BMC Pharmacology & Toxicology最新文献

{"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}

{"title":"Oxidative stress induction by narasin augments doxorubicin's efficacy in osteosarcoma.","authors":"Zhaoming Han, Juguang Yang, Ping Wang, Feng Bian, Jiguang Jia","doi":"10.1186/s40360-023-00695-6","DOIUrl":"10.1186/s40360-023-00695-6","url":null,"abstract":"<p><p>Complications and fata toxicity induced by chemotherapy are the main challenge for clinical management of osteosarcoma. The identification of agents that can augment the efficacy of chemotherapy at lower doses may represent an alternative therapeutic strategy. Narasin is a polyether antibiotic widely used in veterinary medicine. In this study, we show that narasin is active against osteosarcoma cells at the same concentrations that are less toxic to normal cells. This effect is achieved by growth inhibition and apoptosis induction, which is mediated by oxidative stress and damage, and mitochondrial dysfunction. The antioxidant N-acetyl-l-cysteine (NAC) abolishes the anti-osteosarcoma activity. Importantly, narasin significantly augments doxorubicin's efficacy in both osteosarcoma cell culturing system and subcutaneous implantation mouse model. The combination of narasin and doxorubicin at non-toxic doses completely arrests osteosarcoma growth in mice. Our results suggest that the concurrent administration of doxorubicin and narasin could present a viable alternative therapeutic approach for osteosarcoma.</p>","PeriodicalId":9023,"journal":{"name":"BMC Pharmacology & Toxicology","volume":"24 1","pages":"56"},"PeriodicalIF":2.9,"publicationDate":"2023-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10588065/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49674063","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: Core decompression combined with local DFO administration loaded on polylactic glycolic acid scaffolds for the treatment of osteonecrosis of the femoral head: a pilot study.","authors":"Kaveh Gharanizadeh, Ali Mohammad Sharifi, Hamed Tayyebi, Razieh Heidari, Shayan Amiri, Sajad Noorigaravand","doi":"10.1186/s40360-023-00691-w","DOIUrl":"10.1186/s40360-023-00691-w","url":null,"abstract":"","PeriodicalId":9023,"journal":{"name":"BMC Pharmacology & Toxicology","volume":"24 1","pages":"55"},"PeriodicalIF":2.9,"publicationDate":"2023-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10580663/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41232192","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":"Acute toxicological evaluation of AT-533 and AT-533 gel in Sprague-Dawley rats.","authors":"Lishan Zhong, Yanting Wu, Chen Huang, Kaisheng Liu, Cui-Fang Ye, Zhe Ren, Yifei Wang","doi":"10.1186/s40360-023-00696-5","DOIUrl":"10.1186/s40360-023-00696-5","url":null,"abstract":"<p><strong>Background: </strong>AT-533 is a novel heat shock protein 90 inhibitor that exerting anti-inflammatory, antiviral, and antitumor efficacy. Furthermore, the gel made of AT-533 as raw material named AT-533 gel has the function of repairing keratitis and dermatitis caused by herpes virus infection. However, the acute safety evaluation of AT-533 and AT-533 gel has not been conducted.</p><p><strong>Methods and results: </strong>Herein, we performed acute toxicological studies of AT-533 and AT-533 gel in Sprague-Dawley rats. Fifteen-day acute toxicity study of AT-533 was conducted in both male and female Sprague-Dawley rats at doses of 5, 50, 250 and 500 mg/kg and AT-533 gel at 5 g/kg in the study. During experiment, food consumption and mortality were observed and body weight, hematology, serum biochemistry and histopathological assessment of rats were carried out. No abnormal changes were observed in rats percutaneously treated with AT-533 at 5 mg/kg and 50 mg/kg and AT-533 gel. However, loss of appetite and body weight, adverse reactions, toxicologically relevant alterations in hematology and biochemistry were found in rats percutaneously treated with AT-533 at 250 mg/kg and 500 mg/kg during 15-day acute dermic toxicity study.</p><p><strong>Conclusions: </strong>The aforementioned results suggested that the LD₅₀ of AT-533 is 228.382 mg/kg and the LD₅₀ of AT-533 gel is greater than 5 g/kg. These findings indicated that AT-533 is non-toxic in rats when the dose less than 50 mg/kg and AT-533 gel can be considered a gel with no toxicity at doses less than 5 g/kg.</p>","PeriodicalId":9023,"journal":{"name":"BMC Pharmacology & Toxicology","volume":"24 1","pages":"54"},"PeriodicalIF":2.9,"publicationDate":"2023-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10576390/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41190492","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":"Retraction Note: The teratogenic effect of pregabalin on heart, liver and kidney in rats: a light microscopic, electron microscopic and immunohistochemical study.","authors":"Omnia I Ismail, Eman S Shaltout, Nora Z Abdellah, Diab F Hetta, Wael M A Abd El-Ghani, Lobna A Abdelzaher, Ahmed Mohamed Mohamed Mahmoud, Asmaa M Hasan, Noha A Rashed, Noha Esmael Ebrahem","doi":"10.1186/s40360-023-00697-4","DOIUrl":"10.1186/s40360-023-00697-4","url":null,"abstract":"","PeriodicalId":9023,"journal":{"name":"BMC Pharmacology & Toxicology","volume":"24 1","pages":"53"},"PeriodicalIF":2.9,"publicationDate":"2023-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10571280/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41190495","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":"Metformin alleviates adriamycin resistance of osteosarcoma by declining YY1 to inhibit MDR1 transcriptional activity.","authors":"Bowen Wu, Peng Li, Eryue Qiu, Jian Chen","doi":"10.1186/s40360-023-00685-8","DOIUrl":"10.1186/s40360-023-00685-8","url":null,"abstract":"<p><p>Chemotherapy resistance hinders the successful treatment of osteosarcoma (OS) to some extent. Previous studies have confirmed that metformin (Met) enhances apoptosis induced by chemotherapeutic drugs, but the underlying mechanism remains unclear. To establish adriamycin (ADM)-resistant MG-63 (MG-63/ADM) cells, the dosage of ADM was progressively increased. The results of qRT-PCR and Western blotting demonstrated that the expression level of Yin Yang 1 (YY1) and multi-drug resistance-1 (MDR1) in MG-63/ADM cells were remarkably increased compared with those in MG-63 cells. Met dramatically enhanced ADM cytotoxicity and accelerated apoptosis of MG-63/ADM cells. Moreover, Met suppressed the expressions of YY1 and MDR1 in MG-63/ADM cells. YY1 promoted its transcriptional expression by directly binding to the MDR1 promoter. Furthermore, the effects of Met on ADM sensitivity in MG-63/ADM cells was reversed due to overexpression of YY1 or MDR1. Collectively, these findings suggested that Met inhibited YY1/MDR1 pathway to reverse ADM resistance in OS, providing a new insight into the mechanism of Met in ADM resistance of OS.</p>","PeriodicalId":9023,"journal":{"name":"BMC Pharmacology & Toxicology","volume":"24 1","pages":"50"},"PeriodicalIF":2.9,"publicationDate":"2023-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10571298/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41190494","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 effectiveness and safety of botulinum toxin injections for the treatment of sialorrhea with Parkinson's disease: a systematic review and meta-analysis.","authors":"Chun-Lan Yang, Jia-Peng Huang, Ying-Chao Tan, Ting-Ting Wang, Han Zhang, Yun Qu","doi":"10.1186/s40360-023-00694-7","DOIUrl":"10.1186/s40360-023-00694-7","url":null,"abstract":"<p><strong>Background: </strong>Botulinum toxin (BoNT) injection is an important adjunctive method to treat sialorrhea. The purpose of this systematic review was to analyze the effect and safety of BoNT injections in the intervention of sialorrhea with Parkinson's disease (PD).</p><p><strong>Methods: </strong>We searched PubMed, Web Of Science (WOS), Scopus, Cochrane CENTRAL, and Embase from inception until April 2022. Randomized controlled trials or randomized crossover trials comparing BoNT with placebo in sialorrhea with PD were eligible. PRISMA guidelines were used to carry out the meta-analysis. The Drooling Severity Frequency Scale (DSFS) score and the number of adverse events (AEs) were the primary and secondary outcomes, respectively. Standardized mean differences (SMDs) and risk differences (RDs) are used to express continuous and categorical outcomes, respectively. Heterogeneity among these studies was evaluated using I² tests. We used the GRADE tool to assess the certainty of evidence (COE).</p><p><strong>Results: </strong>Eight articles involving 259 patients compared BoNT injections with a placebo for PD with sialorrhea. This meta-analysis showed a significant reduction in DSFS scores between BoNT injections and placebo (SMD=-0.98; 95% CI, -1.27 to 0.70, p<0.001; COE: high). This meta-analysis showed a significant difference in AEs between BoNT injections and placebo (RD=0.15; 95% CI, 0.05 to 0.24, p=0.002; COE: low).</p><p><strong>Conclusions: </strong>The pooled results suggest that BoNT injections have some effect on DSFS scores with sialorrhea caused by PD. There are also mild adverse events, which generally recover within a week or so. The results indicate that BoNT injection is one of the treatments for sialorrhea caused by PD, but we need to pay attention to adverse events. In addition, the follow-up time was extended to observe oral hygiene, ulceration or dental caries, and digestive function.</p><p><strong>Trial registration: </strong>Our review protocol was registered on PROSPERO (42021288334).</p>","PeriodicalId":9023,"journal":{"name":"BMC Pharmacology & Toxicology","volume":"24 1","pages":"52"},"PeriodicalIF":2.9,"publicationDate":"2023-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10571401/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41190496","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":"Dermal effects and pharmacokinetic evaluation of the lidocaine/prilocaine cream in healthy Chinese volunteers.","authors":"Lingjun Li, Baole Cai, Hongyang Li, Jun Wei, Lei Tao, Pengcheng Ma","doi":"10.1186/s40360-023-00690-x","DOIUrl":"10.1186/s40360-023-00690-x","url":null,"abstract":"<p><strong>Background: </strong>EMLA cream is a local anesthetic. The pharmacokinetics and dermal effects of a topical anesthetic formulation has not been evaluated in healthy Chinese volunteers.</p><p><strong>Materials and methods: </strong>The Pharmacokinetics of the lidocaine/prilocaine test (T) or reference (R, EMLA) cream were evaluated in a fasting, single-dose, two-period crossover bioequivalent study conducted in 40 healthy Chinese volunteers. Meanwhile, the dermal effects including blanching, erythema, temperature sensation, edema, and skin rash were also evaluated during the study.</p><p><strong>Results: </strong>After applied 15 g of the cream for 4 h to a 100 cm² area under plastic occlusive film on the skin of the thigh of healthy volunteers, the results of the pharmacokinetic study showed that the active components absorbed in skin from topical products was relatively low compared with most system absorption drugs. After the removal of the residual anesthetic cream, there was a vascular biphasic response with initial transient blanching which reaches a peak at 4.5 h and later more persisting period erythema. The change of temperature sensory sensitivity reached the peak value at 4.5-6 h.There was no statistically significant difference of the changes after application the lidocaine/prilocaine T or R cream in subjects. In general, the lidocaine/prilocaine T or R cream was well tolerated.</p><p><strong>Conclusion: </strong>The method described a model for investigations of pharmacokinetics and pharmacodynamics of topical lidocaine/prilocaine cream. Except the plasma drug level indicator, these pharmacodynamics data should also be evaluated in the anesthetic transdermal pharmacokinetics study.</p><p><strong>Clinical trial registration: </strong>CTR20211544; registered in http://www.chinadrugtrials.org.cn/ at September 2021.</p>","PeriodicalId":9023,"journal":{"name":"BMC Pharmacology & Toxicology","volume":"24 1","pages":"51"},"PeriodicalIF":2.9,"publicationDate":"2023-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10571248/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41190493","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}