{"title":"<i>In Vivo</i> and <i>In Silico</i> Pharmacokinetics Studies on Coumarinolignoid Cliv-92: Unraveling its Effect on Rifampicin-Induced Hepatic Damage.","authors":"Ajay Kumar, Sarfaraz Alam, Sudeep Tandon, Karuna Shanker, Feroz Khan, Dharmendra Saikia","doi":"10.2174/0115680266329609241223114551","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Drug-induced hepatotoxicity is a major concern and is caused by all classes of medications, indicating a key area of research. Antitubercular drugs have a beneficial effect but cause hepatotoxicity on prolonged use.</p><p><strong>Aim: </strong>The present work aimed to investigate the role of rifampicin-induced hepatic damage and the effect of Cliv-92 on rifampicin-induced alteration in rats.</p><p><strong>Methods: </strong>Rats were administered with rifampicin, Cliv-92, and silymarin (standard) orally in 0.5% carboxymethyl cellulose (CMC) suspension, in doses of 100 mg/kg, once daily for fourteen days, one hour before the administration of rifampicin. Control animals were treated with 0.5% CMC. On the 14<sup>th</sup> day, 1hr after the last drug administration, tissue was collected, homogenized, and various parameters, viz. SOD, CAT, GPX, and cytochromes, were estimated from rat liver supernatant and compared with the control group. Blood serum parameters were also measured. Simultaneously, antioxidant activity and <i>in silico </i>studies were performed. The constituent isoforms of Cliv-92 and silymarin and their metabolites were analyzed for different pharmacokinetic characteristics. Silymarin was used as a standard drug.</p><p><strong>Results: </strong>The result of the study suggests that the hepatoprotective potential of Cliv-92 is due to its antioxidant property and inhibitory effect on hepatoproteins, cytochromes (CPY450). An <i>in-silico</i> finding validates the safety profile of Cliv-92, its metabolites, and the standard drug silymarin and also explains that the drug is non-mutagenic.</p><p><strong>Conclusion: </strong>The result of this study indicated that both Cliv-92 and silymarin could be used to avoid drug-induced overload and hepatic damage.</p>","PeriodicalId":11076,"journal":{"name":"Current topics in medicinal chemistry","volume":" ","pages":"1016-1031"},"PeriodicalIF":3.3000,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Current topics in medicinal chemistry","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.2174/0115680266329609241223114551","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"CHEMISTRY, MEDICINAL","Score":null,"Total":0}
引用次数: 0
Abstract
Background: Drug-induced hepatotoxicity is a major concern and is caused by all classes of medications, indicating a key area of research. Antitubercular drugs have a beneficial effect but cause hepatotoxicity on prolonged use.
Aim: The present work aimed to investigate the role of rifampicin-induced hepatic damage and the effect of Cliv-92 on rifampicin-induced alteration in rats.
Methods: Rats were administered with rifampicin, Cliv-92, and silymarin (standard) orally in 0.5% carboxymethyl cellulose (CMC) suspension, in doses of 100 mg/kg, once daily for fourteen days, one hour before the administration of rifampicin. Control animals were treated with 0.5% CMC. On the 14th day, 1hr after the last drug administration, tissue was collected, homogenized, and various parameters, viz. SOD, CAT, GPX, and cytochromes, were estimated from rat liver supernatant and compared with the control group. Blood serum parameters were also measured. Simultaneously, antioxidant activity and in silico studies were performed. The constituent isoforms of Cliv-92 and silymarin and their metabolites were analyzed for different pharmacokinetic characteristics. Silymarin was used as a standard drug.
Results: The result of the study suggests that the hepatoprotective potential of Cliv-92 is due to its antioxidant property and inhibitory effect on hepatoproteins, cytochromes (CPY450). An in-silico finding validates the safety profile of Cliv-92, its metabolites, and the standard drug silymarin and also explains that the drug is non-mutagenic.
Conclusion: The result of this study indicated that both Cliv-92 and silymarin could be used to avoid drug-induced overload and hepatic damage.
期刊介绍：
Current Topics in Medicinal Chemistry is a forum for the review of areas of keen and topical interest to medicinal chemists and others in the allied disciplines. Each issue is solely devoted to a specific topic, containing six to nine reviews, which provide the reader a comprehensive survey of that area. A Guest Editor who is an expert in the topic under review, will assemble each issue. The scope of Current Topics in Medicinal Chemistry will cover all areas of medicinal chemistry, including current developments in rational drug design, synthetic chemistry, bioorganic chemistry, high-throughput screening, combinatorial chemistry, compound diversity measurements, drug absorption, drug distribution, metabolism, new and emerging drug targets, natural products, pharmacogenomics, and structure-activity relationships. Medicinal chemistry is a rapidly maturing discipline. The study of how structure and function are related is absolutely essential to understanding the molecular basis of life. Current Topics in Medicinal Chemistry aims to contribute to the growth of scientific knowledge and insight, and facilitate the discovery and development of new therapeutic agents to treat debilitating human disorders. The journal is essential for every medicinal chemist who wishes to be kept informed and up-to-date with the latest and most important advances.
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