BMC Pharmacology & Toxicology最新文献

{"title":"Effect of single intravenous injection of esketamine on postpartum depression after labor analgesia and potential mechanisms: a randomized, double-blinded controlled trial.","authors":"Bin Ling, Yun Zhu, Zelin Yan, Hao Chen, Hua Xu, Qi Wang, Wanyou Yu, Wei Wang","doi":"10.1186/s40360-023-00705-7","DOIUrl":"10.1186/s40360-023-00705-7","url":null,"abstract":"<p><strong>Background: </strong>The study was designed to investigate effects of single intravenous injection of esketamine on the incidence of postpartum depression (PPD) after labor analgesia and explore the potential mechanisms.</p><p><strong>Methods: </strong>A total of 120 women who underwent labor analgesia by epidural analgesia pump were enrolled and divided into two groups randomly. Esketamine at a dose of 0.2 mg/kg was intravenously injected after fetal disengagement in the test group and placebo was administered in the control group. The occurrence of PPD and side effects after delivery were recorded. Some indicators related to stress and inflammation were measured before labor analgesia and at 24 h, 1 week, and 6 weeks after delivery in this study. Data were analyzed by independent t-test, repeated measures analysis of variance and Chi-square test in SPSS software (version 25.0). It was considered statistically significant since a p value less than 0.05.</p><p><strong>Results: </strong>The incidence of PPD was significantly decreased both for one week and six weeks after delivery by using of esketamine (3.4% vs. 15.3%, p = 0.004 and 5.2% vs. 18.6%, p = 0.006, respectively). There were also significant differences between the stress and inflammation-related indicators in different time points in this study, while the side effects for 48 h after delivery were similar between the two groups.</p><p><strong>Conclusions: </strong>Single intravenous injection of esketamine after delivery in participants underwent labor analgesia can decrease the occurrence of postpartum depression for one week and six weeks after delivery, while the side effects were not increased. The antidepressant effects of esketamine may be related to the reduction of stress response and inflammation.</p><p><strong>Trial registration: </strong>The trial was registered at the Chinese Clinical Trial Registry on 5/30/2022 (CTRI registration number-ChiCTR2200060387). URL of registry: https://www.chictr.org.cn/bin/home .</p>","PeriodicalId":9023,"journal":{"name":"BMC Pharmacology & Toxicology","volume":"24 1","pages":"66"},"PeriodicalIF":2.9,"publicationDate":"2023-11-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10668401/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138298265","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The effect of acarbose on lipid profiles in adults: a systematic review and meta-analysis of randomized clinical trials.","authors":"Mohsen Yousefi, Sahand Tehrani Fateh, Mahlagha Nikbaf-Shandiz, Fatemeh Gholami, Samira Rastgoo, Reza Bagher, Alireza Khadem, Farideh Shiraseb, Omid Asbaghi","doi":"10.1186/s40360-023-00706-6","DOIUrl":"10.1186/s40360-023-00706-6","url":null,"abstract":"<p><strong>Purpose: </strong>Dyslipidemia, characterized by elevated levels of triglycerides (TG), low-density lipoprotein (LDL), total cholesterol (TC), and reduced levels of high-density lipoprotein (HDL), is a major risk factor for cardiovascular diseases (CVD). Several studies have shown the potential of acarbose in improving serum lipid markers. However, there have been conflicting results on the topic in adults. Therefore, a comprehensive systematic review and meta-analysis was conducted to assess the impact of acarbose on lipid profiles.</p><p><strong>Methods: </strong>The random-effects approach was used to combine the data, and the results were provided as weighted mean difference (WMD) with 95% confidence intervals (CI).</p><p><strong>Results: </strong>Our meta-analysis included a total of 74 studies with a combined sample size of 7046 participants. The results of the analysis showed that acarbose resulted in a reduction in levels of TG (WMD = - 13.43 mg/dl, 95% CI: - 19.20, - 7.67; P < 0.001) and TC (WMD = - 1.93 mg/dl, 95% CI: - 3.71, - 0.15; P = 0.033), but did not affect other lipid markers. When conducting a nonlinear dose-response analysis, we found that acarbose was associated with an increase in levels of HDL (coefficients = 0.50, P = 0.012), with the highest increase observed at a dosage of 400 mg/d. Furthermore, our findings suggested a non-linear relationship between the duration of the intervention and TC (coefficients = - 18.00, P = 0.032), with a decline observed after 50 weeks of treatment.</p><p><strong>Conclusion: </strong>The findings of this study suggest that acarbose can reduce serum levels of TG and TC. However, no significant effects were observed on LDL or HDL levels.</p>","PeriodicalId":9023,"journal":{"name":"BMC Pharmacology & Toxicology","volume":"24 1","pages":"65"},"PeriodicalIF":2.9,"publicationDate":"2023-11-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10664642/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138290262","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Study on the association between adverse drug reactions to opioids and gene polymorphisms: a case-case-control study.","authors":"Jing Yang, Ying-Zi Sun, Qun-Fang Li, Zheng Fu, Yu-Yao Guan, Chao Song, Lei Zheng","doi":"10.1186/s40360-023-00708-4","DOIUrl":"10.1186/s40360-023-00708-4","url":null,"abstract":"<p><strong>Objective: </strong>Adverse drug reactions (ADRs) caused by opioid drugs show individual differences. Our objective was to explore the association between gene polymorphism and ADRs induced by opioid drugs.</p><p><strong>Methods: </strong>Evidence-based medical data analysis was conducted for genes related to ADRs induced by opioid drugs to select target genes. Sixty patients with cancer pain who had ADRs after taking opioid drugs (morphine, codeine, oxycodone) and 60 patients without ADRs after taking opioid drugs were used as the experimental group and control group, respectively. Then, we used polymerase chain reaction (PCR) or in situ hybridization to detect target genes. By combining with clinical data such as age, sex, dosage and duration of medication, the effect of gene polymorphism on the ADR of patients after taking opioid drugs was statistically analysed.</p><p><strong>Results: </strong>Based on a database search and evidence-based medical data, we identified CYP2D6*10, CYP3A5*3, ABCB1, and OPRM1 as target genes for detection. The results of statistical analysis showed no significant difference in genotype distribution between the experimental group and the control group (p > 0.05). However, if 32 patients with ADRs after taking oxycodone and 32 controls were selected for comparison, the SPSS22.0 and SNPStats genetic models showed that the ABCB1 (062rs1045642) CT and TT genotypes correlated with the occurrence of ADRs (p < 0.05): the total number of CT + TT genotypes in the experimental group was 29 (90.62%), with 11 (34.37%) CT + TT genotypes types in the control group.</p><p><strong>Conclusion: </strong>Polymorphism of ABCB1 (062rs1045642) is related to ADRs caused by oxycodone, and the incidence of ADRs is higher with the allele T. Polymorphism of ABCB1 is expected to become a clinical predictor of ADRs to oxycodone, and attention should be given to the occurrence of serious ADRs in patients with ABCB1 (062rs1045642) CT and TT genotypes.</p>","PeriodicalId":9023,"journal":{"name":"BMC Pharmacology & Toxicology","volume":"24 1","pages":"64"},"PeriodicalIF":2.9,"publicationDate":"2023-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10662635/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138290261","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Bisdemethoxycurcumin alleviates LPS-induced acute lung injury via activating AMPKα pathway.","authors":"Huifang Li, Qi Zou, Xueming Wang","doi":"10.1186/s40360-023-00698-3","DOIUrl":"10.1186/s40360-023-00698-3","url":null,"abstract":"<p><strong>Objective: </strong>Inflammation and oxidative stress contribute to the pathogenesis of acute lung injury (ALI), and subsequently result in rapid deterioration in health. Considering the indispensable role of bisdemethoxycurcumin (BDMC) in inflammation and oxidative stress, the present study aims to examine the effect of BDMC on sepsis-related ALI.</p><p><strong>Methods: </strong>C57BL/6 mice were administered with BDMC (100 mg/kg) or an equal volume of vehicle, and then injected with lipopolysaccharides (LPS) to induce ALI. We assessed the parameters of lung injury, inflammatory response and oxidative stress in lung tissues. Consistently, the macrophages with or without BDMC treatment were exposed to LPS to verify the effect of BDMC in vitro.</p><p><strong>Results: </strong>BDMC suppressed LPS-induced lung injury, inflammation and oxidative stress in vivo and in vitro. Mechanistically, BDMC increased the phosphorylation of AMPKα in response to LPS stimulation, and AMPK inhibition with Compound C almost completely blunted the protective effect of BDMC in LPS-treated mice and macrophages. Moreover, we demonstrated that BDMC activated AMPKα via the cAMP/Epac pathway.</p><p><strong>Conclusion: </strong>Our study identifies the protective effect of BDMC against LPS-induced ALI, and the underlying mechanism may be related to the activation of cAMP/Epac/AMPKα signaling pathway.</p>","PeriodicalId":9023,"journal":{"name":"BMC Pharmacology & Toxicology","volume":"24 1","pages":"63"},"PeriodicalIF":2.9,"publicationDate":"2023-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10662695/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138175546","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A disproportionality analysis of adverse events associated to pertuzumab in the FDA Adverse Event Reporting System (FAERS).","authors":"Shu-Peng Zou, Hai-Yun Yang, Meng-Ling Ouyang, Qian Cheng, Xuan Shi, Ming-Hui Sun","doi":"10.1186/s40360-023-00702-w","DOIUrl":"10.1186/s40360-023-00702-w","url":null,"abstract":"<p><strong>Background: </strong>Pertuzumab is widely used for the treatment of HER2 + breast cancer. But its safety in the real world should be continuously monitored. So, we evaluated the safety of pertuzumab by pharmacovigilance analyze based on related adverse events (AEs) from the FDA Adverse Event Reporting System (FAERS) and find whether potential or uncertain adverse events were present.</p><p><strong>Methods: </strong>In disproportionality analysis, four algorithms were employed to detect the signals of pertuzumab from the FAERS between 2012 and 2022. In addition, we also used MYSQL 8.0, Navicat Premium 15, and Microsoft EXCEL 2019 to analyze the potential and high-ROR (reporting odds ratio) signals of pertuzumab. We also collected the onset times of pertuzumab-associated AEs.</p><p><strong>Results: </strong>From January 2012 to December 2022, there are 39,190,598 AEs reported from the FAERS database, of which 14,707 AEs listed pertuzumab as the 'primary suspected (PS)' drug. A total of 115 (46 potential) significant disproportionality preferred terms (PTs) conforming to the four algorithms were retained. Finally, we detected that the pertuzumab-induced AEs occurred in 12 organ systems. For pertuzumab, unexpected and significant PTs of AEs were found, including but not limited to below PTs: haematotoxicity, cardiotoxicity, cardiomyopathy, mitral valve incompetence, tachycardia, intestinal perforation, hemorrhoids, erysipelas, dehydration, pneumonitis, skin toxicity, onychomadesis, cyanosis, and circulatory collapse. We found there were 9 strong signals (5 potential safety signals) and 68 medium intensity signals (21 potential safety signals) according to IC₀₂₅ (information component). The potential strong signals (IC₀₂₅ > 3.0) were myelosuppression, cardiotoxicity, cardiac dysfunction, ejection fraction decreased, interstitial lung disease, and onychomadesis. Excluding unreported or unreasonable onset time reports, a total of 2016 AEs reported onset time and the median onset time was 117 days (4, 96), as median (Q1, Q3). Notably, most of the all AEs (n = 1133, 56%) and cardiac-related events (n = 405, 53%) all occurred within one month after pertuzumab therapy.</p><p><strong>Conclusion: </strong>Analysis of FAERS data identified pertuzumab-associated AEs, and our findings supported continuous clinical monitoring, pharmacovigilance, and further studies of pertuzumab. A significant association was detected between pertuzumab and some potential adverse events which should be regarded with some care. We have to pay attention to the first month after pertuzumab therapy and prepare emergency measures, especially for the elderly and patients with cardiovascular diseases.</p>","PeriodicalId":9023,"journal":{"name":"BMC Pharmacology & Toxicology","volume":"24 1","pages":"62"},"PeriodicalIF":2.9,"publicationDate":"2023-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10642055/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"92152645","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"In vitro evaluation of cell viability and expression profile of growth factors in mouse Sertoli cells exposed to Delta-9-tetrahydrocannabinol: a mechanistic insight into the cannabinoid-induced testicular toxicity.","authors":"Shadi Mohammadpour-Asl, Shiva Roshan-Milani, Amin Abdollahzade Fard, Ali Golchin","doi":"10.1186/s40360-023-00704-8","DOIUrl":"10.1186/s40360-023-00704-8","url":null,"abstract":"<p><p>The potentially adverse effects of cannabis (marijuana), a common leisure compound, on male reproductive performance are a reason for concern. δ-9-tetrahydrocannabinol (THC), the primary active component of marijuana alters testicular cells' proliferation and function which affects male fertility and causes testicular cells dysfunction and apoptosis. The main objective of this study was to investigate the possible mechanism underlying the toxic effects of THC with a mechanistic insight into Sertoli cell-based reproductive dysfunction. The Mus musculus Sertoli cell line (TM4) was cultured and exposed to different concentrations of THC and, MTT (3-(4, 5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay was then performed for evaluating cell viability. The expression of caspase-3 gene and genes related to growth factors were analyzed by real-time RT-PCR. Western blotting was performed for evaluating protein expression level. THC concentration-dependently decreased the TM4 viability with a significant effect starting at concentration of 1 μM and reaching about 75% of the control level at the concentration of 50 μM (IC₂₅). Moreover, caspase-3 mRNA expression levels significantly increased while growth factors mRNA levels decreased in THC-exposed cells compared to unexposed cells. There was also a significant reduction in related protein levels in THC group. Administration of the THC promotes cytotoxic and apoptotic effects on TM4 cells partly through down-regulation of growth factors expression. Increased apoptosis, over expression of caspase-3, and down-regulation of growth factors expression in Sertoli cells exposed to THC may be a reflection of THC-induced testicular toxicity, which may be partly involved in infertility associated with marijuana smoking or medical cannabis use.</p>","PeriodicalId":9023,"journal":{"name":"BMC Pharmacology & Toxicology","volume":"24 1","pages":"61"},"PeriodicalIF":2.9,"publicationDate":"2023-11-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10636832/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"72013379","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sericin alleviates motor dysfunction by modulating inflammation and TrkB/BDNF signaling pathway in the rotenone-induced Parkinson's disease model.","authors":"Zahra Salari, Ghorbangol Ashabi, Ali Fartoosi, Ahmad Fartoosi, Marjan Shariatpanahi, Mehdi Aghsami, Hamed Montazeri, Afshin Kheradmand","doi":"10.1186/s40360-023-00703-9","DOIUrl":"10.1186/s40360-023-00703-9","url":null,"abstract":"<p><strong>Background: </strong>Parkinson's disease (PD) is a progressive neurodegenerative disorder characterized by the degeneration of nigrostriatal dopaminergic neurons and movement impairment. Based on theories, neuroinflammatory processes may be vital in the etiology of PD and other neurodegenerative diseases. Reports show that rotenone has neurotoxic, inflammatory, and motor impairment effects in PD. Sericin is a natural polymer with effective properties, such as neuroprotective and anti-inflammatory. Therefore, this study aimed to examine the effects of sericin administration on motor dysfunction by modulating inflammation and tyrosine kinase B/brain-derived neurotrophic factor (TrkB/BDNF) pathway in the rotenone-induced PD model.</p><p><strong>Methods: </strong>Wistar male rats (3-months-old) were treated with rotenone (2 mg/kg every 48 h for 30 days) to induce a rotenone-induced PD model. Also, sericin was administered orally at dose of 200 mg/kg every 48 h for 30 days. Rotarod and bar tests were performed for motor dysfunction. The protein levels of BDNF, c-fos, TrkB, tumor necrosis factor- α (TNF-α), interleukin-6 (IL-6) and catalase activity were evaluated in the striatum area.</p><p><strong>Results: </strong>Results showed that sericin increased latent time in the rotarod test and decreased the time staying on the pole in the bar test compared to the PD group (P < 0.001 for both tests). Moreover, sericin treatments decreased TNF-α (P < 0.001) and IL-6 (P < 0.001) concentration levels and enhanced the levels of BDNF (P < 0.001), c-fos (P < 0.001), TrkB (P < 0.001) proteins and catalase activity (P < 0.05) in the striatum area compared to the PD group.</p><p><strong>Conclusion: </strong>These results support a protective benefit of sericin therapy in a rotenone-induced PD paradigm by reducing motor impairment, inflammatory response, and disruption of the TrkB/BDNF signaling pathway.</p>","PeriodicalId":9023,"journal":{"name":"BMC Pharmacology & Toxicology","volume":"24 1","pages":"60"},"PeriodicalIF":2.9,"publicationDate":"2023-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10631121/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71477709","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Efficacy of intravenous N acetylcysteine as an adjuvant therapy in the treatment of acute aluminum phosphide Poisoning: a systematic review and meta-analysis.","authors":"Heba Othman Shaker,&nbsp;Omar El Sayed Rageh,&nbsp;Maged Alnajar,&nbsp;Nesreen Fares Alshamaly,&nbsp;Walaa Abdelfattah Abdelmaged,&nbsp;Mohamed Abd-ElGawad","doi":"10.1186/s40360-023-00699-2","DOIUrl":"https://doi.org/10.1186/s40360-023-00699-2","url":null,"abstract":"<p><strong>Background: </strong>Aluminum phosphide toxicity is a serious problem in many countries. Unfortunately, there is no specific antidote. N-acetylcysteine has been used in some studies as adjuvant therapy depending on to its antioxidant properties. We hypothesized that IV N-acetylcysteine is effective in reducing mortality rate compared to supportive treatment alone.</p><p><strong>Methods: </strong>We searched in PubMed, Scopus, Web of Science, and Cochrane Library databases. We only included randomized controlled trials that assessed the efficacy of IV N-acetylcysteine and supportive treatment versus supportive treatment alone in acute aluminum phosphide poisoning. Four investigators independently screened the studies' results and designed the data extraction sheet. The primary and secondary outcomes were mortality and the need for mechanical ventilation rates. Random effects estimators with weights were used to result in the pooled risk ratios.</p><p><strong>Results: </strong>We included four randomized controlled trials with 177 patients. 91 patients were distributed in N-acetylcysteine group and 86 patients in the control group. Mortality rates in N-acetylcysteine group and in the control group were 43.95% 66.27% respectively. There was a statistically significant reduction in mortality rate after leave out test (pooled risk ratio, 0.5; 95% confidence interval, 0.32-0.77). Regarding the need for mechanical ventilation, it was measured only in three RCTs. It was assessed in 67 patients in N-acetylcysteine group and 60 patients in the control group. 24 patients were ventilated in N-acetylcysteine group (35.8%) and 29 patients in the control group (48.3%). But it was statistically nonsignificant (pooled risk ratio, 0.71; 95% confidence interval, 0.48-1.04).</p><p><strong>Conclusion: </strong>Our meta-analysis revealed that IV N-acetylcysteine may be effective in reducing mortality of severe aluminum phosphide poisoning cases.</p><p><strong>Trial registration: </strong>Registration number in Prospero CRD42022375344 on 25 NOVEMBER 2022, retrospectively registered.</p>","PeriodicalId":9023,"journal":{"name":"BMC Pharmacology & Toxicology","volume":"24 1","pages":"59"},"PeriodicalIF":2.9,"publicationDate":"2023-11-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10625249/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71477699","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"GHB toxicokinetics and renal monocarboxylate transporter expression are influenced by the estrus cycle in rats.","authors":"Hao Wei,&nbsp;Jieyun Cao,&nbsp;Tyler Fallert,&nbsp;Su Yeo,&nbsp;Melanie A Felmlee","doi":"10.1186/s40360-023-00700-y","DOIUrl":"10.1186/s40360-023-00700-y","url":null,"abstract":"<p><strong>Background: </strong>The illicit use and abuse of gamma-hydroxybutyric acid (GHB) occurs due to its sedative/hypnotic and euphoric effects. Currently, there are no clinically available therapies to treat GHB overdose, and care focuses on symptom treatment until the drug is eliminated from the body. Proton- and sodium-dependent monocarboxylate transporters (MCTs (SLC16A) and SMCTs (SLC5A)) transport and mediate the renal clearance and distribution of GHB. Previously, it has been shown that MCT expression is regulated by sex hormones in the liver, skeletal muscle and Sertoli cells. The focus of the current study is to evaluate GHB toxicokinetics and renal monocarboxylate transporter expression over the estrus cycle in females, and in the absence of male and female sex hormones.</p><p><strong>Methods: </strong>GHB toxicokinetics and renal transporter expression of MCT1, SMCT1 and CD147 were evaluated in females over the estrus cycle, and in ovariectomized (OVX) female, male and castrated (CST) male rats. GHB was administered iv bolus (600 and 1000 mg/kg) and plasma and urine samples were collected for six hours post-dose. GHB concentrations were quantified using a validated LC/MS/MS assay. Transporter mRNA and protein expression was quantified by qPCR and Western Blot.</p><p><strong>Results: </strong>GHB renal clearance and AUC varied between sexes and over the estrus cycle in females with higher renal clearance and a lower AUC in proestrus females as compared to males (intact and CST), and OVX females. We demonstrated that renal MCT1 membrane expression varies over the estrus cycle, with the lowest expression observed in proestrus females, which is consistent with the observed changes in GHB renal clearance.</p><p><strong>Conclusions: </strong>Our results suggest that females may be less susceptible to GHB-induced toxicity due to decreased exposure resulting from increased renal clearance, as a result of decreased renal MCT1 expression.</p>","PeriodicalId":9023,"journal":{"name":"BMC Pharmacology & Toxicology","volume":"24 1","pages":"58"},"PeriodicalIF":2.9,"publicationDate":"2023-11-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10623699/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71420467","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction: Glucagon-like peptide receptor agonists attenuate advanced glycation end products-induced inflammation in rat mesangial cells.","authors":"Jui-Ting Chang,&nbsp;Yao-Jen Liang,&nbsp;Chia-Yu Hsu,&nbsp;Chao-Yi Chen,&nbsp;Po-Jung Chen,&nbsp;Yi-Feng Yang,&nbsp;Yen-Lin Chen,&nbsp;Dee Pei,&nbsp;Jin-Biou Chang,&nbsp;Jyh-Gang Leu","doi":"10.1186/s40360-023-00688-5","DOIUrl":"10.1186/s40360-023-00688-5","url":null,"abstract":"","PeriodicalId":9023,"journal":{"name":"BMC Pharmacology & Toxicology","volume":"24 1","pages":"57"},"PeriodicalIF":2.9,"publicationDate":"2023-10-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10612259/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"61560773","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}