BMC Pharmacology & Toxicology最新文献

{"title":"Sustain-release lipid-liquid crystal formulations of pexiganan against Helicobacter pylori infection: in vitro evaluation in C57BL/6 mice.","authors":"Kiarash Ghazvini, Hossein Kamali, Hadi Farsiani, Masoud Yousefi, Masoud Keikha","doi":"10.1186/s40360-024-00731-z","DOIUrl":"10.1186/s40360-024-00731-z","url":null,"abstract":"<p><strong>Introduction: </strong>The Gram-negative bacterium Helicobacter pylori, H. pylori, is associated with significant digestive disorders. However, the effectiveness of bacterial eradication is declining due to drug resistance. A potent anti-H. pylori activity is shown by the natural antimicrobial peptide pexiganan.</p><p><strong>Objective: </strong>The current study aimed to evaluate the effectiveness of pexiganan and its lipid-liquid crystals (LLCs) in inducing Helicobacter pylori in mice.</p><p><strong>Methods: </strong>In this experimental study, H. pylori infection was first induced in C57BL/6 mice. Secondly, the antibacterial efficacy of pexiganan and its LLCs formulations was investigated to eliminate H. pylori infection.</p><p><strong>Results: </strong>The H. pylori infection could not be completely eradicated by pexiganan peptide alone. However, incorporating pexiganan within the LLC formulation resulted in an increased elimination of H. pylori. Under the H&E strain, the pexiganan-LLCs formulation revealed minimal mucosal alterations and a lower amount of inflammatory cell infiltration in the stomach compared to the placebo.</p><p><strong>Conclusion: </strong>Clarithromycin was more effective than pexiganan at all tested concentrations. Furthermore, the pexiganan-loaded LLCs exhibited superior efficacy in curing H. pylori infection in a mouse model compared to pexiganan alone. This formulation can enhance H. pylori clearance while mitigating the adverse effects, typically associated with conventional drugs, leading to a viable alternative to current treatment options.</p>","PeriodicalId":9023,"journal":{"name":"BMC Pharmacology & Toxicology","volume":"25 1","pages":"9"},"PeriodicalIF":2.9,"publicationDate":"2024-01-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10785446/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139429574","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":"Fenofibrate alleviates NAFLD by enhancing the PPARα/PGC-1α signaling pathway coupling mitochondrial function.","authors":"Xuemei Wang, Jieying Wang, Cao Ying, Yuan Xing, Xuan Su, Ke Men","doi":"10.1186/s40360-023-00730-6","DOIUrl":"10.1186/s40360-023-00730-6","url":null,"abstract":"<p><strong>Background: </strong>To comprehend the influences of fenofibrate on hepatic lipid accumulation and mitochondrial function-related signaling pathways in mice with non-alcoholic fatty liver disease (NAFLD) secondary to high-fat diets together with free fatty acids-influenced HepG2 cells model.</p><p><strong>Materials and methods: </strong>A random allocation of male 6-week C57BL/6J mice into three groups was done, including controls, model (14 weeks of a high-fat diet), and fenofibrate [similar to the model one with administered 0.04 g/(kg.d) fenofibrate by gavage at 11 weeks for 4 weeks] groups, which contained 10 mice each. This study verified NAFLD pathogenesis via mitochondrial functions in hepatic pathological abnormalities, liver index and weight, body weight, serum biochemical indexes, oxidative stress indicators, mitochondrial function indexes, and related signaling pathways. The effect of fenofibrate intervention was investigated in NAFLD model mice. In vitro, four groups based on HepG2 cells were generated, including controls, the FFA model (1.5 mmol/L FFA incubation for 24 h), LV-PGC-1α intervention (similar to the FFA model one after PPARGC1A lentivirus transfection), and LV control intervention (similar to the FFA model one after negative control lentivirus transfection) groups. The study investigated the mechanism of PGC-1α related to lipid decomposition and mitochondrial biosynthesis by Oil red O staining, colorimetry and western blot.</p><p><strong>Results: </strong>In vivo experiments, a high-fat diet achieved remarkable changes regarding liver weight, liver index, serum biochemical indicators, oxidative stress indicators, liver pathological changes, mitochondrial function indicators, and body weight of the NAFLD model mice while fenofibrate improved the objective indicators. In the HepG2 cells model, the lipid accumulation increased significantly within the FFA model group, together with aggravated hepatocytic damage and boosted oxidative stress levels. Moreover, FFA induced excessive mitosis into fragmented in mitochondrial morphology, ATP content in cells decreased, mtDNA replication fold decreased, the expression of lipid decomposition protein PPARα reduced, mitochondrial biosynthesis related protein PGC-1α, NRF-1 and TFAM decreased. PGC-1α overexpression inhibited lipid deposition by improving mitochondrial biosynthesis and lipid decomposition.</p><p><strong>Conclusion: </strong>Fenofibrate up-regulated PPARα/PGC-1α signaling pathway, promoted mitochondrial β-oxidation, reduced oxidative stress damage and lipid accumulation of liver. PGC-1α overexpression enhanced mitochondrial biosynthesis and ATP production, and reduced HepG2 intracellular accumulation of lipids and oxidative stress.</p>","PeriodicalId":9023,"journal":{"name":"BMC Pharmacology & Toxicology","volume":"25 1","pages":"7"},"PeriodicalIF":2.9,"publicationDate":"2024-01-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10765888/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139085759","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":"Amlodipine alleviates renal ischemia/reperfusion injury in rats through Nrf2/Sestrin2/PGC-1α/TFAM Pathway.","authors":"Hadi Shirzad, Seyed Amin Mousavinezhad, Mohammad Panji, Moin Ala","doi":"10.1186/s40360-023-00722-6","DOIUrl":"10.1186/s40360-023-00722-6","url":null,"abstract":"<p><strong>Background: </strong>Previously, observational studies showed that amlodipine can mitigate calcineurin inhibitor- and contrast-induced acute kidney injury (AKI). Herein, we aimed to measure the effect of amlodipine on renal ischemia/reperfusion (I/R) injury and find the underlying mechanisms.</p><p><strong>Materials and methods: </strong>Bilateral renal I/R was induced by clamping the hilum of both kidneys for 30 min. The first dose of amlodipine 10 mg/kg was gavaged before anesthesia. The second dose of amlodipine was administered 24 h after the first dose. Forty-eight hours after I/R, rats were anesthetized, and their blood and tissue specimens were collected.</p><p><strong>Results: </strong>Amlodipine significantly decreased the elevated serum levels of creatinine and blood urea nitrogen (BUN) and mitigated tissue damage in hematoxylin & eosin (H&E) staining. Amlodipine strongly reduced the tissue levels of malondialdehyde (MDA), interleukin 1β (IL1β), and tumor necrosis factor α (TNF-α). Amlodipine enhanced antioxidant defense by upregulating nuclear factor erythroid 2-related factor 2 (Nrf2) and Sestrin2. Furthermore, amlodipine significantly improved mitochondrial biogenesis by promoting Sestrin2/peroxisome proliferator-activated receptor-gamma coactivator (PGC-1α)/mitochondrial transcription factor A (TFAM) pathway. It also enhanced autophagy and attenuated apoptosis, evidenced by increased LC3-II/LC3-I and bcl2/bax ratios after renal I/R.</p><p><strong>Conclusion: </strong>These findings suggest that amlodipine protects against renal I/R through Nrf2/Sestrin2/PGC-1α/TFAM Pathway.</p>","PeriodicalId":9023,"journal":{"name":"BMC Pharmacology & Toxicology","volume":"24 1","pages":"82"},"PeriodicalIF":2.9,"publicationDate":"2023-12-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10740300/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138828073","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":"Antibiotics and antibiotic-associated diarrhea: a real-world disproportionality study of the FDA adverse event reporting system from 2004 to 2022.","authors":"Haining Huang, Lanfang Li, Mingli Wu, Zhen Liu, Yanyan Zhao, Jing Peng, Xiaolei Ren, Shuai Chen","doi":"10.1186/s40360-023-00710-w","DOIUrl":"10.1186/s40360-023-00710-w","url":null,"abstract":"<p><strong>Background: </strong>Our study aimed to assess the risk signals of antibiotic-associated diarrhea (AAD) caused by various antibiotics using real-world data and provide references for safe clinical applications.</p><p><strong>Methods: </strong>We analyzed data extracted from the FDA Adverse Event Reporting System (FAERS) database, covering the period from the first quarter of 2004 to the third quarter of 2022. We computed the reporting odds ratio (ROR) for each antibiotic or antibiotic class to compare the signal difference. Furthermore, we also examined the differences in the onset times and outcomes of AAD caused by various antibiotics.</p><p><strong>Results: </strong>A total of 5,397 reports met the inclusion requirements. Almost all antibiotics, except tobramycin and minocycline (ROR 0.98; 95%CI: 0.64-1.51 and 0.42; 95%CI: 0.16-1.11, respectively), showed a significant correlation with AAD. The analysis of the correlation between different classes of antibiotics and AAD revealed that lincomycins (ROR 29.19; 95%CI: 27.06-31.50), third-generation cephalosporins (ROR 15.96; 95%CI: 14.58-17.47), and first/second generation cephalosporins (ROR 15.29; 95%CI: 13.74-17.01) ranked the top three. The ROR values for antibiotics from the same class of antibiotics also varied greatly, with the ROR values for third-generation cephalosporins ranging from 9.97 to 58.59. There were also differences in ROR values between β-lactamase inhibitors and their corresponding β-lactamase drugs, such as amoxicillin-clavulanate (ROR = 13.31; 95%CI: 12.09-14.65) and amoxicillin (ROR = 6.50; 95%CI: 5.69-7.44). 91.35% of antibiotics have an onset time of less than four weeks.</p><p><strong>Conclusions: </strong>There is a significant correlation between almost all antibiotics and AAD, particularly lincomycins and β-lactam antibiotics, as well as a different correlation within the same class. These findings offer valuable evidence for selecting antibiotics appropriately.</p>","PeriodicalId":9023,"journal":{"name":"BMC Pharmacology & Toxicology","volume":"24 1","pages":"73"},"PeriodicalIF":2.9,"publicationDate":"2023-12-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10694877/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138481859","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 pharmacotherapies for bulimia nervosa: a systematic review and meta-analysis.","authors":"Sijie Yu, Yuhan Zhang, Chongkai Shen, Fei Shao","doi":"10.1186/s40360-023-00713-7","DOIUrl":"10.1186/s40360-023-00713-7","url":null,"abstract":"<p><strong>Objective: </strong>The main purpose was to evaluate the efficacy and tolerability of different medications used to treat bulimia nervosa (BN).</p><p><strong>Methods: </strong>Randomized controlled trials (RCTs) were identified from published sources through searches in PubMed, Cochrane Library, Web of Science, and Embase from inception to November 2022. Primary outcomes were changes in the frequency of binge eating episodes and vomiting episodes from baseline to endpoint. Secondary outcomes were differences in the improvement of scores in depressive symptoms, tolerability (dropout due to adverse events) and weight change.</p><p><strong>Results: </strong>The literature search ultimately included 11 drugs, 33 studies and 6 types of drugs, 8 trials with TCAs (imipramine, desipramine), 14 with SSRIs (fluoxetine, citalopram and fluvoxamine), 6 with MAOIs (phenelzine, moclobemide and brofaromine), 3 with antiepileptic drugs (topiramate), 1 with mood stabilizers (lithium), and 1 with amphetamine-type appetite suppressant (fenfluramine). The reduction in binge eating episodes was more likely due to these drugs than the placebo, and the SMD was -0.4 (95% CI -0.61 ~ -0.19); the changes in the frequency of vomiting episodes (SMD = -0.16, 95% CI -0.3 ~ -0.03); weight (WMD = -3.05, 95% CI -5.97 ~ -0.13); and depressive symptoms (SMD = -0.32, 95% CI -0.51 ~ -0.13). However, no significant difference was found in dropout due to adverse events (RR = 1.66, 95% CI 1.14 ~ 2.41).</p><p><strong>Conclusions: </strong>This meta-analysis indicates that most pharmacotherapies decreased the frequency of binge-eating and vomiting episodes, body weight, and depressive symptoms in BN patients, but the efficacy was not significant. In each drug the efficacy is different, treating different aspects, different symptoms to improve the clinical performance of bulimia nervosa.</p>","PeriodicalId":9023,"journal":{"name":"BMC Pharmacology & Toxicology","volume":"24 1","pages":"72"},"PeriodicalIF":2.8,"publicationDate":"2023-12-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10693702/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138476710","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 and safety of thrombopoietin receptor agonists in solid tumors with chemotherapy-induced thrombocytopenia: a meta-analysis.","authors":"Wen Chen, Yubingxue Liu, Luchun Li, Xianghua Zeng","doi":"10.1186/s40360-023-00707-5","DOIUrl":"10.1186/s40360-023-00707-5","url":null,"abstract":"<p><strong>Objective: </strong>To evaluate the efficacy and safety of thrombopoietin receptor agonists (TPO-RAs) in solid tumors with chemotherapy-induced thrombocytopenia (CIT).</p><p><strong>Methods: </strong>We conducted a comprehensive search of PubMed, FMRS, Cochrane Library, Web of Science, EMBASE, and ClinicalTrials.gov for randomized controlled trials (RCTs) reporting the efficacy and safety of TPO-RAs in solid tumors with CIT. The search was limited to articles published before April 30, 2022. Primary outcomes included chemotherapy dose reduction or delays, platelet transfusion, the incidence of grade 3 or 4 thrombocytopenia, and bleeding events. Secondary outcomes encompassed the incidence of platelet count > 400 × 10⁹/L, adverse events (AEs), serious AEs, thrombosis, and mortality.</p><p><strong>Results: </strong>Our analysis encompassed six studies: five rigorous RCTs and one unique study comparing romiplostim to an observation group, involving a total of 489 patients. For primary outcomes, TPO-RAs significantly reduced the incidence of grade 3 or 4 thrombocytopenia (RR = 0.69, 95% CI: 0.52-0.91). After applying the Bonferroni correction for multiple comparisons, the significance of the reduction in grade 3 or 4 thrombocytopenia incidence persisted (P = 0.008). TPO-RAs showed no significant impact on chemotherapy dose reduction or delays (RR = 0.81, 95% CI: 0.65-1.01), platelet transfusion (RR = 1.04, 95% CI: 0.48-2.27), or bleeding events (RR = 0.50, 95% CI: 0.23-1.10). In terms of safety, there were no significant difference in the incidence of any AEs (RR = 0.98, 95% CI:0.92-1.04), serious AEs (RR = 0.79, 95% CI:0.45-1.40), thrombotic events (RR = 1.20, 95% CI:0.51-2.84) and mortality (RR = 1.15, 95% CI:0.55-2.41).</p><p><strong>Conclusions: </strong>This meta-analysis suggests that TPO-RAs are generally well-tolerated. However, their efficacy in solid tumors with CIT appears limited, as they only demonstrate a reduction in the incidence of grade 3 or 4 thrombocytopenia.</p>","PeriodicalId":9023,"journal":{"name":"BMC Pharmacology & Toxicology","volume":"24 1","pages":"71"},"PeriodicalIF":2.9,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10693054/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138469843","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":"Evaluation of antibody drug delivery efficiency via nebulizer in various airway models and breathing patterns.","authors":"Soon Woo Hong, Kyung Hwa Chang, Chang Jae Woo, Ho Chul Kim, Bong Seop Kwak, Bong Joo Park, Ki Chang Nam","doi":"10.1186/s40360-023-00711-9","DOIUrl":"10.1186/s40360-023-00711-9","url":null,"abstract":"<p><strong>Background: </strong>Nebulizers are commonly used to treat respiratory diseases, which are a major cause of morbidity and mortality. While inhalation therapy with antibodies has been evaluated in preclinical studies and clinical trials for respiratory diseases, it has not yet been approved for treatment. Moreover, there is limited information regarding the delivery efficiency of therapeutic antibodies via nebulizer.</p><p><strong>Methods: </strong>In this study, the nebulization characteristics and drug delivery efficiencies were compared when immunoglobulin G (IgG) was delivered by five nebulizers using two airway models and five breathing patterns. The study confirmed that the delivered dose and drug delivery efficiency were reduced in the child model compared to those in the adult model and in the asthma pattern compared to those in the normal breathing pattern.</p><p><strong>Results: </strong>The NE-SM1 NEPLUS vibrating mesh nebulizer demonstrated the highest delivery efficiency when calculated as a percentage of the loading dose, whereas the PARI BOY SX + LC SPRINT (breath-enhanced) jet nebulizer had the highest delivery efficiency when calculated as a percentage of the emitted dose.</p><p><strong>Conclusion: </strong>The results suggest that the total inspiration volume, output rate, and particle size should be considered when IgG nebulization is used. We, therefore, propose a method for evaluating the efficiency of nebulizer for predicting antibody drug delivery.</p>","PeriodicalId":9023,"journal":{"name":"BMC Pharmacology & Toxicology","volume":"24 1","pages":"70"},"PeriodicalIF":2.9,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10691028/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138469844","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 silico prediction of bioequivalence of atorvastatin tablets based on GastroPlus™ software.","authors":"Lu Wang, Jinliang Chen, Wenjun Chen, Zourong Ruan, Honggang Lou, Dandan Yang, Bo Jiang","doi":"10.1186/s40360-023-00689-4","DOIUrl":"10.1186/s40360-023-00689-4","url":null,"abstract":"<p><p>The prediction of intestinal absorption of various drugs based on computer simulations has been a reality. However, in vivo pharmacokinetic simulations and virtual bioequivalence evaluation based on GastroPlus™ have not been found. This study aimed to simulate plasma concentrations with different dissolution profiles and run population simulations to evaluate the bioequivalence of test and reference products of atorvastation using GastroPlus software. The dissolution profiles of the reference and test products of atorvastatin (20 mg tablets), and clinical plasma concentration-time data of the reference product were used for the simulations. The results showed that the simulated models were successfully established for atorvastatin tablets. Population simulation results indicated that the test formulation was bioequivalent to the reference formulation. The findings suggest that modelling is an essential tool to demonstrating the possibility of pharmacokinetic and bioequivalence for atorvastatin. It will contribute to understanding the potential risks during the development of generic products.</p>","PeriodicalId":9023,"journal":{"name":"BMC Pharmacology & Toxicology","volume":"24 1","pages":"69"},"PeriodicalIF":2.9,"publicationDate":"2023-11-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10685666/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138450846","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":"Determination of biochemical and histopathological changes on testicular and epididymis tissues induced by exposure to insecticide Imidacloprid during postnatal development in rats.","authors":"Amina Sardar, Mehwish David, Sarwat Jahan, Tayyaba Afsar, Aneela Ahmad, Asad Ullah, Ali Almajwal, Huma Shafique, Suhail Razak","doi":"10.1186/s40360-023-00709-3","DOIUrl":"10.1186/s40360-023-00709-3","url":null,"abstract":"<p><strong>Background: </strong>Imidacloprid is a neonicotinoid insecticide belonging to the chloronicotinyl nitroguanidine chemical family. Toxicity of IMD for mammals in scientific studies has shown high mutagenic, immunotoxic, teratogenic and neurotoxic effects. The present study was designed to assess the toxic effects of imidacloprid (IMD) on the testicular and epididymis tissues as well as testosterone levels of neonatal male rats.</p><p><strong>Methods: </strong>Neonatal male rats from postnatal day (PND) 1 to PND 26 were consecutively administered with different concentrations of IMD (1, 5 and 10 mg/kg) subcutaneously. The effect of IMD on body and organ weight, lipid profile, histopathological alterations, oxidative stress and altered testosterone levels were assessed in the testis and plasma.</p><p><strong>Results: </strong>The results of body weight gain showed a significant difference in group 4 (10 mg/kg) animals as compared to the control. A significant increase in total cholesterol and triglycerides, while a decrease in high-density lipoprotein concentrations was evident. Similarly, a significant decrease in concentrations of antioxidant enzymes (CAT and SOD) among all the IMD-treated groups was evident, when compared to the control. Increased production of ROS was also noticed in the highest-dose treatment group. Further, we observed that IMD-treated rats indicated histopathological changes in the testis and epididymis along with a significant decrease in the plasma testosterone concentrations among IMI-treated groups in contrast to the control. Histological examination of the testis of IMD-treated neonatal male rats also showed decreased spermatogenesis in the treated groups when compared to the control. Furthermore, an increase in lumen diameter and a decrease in epithelial height of seminiferous tubules were also observed in IMD-treated rats in comparison with the control.</p><p><strong>Conclusion: </strong>It is concluded that sub-chronic exposure to IMD in neonatal male rats may induce histopathological changes in reproductive tissues and damage normal testicular functions via inducing oxidative stress, decrease in body weight, disturbing normal blood lipid profile and testosterone concentration. IMD exposure can induce pathophysiological effects calls for further evaluation of this widely used insecticide.</p>","PeriodicalId":9023,"journal":{"name":"BMC Pharmacology & Toxicology","volume":"24 1","pages":"68"},"PeriodicalIF":2.9,"publicationDate":"2023-11-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10680247/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138443706","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-silico and in-vitro screening of Asiatic acid and Asiaticoside A against Cathepsin S enzyme.","authors":"Temitope Akinwumi Ajani, Kenechukwu Obikeze, Zandisiwe E Magwebu, Samuel Egieyeh, Chesa G Chauke","doi":"10.1186/s40360-023-00701-x","DOIUrl":"10.1186/s40360-023-00701-x","url":null,"abstract":"<p><strong>Background: </strong>Atherosclerosis is a form of cardiovascular disease that affects the endothelium of the blood vessel. Series of events are involved in the pathophysiology of this disease which includes the breaking down of the connective tissue elastin and collagen responsible for the tensile strength of the arterial wall by proteolytic enzyme. One of these enzymes called Cathepsin S (CatS) is upregulated in the progression of the disease and its inhibition has been proposed to be a promising pharmacological target to improve the prognosis of the disease condition. Asiatic acid and asiaticoside A are both pentacyclic triterpenoids isolated from Centella asiatica. Their use in treating various cardiovascular diseases has been reported.</p><p><strong>Methods: </strong>In this study through in silico and in vitro methods, the pharmacokinetic properties, residue interaction, and inhibitory activities of these compounds were checked against the CatS enzyme. The SwissADME online package and the ToxTree 3.01 version of the offline software were used to determine the physicochemical properties of the compounds.</p><p><strong>Result: </strong>Asiatic acid reported no violation of the Lipinski rule while asiaticoside A violated the rule with regards to its molecular structure and size. The molecular docking was done using Molecular Operating Environment (MOE) and the S-score of - 7.25988, - 7.08466, and - 4.147913 Kcal/mol were recorded for LY300328, asiaticoside A, and asiatic acid respectively. Asiaticoside A has a docking score value (- 7.08466Kcal/mol) close to the co-crystallize compound. Apart from the close docking score, the amino acid residue glycine69 and asparagine163 both interact with the co-crystallized compound and asiaticoside A. The in vitro result clearly shows the inhibitory effect of asiaticoside and asiatic acid. Asiaticoside A has an inhibitory value of about 40% and asiatic acid has an inhibitory value of about 20%.</p><p><strong>Conclusion: </strong>This clearly shows that asiaticoside will be a better drug candidate than asiatic acid in inhibiting the CatS enzyme for the purpose of improving the outcome of atherosclerosis. However, certain modifications need to be made to the structural make-up of asiaticoside A to improve its pharmacokinetics properties.</p>","PeriodicalId":9023,"journal":{"name":"BMC Pharmacology & Toxicology","volume":"24 1","pages":"67"},"PeriodicalIF":2.9,"publicationDate":"2023-11-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10676574/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138440288","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}