi.org/10.22427/NTP-DATA-002-00062-0001-0000-1, last accessed June 2, 2022), which consists of data from zebrafish developmental toxicity (devtox) and locomotor response (designated as “neurotox”) screens from 3 independent laboratories, using the same set of 87 compounds. The data were analyzed using the benchmark concentration (BMC) modeling approach, which estimates the concentration of interest based on a predetermined response threshold. We compared the BMC results from 3 laboratories (A, B, C) in 3 toxicity outcome categories: mortality, cumulative devtox, and neurotox, in terms of activity calls and potency values. We found that for devtox screening, laboratories with similar/same protocol parameters (B vs C) had an active call concordance as high as 86% with negligible potency difference. For neurotox screening, active call concordances between paired laboratories are lower than devtox screening (highest 68%). When protocols with different protocol parameters were compared, the concordance dropped, and the potency shift was on average about 3.8-fold for the cumulative devtox outcome and 5.8-fold for the neurotox outcome. The potential contributing protocol parameters for potency shift are listed or ranked. This study provides a quantitative assessment of the source of variability in zebrafish screening protocols and sets the groundwork for the ongoing Systematic Evaluation of the Application of Zebrafish in Toxicology effort at the National Toxicology Program.
      PubDate: Fri, 27 May 2022 00:00:00 GMT
      DOI: 10.1093/toxsci/kfac053
      Issue No: Vol. 188, No. 2 (2022)
       
  • Early Drug-Induced Liver Injury Risk Screening: “Free,” as
           Good as It Gets

    • Free pre-print version: Loading...

      Pages: 208 - 218
      Abstract: AbstractFor all the promise of and need for clinical drug-induced liver injury (DILI) risk screening systems, demonstrating the predictive value of these systems versus readily available physicochemical properties and inherent dosing information has not been thoroughly evaluated. Therefore, we utilized a systematic approach to evaluate the predictive value of in vitro safety assays including bile salt export pump transporter inhibition and cytotoxicity in HepG2 and transformed human liver epithelial along with physicochemical properties. We also evaluated the predictive value of in vitro ADME assays including hepatic partition coefficient (Kp) and its unbound counterpart because they provide insight on hepatic accumulation potential. The datasets comprised of 569 marketed drugs with FDA DILIrank annotation (most vs less/none), dose and physicochemical information, 384 drugs with Kp and plasma protein binding data, and 279 drugs with safety assay data. For each dataset and combination of input parameters, we developed random forest machine learning models and measured model performance using the receiver operator characteristic area under the curve (ROC AUC). The median ROC AUC across the various data and parameters sets ranged from 0.67 to 0.77 with little evidence of additive predictivity when including safety or ADME assay data. Subsequent machine learning models consistently demonstrated daily dose, fraction sp3 or ionization, and cLogP/D inputs produced the best, simplest model for predicting clinical DILI risk with an ROC AUC of 0.75. This systematic framework should be used for future assay predictive value assessments and highlights the need for continued improvements to clinical DILI risk annotation.
      PubDate: Fri, 27 May 2022 00:00:00 GMT
      DOI: 10.1093/toxsci/kfac054
      Issue No: Vol. 188, No. 2 (2022)
       
  • Nanomaterial Inhalation During Pregnancy Alters Systemic Vascular Function
           in a Cyclooxygenase-Dependent Manner

    • Free pre-print version: Loading...

      Pages: 219 - 233
      Abstract: AbstractPregnancy requires rapid adaptations in the uterine microcirculation to support fetal development. Nanomaterial inhalation is associated with cardiovascular dysfunction, which may impair gestation. We have shown that maternal nano-titanium dioxide (nano-TiO2) inhalation impairs microvascular endothelial function in response to arachidonic acid and thromboxane (TXA2) mimetics. However, the mechanisms underpinning this process are unknown. Therefore, we hypothesize that maternal nano-TiO2 inhalation during gestation results in uterine microvascular prostacyclin (PGI2) and TXA2 dysfunction. Pregnant Sprague-Dawley rats were exposed from gestational day 10–19 to nano-TiO2 aerosols (12.17  ± 1.67 mg/m3) or filtered air (sham-control). Dams were euthanized on gestational day 20, and serum, uterine radial arterioles, implantation sites, and lungs were collected. Serum was assessed for PGI2 and TXA2 metabolites. TXB2, the stable TXA2 metabolite, was significantly decreased in nano-TiO2 exposed dams (597.3 ± 84.4 vs 667.6 ± 45.6 pg/ml), whereas no difference was observed for 6-keto-PGF1α, the stable PGI2 metabolite. Radial arteriole pressure myography revealed that nano-TiO2 exposure caused increased vasoconstriction to the TXA2 mimetic, U46619, compared with sham-controls (−41.3% ± 4.3% vs −16.8% ± 3.4%). Nano-TiO2 exposure diminished endothelium-dependent vasodilation to carbaprostacyclin, a PGI2 receptor agonist, compared with sham-controls (30.0% ± 9.0% vs 53.7% ± 6.0%). Maternal nano-TiO2 inhalation during gestation decreased nano-TiO2 female pup weight when compared with sham-control males (3.633 ± 0.064 vs 3.995 ± 0.124 g). Augmented TXA2 vasoconstriction and decreased PGI2 vasodilation may lead to decreased placental blood flow and compromise maternofetal exchange of waste and nutrients, which could ultimately impact fetal health outcomes.
      PubDate: Wed, 01 Jun 2022 00:00:00 GMT
      DOI: 10.1093/toxsci/kfac055
      Issue No: Vol. 188, No. 2 (2022)
       
  • In Utero Exposure to a Mixture of the Perfluoroalkyl-Isopropyl Pesticide
           Pyrifluquinazon With Dibutyl Phthalate Cumulatively Disrupts Male Rat
           Reproductive Development via Different Mechanisms of Action

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      Pages: 234 - 247
      Abstract: AbstractAdministration of individual chemicals and mixtures during sexual differentiation that disrupt the androgen signaling pathway can induce reproductive abnormalities in male rats. In this study, we coadministered the heptafluoroisopropyl pesticide pyrifluquinazon (PFQ), and dibutyl phthalate (DBP) to pregnant rats during sexual differentiation of the reproductive tract. Both chemicals have been shown to disrupt reproductive tract differentiation in a dose-related manner reducing male anogenital distance, permanently reducing androgen-dependent tissue weights and sperm counts, and inducing reproductive malformations in male offspring, albeit by different mechanisms of action that converge downstream in the androgen signaling pathway on a common key event. Rats were orally dosed from gestation days 14–18 with dilutions of PFQ and DBP at 0%, 12.5%, 25%, 50%, 75%, and 100% of the top dose (100 mg/kg PFQ and 750 mg/kg DBP). The mixture ratio was selected such that each chemical would contribute equally to multiple effects on the male offspring reproductive tract and the dose range was designed to determine if the mixture produced additive effects predicted by dose addition (DA) or response addition (RA) models, or whether significant interactions occurred. Observed data were compared with DA and RA model predictions. As hypothesized, the mixture reduced F1 male anogenital distance, reproductive organ weights and sperm counts and induced hypospadias with DA consistently providing a better prediction of the observed effects than RA. These results support our hypothesis that chemicals that disrupt the androgen signaling pathway induce dose-additive male reproductive abnormalities regardless of the specific mechanism of action.
      PubDate: Wed, 01 Jun 2022 00:00:00 GMT
      DOI: 10.1093/toxsci/kfac059
      Issue No: Vol. 188, No. 2 (2022)
       
  • Recovered Hepatocytes Promote Macrophage Apoptosis Through CXCR4 After
           Acetaminophen-Induced Liver Injury in Mice

    • Free pre-print version: Loading...

      Pages: 248 - 260
      Abstract: AbstractAcetaminophen (APAP) overdose is the main cause of acute liver failure in Western countries. The mechanism of APAP hepatotoxicity is associated with centrilobular necrosis which initiates infiltration of neutrophils, monocytes, and other leukocytes to the area of necrosis. Although it has been recognized that this infiltration of immune cells plays a critical role in promoting liver repair, mechanism of immune cell clearance that is important for resolution of inflammation and the return to normal homeostasis are not well characterized. CXCR4 is a chemokine receptor expressed on hepatocytes as well as neutrophils, monocytes, and hematopoietic stem cells. CXCR4 function is dependent on its selective expression on different cell types and thus can vary depending on the pathophysiology. This study aimed to investigate the crosstalk between hepatocytes and macrophages through CXCR4 to promote macrophage apoptosis after APAP overdose. C57BL/6J mice were subjected to APAP overdose (300 mg/kg). Flow cytometry and immunohistochemistry were used to determine the mode of cell death of macrophages and expression pattern of CXCR4 during the resolution phase of APAP hepatotoxicity. The impact of CXCR4 in regulation of macrophage apoptosis and liver recovery was assessed after administration of a monoclonal antibody against CXCR4. RNA sequencing analysis was performed on flow cytometry sorted CXCR4+ macrophages at 72 h to confirm the apoptotic cell death of macrophages. Our data indicate that the inflammatory response is resolved by recovering hepatocytes through induction of CXCR4 on macrophages, which triggers their cell death by apoptosis at the end of the recovery phase.
      PubDate: Wed, 01 Jun 2022 00:00:00 GMT
      DOI: 10.1093/toxsci/kfac057
      Issue No: Vol. 188, No. 2 (2022)
       
  • Impact of Surface Chemistry of Ultrasmall Superparamagnetic Iron Oxide
           Nanoparticles on Protein Corona Formation and Endothelial Cell Uptake,
           Toxicity, and Barrier Function

    • Free pre-print version: Loading...

      Pages: 261 - 275
      Abstract: AbstractUltrasmall superparamagnetic iron oxide nanoparticles (USPIONs) have been investigated for biomedical applications, including novel contrast agents, magnetic tracers for tumor imaging, targeted drug delivery vehicles, and magneto-mechanical actuators for hyperthermia and thrombolysis. Despite significant progress, recent clinical reports have raised concerns regarding USPION safety related to endothelial cell dysfunction; however, there is limited information on factors contributing to these clinical responses. The influence of USPION surface chemistry on nanoparticle interactions with proteins may impact endothelial cell function leading to adverse responses. Therefore, the goal of this study was to assess the effects of carboxyl-functionalized USPION (CU) or amine-functionalized USPION (AU) (approximately 30 nm diameter) on biological responses in human coronary artery endothelial cells. Increased protein adsorption was observed for AU compared with CU after exposure to serum proteins. Exposure to CU, but not AU, resulted in a concentration-dependent decrease in cell viability and perinuclear accumulation inside cytoplasmic vesicles. Internalization of CU was correlated with endothelial cell functional changes under non-cytotoxic conditions, as evidenced by a marked decreased expression of endothelial-specific adhesion proteins (eg, vascular endothelial-cadherin and platelet endothelial cell adhesion molecule-1) and increased endothelial permeability. Evaluation of downstream signaling indicated endothelial permeability is associated with actin cytoskeleton remodeling, possibly elicited by intracellular events involving reactive oxygen species, calcium ions, and the nanoparticle cellular uptake pathway. This study demonstrated that USPION surface chemistry significantly impacts protein adsorption and endothelial cell uptake, viability, and barrier function. This information will advance the current toxicological profile of USPION and improve development, safety assessment, and clinical outcomes of USPION-enabled medical products.
      PubDate: Thu, 16 Jun 2022 00:00:00 GMT
      DOI: 10.1093/toxsci/kfac058
      Issue No: Vol. 188, No. 2 (2022)
       
  • Correction to: Inhalation toxicity and carcinogenicity studies of cobalt
           sulfate

    • Free pre-print version: Loading...

      Pages: 276 - 276
      Abstract: This is a correction to: JR Bucher, JR Hailey, JR Roycroft, JK Haseman, RC Sills, SL Grumbein, P W Mellick, BJ Chou, Inhalation toxicity and carcinogenicity studies of cobalt sulfate, Toxicological Sciences, Volume 49, Issue 1, May 1999, Pages 56–67, https://doi.org/10.1093/toxsci/49.1.56
      PubDate: Mon, 20 Jun 2022 00:00:00 GMT
      DOI: 10.1093/toxsci/kfac063
      Issue No: Vol. 188, No. 2 (2022)
       
 
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