BMC Pharmacology & Toxicology最新文献

{"title":"A real-world disproportionality analysis of the US Food and Drug Administration (FDA) adverse event reporting system (FAERS) events for Durvalumab.","authors":"Ting Zou, Zhuoyang Li, Tianhong Wang, Shuang Deng, Siman Wang, Yusi Hua","doi":"10.1186/s40360-024-00821-y","DOIUrl":"10.1186/s40360-024-00821-y","url":null,"abstract":"<p><strong>Background: </strong>In the past few years, an increasing number of research studies have documented the utilization of durvalumab in the field of immunotherapy for cancerous tumors. However, there remains insufficient documentation regarding its associated adverse event (AEs). In order to enhance our comprehension of its toxicological profile, this investigation retrospectively examined the AEs linked to durvalumab using data from the US Food and Drug Administration adverse event reporting system (FAERS).</p><p><strong>Methods: </strong>Using data from FAERS for the period 2004 to 2024, the reporting odds ratio (ROR), proportional reporting ratio (PRR), Bayesian confidence propagation neural network (BCPNN) and mu-item gamma Poisson shrinker (MGPS) four algorithms were used to quantify durvalumab related AEs. SAS 9.4 was used for statistical analysis.</p><p><strong>Results: </strong>We collected nonduplicated reported 17,629,340 patients from the FAERS database and 19,709 AEs cases in the target population with durvalumab as the primary drug of suspicion. There were 6 significantly disproportionate preferred terms (PTs) that fit all four algorithms simultaneously. The AEs commonly reported include death, radiation pneumonitis, pneumonitis, and lung disorders. Furthermore, durvalumab has been associated with additional AEs, such as metastases to the central nervous system and drug-induced liver injury.</p><p><strong>Conclusions: </strong>The study revealed that durvalumab immunotherapy is associated with AEs including death, radiation pneumonitis, pneumonitis, metastases to the central nervous system, lung disorder and drug-induced liver injury. In clinical practice, it is crucial to be vigilant and prevent the occurrence of these AEs.</p>","PeriodicalId":9023,"journal":{"name":"BMC Pharmacology & Toxicology","volume":"25 1","pages":"97"},"PeriodicalIF":2.8,"publicationDate":"2024-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11657981/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142852413","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":"Eco-friendly green synthesis of silver nanoparticles from guajava leaves extract for controlling organophosphorus pesticides hazards, characterization, and in-vivo toxicity assessment.","authors":"Emad Ali Albadawi, Eid Nassar Ali Musa, Hadel Mahroos Ghaban, Neven A Ebrahim, Muayad Saud Albadrani, Ahmed I El-Tokhy","doi":"10.1186/s40360-024-00826-7","DOIUrl":"10.1186/s40360-024-00826-7","url":null,"abstract":"<p><p>This study explores an eco-friendly approach to mitigate risks associated with organophosphorus insecticides, particularly Chlorpyrifos, by synthesizing silver nanoparticles (AgNPs) using Psidium guajava leaf extract and preparing a nanocomposite (AgNPs/S18) with Chlorpyrifos pesticide. The green-synthesized AgNPs and AgNPs/S18 nanocomposite were characterized using various analytical techniques, confirming the successful synthesis of AgNPs with an average size of 37 nm and forming a stable nanocomposite. Antibacterial assays demonstrated significant activity against Staphylococcus aureus, with AgNPs showing an 87.8% reduction and the nanocomposite achieving a 72% reduction in bacterial population. Cytotoxicity evaluations on normal liver and liver cancer cell lines revealed enhanced cytotoxicity of the nanocomposite compared to AgNPs alone, suggesting potential applications in targeted therapies. In vivo studies on rats revealed the protective effects of AgNPs and the nanocomposite against Chlorpyrifos-induced toxicity in liver and kidney tissues. Histopathological and ultrastructural analyses showed both treatments, particularly the nanocomposite, significantly mitigated cellular damage caused by Chlorpyrifos exposure. These findings suggest that green-synthesized AgNPs and their nanocomposite with Chlorpyrifos offer a promising approach to reducing pesticide hazards while maintaining efficacy. This research contributes to developing safer alternatives in pest management, addressing the need for more environmentally friendly agricultural practices while protecting human health and ecosystems.</p>","PeriodicalId":9023,"journal":{"name":"BMC Pharmacology & Toxicology","volume":"25 1","pages":"98"},"PeriodicalIF":2.8,"publicationDate":"2024-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11658244/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142852415","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 vildagliptin versus metformin on hepatic steatosis in type 2 diabetic patients: a randomized controlled trial.","authors":"Asmaa S Mohamed, Hosam M Ahmad, Mohammed A Sharawy, Fatma M M Kamel","doi":"10.1186/s40360-024-00818-7","DOIUrl":"10.1186/s40360-024-00818-7","url":null,"abstract":"<p><strong>Background: </strong>The risk of hepatic steatosis (HS) is elevated in patients with type 2 diabetes mellitus (T2D). Antidiabetic medications may contribute to the prevention or treatment of HS. This study aimed to compare the effects of vildagliptin and metformin on hepatic steatosis in newly diagnosed T2D patients, using the Hepatic Steatosis Index (HSI) and ultrasound grading.</p><p><strong>Methods: </strong>The study included 246 newly diagnosed T2D patients who were randomly assigned to two groups. The first group (117 patients) received 50 mg of vildagliptin orally twice daily. The second group (129 patients) received 500 mg of metformin orally twice daily with meals, and the dosage could be gradually increased by 500 mg per week, up to a maximum daily dose of 2000 mg. Baseline and 6-month follow-up assessments included fasting blood glucose (FBG), HbA1c, weight, body mass index (BMI), waist circumference (WC), hip circumference (HC), the Hepatic Steatosis Index (HSI), and hepatic steatosis grading via ultrasound.</p><p><strong>Results: </strong>Both groups showed significant improvements in FBG, HbA1c, weight, BMI, WC, HC, HSI, and ultrasound grading of hepatic steatosis from baseline to the 6-month follow-up (p < 0.001). The metformin group demonstrated significantly greater reductions in weight and BMI compared to the vildagliptin group (p = 0.001 and p = 0.009, respectively). However, there was no significant difference between the two groups in terms of hepatic steatosis improvement on ultrasound. Correlation analysis revealed that HSI was significantly associated with HbA1c, BMI, WC, and HC (p < 0.001 for all), as well as FBG (p = 0.008), but not with age. The lipid profile, particularly total cholesterol and LDL, was identified as a stronger predictor of hepatic steatosis, based on high AUC, sensitivity, and specificity values.</p><p><strong>Conclusion: </strong>Both vildagliptin and metformin are effective in improving glycemic control in newly diagnosed T2D patients, as evidenced by reductions in FBG and HbA1c levels. Additionally, both drugs significantly reduced the HSI, body weight, and BMI, with metformin showing a more pronounced effect on weight and BMI. Both vildagliptin and metformin effectively decreased hepatic steatosis in T2D patients. Total cholesterol and LDL are important predictors of hepatic steatosis.</p><p><strong>Trial registration: </strong>Trial Registration ID: UMIN000055121, registered on 30/07/2024 (retrospectively registered).</p>","PeriodicalId":9023,"journal":{"name":"BMC Pharmacology & Toxicology","volume":"25 1","pages":"94"},"PeriodicalIF":2.8,"publicationDate":"2024-12-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11645785/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142821788","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 comparison of the effects of ticagrelor and clopidogrel in patients with acute ST-segment elevation myocardial infarction: a systematic review and meta-analysis of randomized clinical trials.","authors":"Mehdi Geravandi, Mohammad Nourabi, Sepehr Navabifar, Moein Geravandi, Zahra Hooshanginezhad, Sara Zand, Parinaz Taheri","doi":"10.1186/s40360-024-00817-8","DOIUrl":"10.1186/s40360-024-00817-8","url":null,"abstract":"<p><strong>Background: </strong>Rupture of unstable coronary atherosclerotic plaque leads to acute ST-segment elevation myocardial infarction (STEMI). Dual anti-platelet therapy is one of the main treatments, and the combination of Aspirin and Clopidogrel is recognized as the standard oral regimen in most cases. Ticagrelor is a new generation of P2Y12 receptor inhibitors. We aimed to compare the effect of Ticagrelor and Clopidogrel in the treatment of patients post-STEMI.</p><p><strong>Methods: </strong>This study investigated Pub Med, Scopus, Google Scholar Web of Science, and Embase Cochrane Library clinical trials.gov databases. Heterogeneity between studies was assessed using the I2 index and the Q statistic. The random effects model was used to combine studies and the Funnel plot and Egger's test were used to assess the publication bias.</p><p><strong>Results: </strong>Eleven studies were included in this meta-analysis. 5274 patients in the Ticagrelor and 5,295 patients in the Clopidogrel groups were examined. The mean age of the patients was 58.84 years (2.70) and 59.92 years (3.19) in the Ticagrelor and Clopidogrel groups, respectively. Based on the results of the meta-analysis, compared to Clopidogrel, Ticagrelor had decreased the outcomes of mortality, recurrent myocardial infarction, stroke, and Major Adverse Cardiovascular Events (MACE). However, the post-myocardial infarction bleeding according to Bleeding Academic Research Consortium (BARC) criteria and reperfusion state regarding thrombolysis in myocardial infarction (TIMI) Flow Grading system showed no differences in both groups. However, these effects were not statistically significant.</p><p><strong>Conclusions: </strong>Ticagrelor decreased the chance of mortality, re-infarction, stroke, and MACE in post-STEMI patients compared to clopidogrel. But there was no difference in the chance of major bleedings (BARC ≥ 3) and improvement in TIMI grade flow between these two drugs. However, none of these findings were statistically significant, and more studies are needed to reach definitive results.</p>","PeriodicalId":9023,"journal":{"name":"BMC Pharmacology & Toxicology","volume":"25 1","pages":"93"},"PeriodicalIF":2.8,"publicationDate":"2024-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11626762/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142799368","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":"Toxicology study of a tissue anchoring paclitaxel prodrug.","authors":"Rukesh Chinthapatla, Jazz Q Stephens, Isabel B Neumann-Rivera, Nichol M Henderson, Minhua Nie, Hannah R Haynes, Joshua G Pierce, Danielle M Meritet, Yevgeny Brudno, Annie Oh","doi":"10.1186/s40360-024-00819-6","DOIUrl":"10.1186/s40360-024-00819-6","url":null,"abstract":"<p><strong>Background: </strong>Local drug presentation made possible by drug-eluting depots provides benefits for a vast array of diseases, including cancer, microbial infection, and wound healing. Drug-eluting depots provide sustained drug release of therapeutics directly at disease sites with tunable kinetics, remove the need for drugs to access disease sites from circulation, and reduce the side effects associated with systemic therapy. Recently, we introduced an entirely novel approach to local drug presentation named Tissue-Reactive Anchoring Pharmaceuticals (TRAPs). TRAPs enables local drug presentation without any material carriers, capitalizing on innate tissue structures to anchor drugs at the site of administration.</p><p><strong>Methods: </strong>In this report, we comprehensively evaluate the local and systemic toxicological profile of a paclitaxel version of TRAPs in mice by clinical observations, body weight monitoring, histopathological evaluations of injection sites and major organs, as well as blood and urine analyses.</p><p><strong>Results: </strong>We find that intradermal administration of TRAP-paclitaxel does not induce substantial toxic effects. Localized inflammatory responses were observed at the injection sites and secondary minimal, non-specific inflammation was observed in the liver. All other organs displayed unremarkable histological findings.</p><p><strong>Conclusions: </strong>These findings support the potential of TRAP-paclitaxel as a promising candidate for localized cancer treatment, offering high-concentration drug delivery while mitigating scarring and adverse side effects.</p>","PeriodicalId":9023,"journal":{"name":"BMC Pharmacology & Toxicology","volume":"25 1","pages":"92"},"PeriodicalIF":2.8,"publicationDate":"2024-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11619278/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142783845","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":"Comparison of the prophylactic effect of cefazolin injection versus oral levofloxacin as prophylactic antibiotic in TURP surgery: a randomized clinical trial.","authors":"Ramin Haghighi, Ahmad Kameli, Abdolah Razi, Dorsa Abroon, Amir Amani","doi":"10.1186/s40360-024-00814-x","DOIUrl":"10.1186/s40360-024-00814-x","url":null,"abstract":"<p><strong>Introduction: </strong>Use of antibiotic prophylaxis before transurethral resection of the prostate (TURP) is highly recommended. However, there is no agreement on the use of a single antibiotic for this purpose. This study aimed to compare the prophylactic effect of cefazolin injection with oral levofloxacin on postoperative complications in TURP surgery.</p><p><strong>Trial design: </strong>Body temperature and urine culture results were obtained two and five days after surgery. Drugs' side effects as well as surgery and catheterization time were also recorded.</p><p><strong>Methods: </strong>In an analytical-comparative trial, the participants were randomly divided into two groups to receive cefazolin or levofloxacin before the surgery.</p><p><strong>Results: </strong>The duration of surgery (min) and catheterization (days) were 41.5 ± 11.7 and 4.7 ± 1.8 for levofloxacin-treated group and 43.9 ± 11.9 and 4.7 ± 1.8 for cefazolin-treated group, respectively. The number of positive urine cultures, 2 and 5 days post-surgery were 12 and 14 for levofloxacin-treated group and 9 and 12 for cefazolin-treated group, respectively. Furthermore, both groups reported one fever two days after surgery and had no fever after 5 days. In total, no significant difference was observed between the two groups. Additionally, no correlation was observed between the demographic data (i.e. age, BMI and prostate volume) and the postoperative complications (i.e. fever and urinary culture tests), except between age and urinary culture 2 days after the surgery.</p><p><strong>Conclusion: </strong>Considering the lack of significant differences between the two groups, the use of oral levofloxacin is suggested as an easy to take and cost-effective alternative to injection of cefazolin before TURP surgery.</p><p><strong>Trial registration: </strong>Iranian registry of clinical trials, IRCT registration number IRCT20160514027893N4, available through www.irct.ir , Registration date: 2024-03-13 (Retrospectively registered).</p>","PeriodicalId":9023,"journal":{"name":"BMC Pharmacology & Toxicology","volume":"25 1","pages":"91"},"PeriodicalIF":2.8,"publicationDate":"2024-12-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11610085/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142765881","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":"Effects of melatonin on the prevention of delirium in hospitalized older patients: systematic review and meta-analysis.","authors":"Le Liu, Xin Ma, Zejun Song, Jie Li, Yasong Zhao, Chang Meng, Shufang Wang, Guobin Miao, Peng Liu","doi":"10.1186/s40360-024-00816-9","DOIUrl":"10.1186/s40360-024-00816-9","url":null,"abstract":"<p><strong>Objectives: </strong>Melatonin has been demonstrated to exert a preventive effect on delirium. This meta-analysis sought to investigate the preventive effects of melatonin and melatonin receptor agonists (ramelteon) on delirium in hospitalized elderly patients.</p><p><strong>Methods: </strong>This systematic review and meta-analysis delineates the risk of delirium events in older hospitalized patients with melatonin/ramelteon compared with placebo, incorporating randomized controlled trials published up to 8 July 2024. The databases searched were PubMed, Embase and the Cochrane Library. The primary outcome measures were the incidence of delirium, while the secondary outcome measures were the length of hospital stay and mortality. The results are presented as odds ratios (OR) or mean differences (MD) with a 95% confidence interval. The review of publications was conducted in accordance with the guidelines set forth in the Cochrane Handbook and the Preferred Reporting Project for Systematic Review and Meta-Analysis (PRISMA). This study has been registered with INPLASY (number INPLASY202470044).</p><p><strong>Results: </strong>A total of 2086 patients were included in 13 randomized controlled trials. The primary outcome of this meta-analysis demonstrated a statistically difference in the incidence of delirium between the melatonin and placebo groups in hospitalized elderly patients (OR = 0.59, 95% CI: 0.40-0.87, P < 0.01, I² = 60%), particularly in those who had undergone surgery (OR = 0.60, 95%CI: 0.40-0.89, P = 0.01, I² = 53%). No statistically differences were observed in terms of length of stay (MD=-0.07, 95%CI:-1.09-0.94, P = 0.89, I² = 72%) and mortality (OR = 0.79, 95%CI:0.58-1.06, P = 0.12, I² = 0%).</p><p><strong>Conclusions: </strong>Melatonin has been demonstrated to exert a protective effect on delirium in elderly patients who are hospitalized, particularly in the context of perioperative care.</p>","PeriodicalId":9023,"journal":{"name":"BMC Pharmacology & Toxicology","volume":"25 1","pages":"90"},"PeriodicalIF":2.8,"publicationDate":"2024-11-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11587658/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142715061","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":"Pulrodemstat, a selective inhibitor of KDM1A, suppresses head and neck squamous cell carcinoma growth by triggering apoptosis.","authors":"Cheng Jiang, Xiaofeng Weng, Yuqing Chen, Junjun Yang","doi":"10.1186/s40360-024-00807-w","DOIUrl":"10.1186/s40360-024-00807-w","url":null,"abstract":"<p><strong>Background: </strong>Chemotherapy is often ineffective as a first-line treatment for head and neck squamous cell carcinoma (HNSCC), and a more precise and effective therapeutic option is urgently needed.</p><p><strong>Methods: </strong>High-throughput screening of a histone demethylase inhibitor library was performed to identify potential drugs for treating HNSCC. The Cancer Genome Atlas (TCGA) and single-cell sequencing were used to evaluate the potential diagnostic value and expression distribution of candidate drug targets. Colony formation, transwell assays, and flow cytometry analyses were used to assess the antitumor function of the potential drugs. The CCK-8 assay was used to compare the antitumor activity of the candidate drug and the traditional chemotherapy drug. Bioinformatic analysis based on TCGA database was used for unveiling the upstream signaling.</p><p><strong>Results: </strong>Pulrodemstat, a selective KDM1A inhibitor that is ongoing clinical trial, stood out as the most effective candidate anti-HNSCC drug based on the high-throughput screening. IC₅₀ analysis revealed that Pulrodemstat might possess stronger anti-tumor activity than 5-Fu. Additionally, Pulrodemstat dramatically suppressed HNSCC cell proliferation and migration without inducing toxicity in normal cells. TCGA analysis revealed that KDM1A is positively associated with tumor proliferation, DNA repair, and DNA replication in HNSCC. Consistent with these results, Pulrodemstat substantially induced apoptosis in the HNSCC cells. Furthermore, TCGA analysis revealed that KDM1A was aberrantly overexpressed in HNSCC, positively correlated with malignancy, and negatively associated with the clinical outcomes of HNSCC patients. Notably, single-cell analysis indicated that KDM1A was mainly distributed in the malignant cells of HNSCC samples, highlighting that Pulrodemstat may be a more precise therapeutic option for HNSCC. In addition, methylation occupancies in the KDM1A promoter were substantially low in HNCC tumors, and low methylation occupancies in the KDM1A promoter predicted poor clinical outcomes in HNSCC. These data are consistent with the KDM1A expression in HNSCC. Moreover, TET3, a DNA demethylase, was strongly and positively correlated with KDM1A expression.</p><p><strong>Conclusions: </strong>Pulrodemstat is an effective therapeutic drug for HNSCC. Thus, the TET3/KDM1A axis may account for the malignant phenotype of HNSCC.</p>","PeriodicalId":9023,"journal":{"name":"BMC Pharmacology & Toxicology","volume":"25 1","pages":"89"},"PeriodicalIF":2.8,"publicationDate":"2024-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11580532/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142680563","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":"Resveratrol inhibits ferroptosis in the lung tissues of heat stroke-induced rats via the Nrf2 pathway.","authors":"Liwen Du, Xueqi Zhu, Zhenluo Jiang, Weidong Wang, Peng Liu, Leilei Zhu, Fangqi Zhang","doi":"10.1186/s40360-024-00810-1","DOIUrl":"10.1186/s40360-024-00810-1","url":null,"abstract":"<p><strong>Background: </strong>Heat stroke (HS) can lead to the development of pulmonary ferroptosis. The inhibition of pulmonary ferroptosis during HS improves patient prognosis. The aim of this study was to investigate the effects of resveratrol (RES) on heat stress at an ambient temperature of 42 °C.</p><p><strong>Methods: </strong>Heat stress was induced in Beas-2B cells and lung injury was induced in HS rats at an ambient temperature of 42 °C. The anti-oxidative stress and anti-ferroptotic effects of RES were confirmed through tail vein injection of nuclear factor-2 associated factor (Nrf2) shRNA recombinant adeno-associated virus 6 (AAV6-shNrf2).</p><p><strong>Results: </strong>RES treatment attenuated the upregulation of reactive oxygen species (ROS) and malondialdehyde (MDA) levels and alleviated glutathione inhibition in HS. In addition, RES treatment reduced the accumulation of Fe²⁺ in heat-stressed Beas-2B cells and increased the ferroptosis resistance-related proteins FTH1, GPX4, and SLC7A11 as well as the anti-oxidative stress pathway proteins Nrf2, NQO1, and HO-1. The antioxidant and anti-ferroptotic effects of RES in heat-stressed Beas-2B cells were effectively reversed upon treatment with Nrf2-IN-1, an Nrf2 pathway inhibitor. In the HS rat model, the antioxidant and anti-ferroptotic effects of RES were reversed by an ambient temperature of 42 °C and relative humidity of 60 ± 5%.</p><p><strong>Conclusions: </strong>RES effectively protected HS rats from lung injury, inhibited the accumulation of Fe²⁺, ROS, and MDA in the lung, and upregulated FTH1, GPX4, SLC7A11, Nrf2, NQO1, and HO-1.</p>","PeriodicalId":9023,"journal":{"name":"BMC Pharmacology & Toxicology","volume":"25 1","pages":"88"},"PeriodicalIF":2.8,"publicationDate":"2024-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11577854/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142674975","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":"An in vivo and in silico probing of the protective potential of betaine against sodium fluoride-induced neurotoxicity.","authors":"Solomon E Owumi, Bayode J Oluwawibe, Joseph Chimezie, Jesutosin J Babalola, Oludare M Ogunyemi, Gideon A Gyebi, Moses T Otunla, Ahmad Altayyar, Uche O Arunsi, Chioma E Irozuru, Olatunde O Owoeye","doi":"10.1186/s40360-024-00812-z","DOIUrl":"10.1186/s40360-024-00812-z","url":null,"abstract":"<p><p>Excessive fluoride exposure beyond the tolerable limit may adversely impacts brain functionality. Betaine (BET), a trimethyl glycine, possesses antioxidant, anti-inflammatory and anti-apoptotic functions, although the underlying mechanisms of the role of BET on fluoride-induced neurotoxicity remain unelucidated. To assess the mechanism involved in the neuro-restorative role of BET on behavioural, neurochemical, and histological changes, we employed a rat model of sodium fluoride (NaF) exposure. Animals were treated with NaF (9 mg/kg) body weight (bw) only or co-treated with BET (50 and 100 mg/kg bw) orally uninterrupted for 28 days. We obtained behavioural phenotypes in an open field, performed negative geotaxis, and a forelimb grip test, followed by oxido-inflammatory, apoptotic, and histological assessment. Behavioural endpoints indicated lessened locomotive and motor and heightened anxiety-like performance and upregulated oxidative, inflammatory, and apoptotic biomarkers in NaF-exposed rats. Co-treatment with BET significantly enhanced locomotive, motor, and anxiolytic performance, increased the antioxidant signalling mechanisms and demurred oxidative, inflammatory, and apoptotic biomarkers and histoarchitectural damage in the cerebrum and cerebellum cortices mediated by NaF. The in-silico analysis suggests that multiple hydrogen bonds and hydrophobic interactions of BET with critical amino acid residues, including arginine (ARG380 and ARG415) in the Keap1 Kelch domain, which may disrupt Keap1-Nrf2 complex and activate Nrf2. This may account for the observed increased in the Nrf2 levels, elevated antioxidant response and enhanced anti-inflammatory response. The BET-Keap1 complex was also observed to exhibit structural stability and conformational flexibility in solvated biomolecular systems, as indicated by the thermodynamic parameters computed from the trajectories obtained from a 100 ns full atomistic molecular dynamics simulation. Therefore, BET mediates neuroprotection against NaF-induced cerebro-cerebellar damage through rats' antioxidant, anti-inflammatory, and anti-apoptotic activity, which molecular interactions with Keap1-Nrf2 may drive.</p>","PeriodicalId":9023,"journal":{"name":"BMC Pharmacology & Toxicology","volume":"25 1","pages":"87"},"PeriodicalIF":2.8,"publicationDate":"2024-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11568634/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142643514","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}