{"title":"橙皮苷、抗坏血酸及其联合应用对抗结核药物肝毒性大鼠氧化应激、血脂异常及组织学改变的保护作用。","authors":"Nathiya Shanmugam, Preethi Umanath, Vennila Gurusamy","doi":"10.4103/ijp.ijp_116_24","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Hesperidin and ascorbic acid (AA) enhance cellular antioxidant defense systems by neutralizing the free radicals which formed during oxidative stress that could offer protective effects against drug-induced liver injury. Hence, this study aims to investigate the effect of hesperidin, AA and their combination against antitubercular drug (ATDs)- induced hepatotoxicity in Wistar albino rats.</p><p><strong>Materials and methods: </strong>The rats were divided into six groups of 6 animals each. Isoniazid (H), Rifampicin (R), and pyrazinamide (Z) (27, 54, 135 mg/kg.b.wt) were co-administration for 50 days to induce hepatotoxicity. Hesperidin 200 mg/kg and AA 100 mg/kg p.o were administered 1 h before ATDs administration. At the end of the study, blood and liver tissues were collected and subjected to biochemical and histopathological examination. Biochemical parameters, serum marker enzymes (aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, acid phosphatase, Gamma glutamyltransferase, and lactate dehydrogenase), lipid peroxidation (LPO), antioxidant enzymes (superoxide dismutase, catalase, GSH, glutathione peroxidase, GR, Vitamin C, and Vitamin E), lipid profile, membrane bound ATPase, and histological changes of liver were assessed.</p><p><strong>Results: </strong>Our results revealed that HRZ-induced hepatotoxicity was evident by significant (P < 0.001) elevation in level of urea, creatinine, bilirubin, liver marker enzymes, lipid profile (P < 0.01), and LPO (P < 0.001) along with significant decline in the level of total protein, albumin (P > 0.05), ATPase (P < 0.001), and antioxidant enzymes (P < 0.001). Treatment with HDN and AA significantly reduced the changes induced by HRZ. However, compared to individual treatment, combined treatment with HDN and AA significantly (P < 0.001) ameliorated all the changes induced by ATDs and improved the hepatic architecture to near normal.</p><p><strong>Conclusion: </strong>The combination of HDN and AA demonstrated a synergistic therapeutic effect against HRZ-induced liver injury; hence, this combination represents a potential novel strategy for the management of anti-TB drug-induced liver damage.</p>","PeriodicalId":13490,"journal":{"name":"Indian Journal of Pharmacology","volume":"57 1","pages":"4-11"},"PeriodicalIF":1.4000,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Protective effect of hesperidin, ascorbic acid and their combination on oxidative stress, dyslipidemia, and histological changes in antitubercular drug-induced hepatotoxicity in rats.\",\"authors\":\"Nathiya Shanmugam, Preethi Umanath, Vennila Gurusamy\",\"doi\":\"10.4103/ijp.ijp_116_24\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>Hesperidin and ascorbic acid (AA) enhance cellular antioxidant defense systems by neutralizing the free radicals which formed during oxidative stress that could offer protective effects against drug-induced liver injury. Hence, this study aims to investigate the effect of hesperidin, AA and their combination against antitubercular drug (ATDs)- induced hepatotoxicity in Wistar albino rats.</p><p><strong>Materials and methods: </strong>The rats were divided into six groups of 6 animals each. Isoniazid (H), Rifampicin (R), and pyrazinamide (Z) (27, 54, 135 mg/kg.b.wt) were co-administration for 50 days to induce hepatotoxicity. Hesperidin 200 mg/kg and AA 100 mg/kg p.o were administered 1 h before ATDs administration. At the end of the study, blood and liver tissues were collected and subjected to biochemical and histopathological examination. Biochemical parameters, serum marker enzymes (aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, acid phosphatase, Gamma glutamyltransferase, and lactate dehydrogenase), lipid peroxidation (LPO), antioxidant enzymes (superoxide dismutase, catalase, GSH, glutathione peroxidase, GR, Vitamin C, and Vitamin E), lipid profile, membrane bound ATPase, and histological changes of liver were assessed.</p><p><strong>Results: </strong>Our results revealed that HRZ-induced hepatotoxicity was evident by significant (P < 0.001) elevation in level of urea, creatinine, bilirubin, liver marker enzymes, lipid profile (P < 0.01), and LPO (P < 0.001) along with significant decline in the level of total protein, albumin (P > 0.05), ATPase (P < 0.001), and antioxidant enzymes (P < 0.001). Treatment with HDN and AA significantly reduced the changes induced by HRZ. However, compared to individual treatment, combined treatment with HDN and AA significantly (P < 0.001) ameliorated all the changes induced by ATDs and improved the hepatic architecture to near normal.</p><p><strong>Conclusion: </strong>The combination of HDN and AA demonstrated a synergistic therapeutic effect against HRZ-induced liver injury; hence, this combination represents a potential novel strategy for the management of anti-TB drug-induced liver damage.</p>\",\"PeriodicalId\":13490,\"journal\":{\"name\":\"Indian Journal of Pharmacology\",\"volume\":\"57 1\",\"pages\":\"4-11\"},\"PeriodicalIF\":1.4000,\"publicationDate\":\"2025-01-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Indian Journal of Pharmacology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.4103/ijp.ijp_116_24\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2025/5/6 0:00:00\",\"PubModel\":\"Epub\",\"JCR\":\"Q4\",\"JCRName\":\"PHARMACOLOGY & PHARMACY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Indian Journal of Pharmacology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.4103/ijp.ijp_116_24","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/5/6 0:00:00","PubModel":"Epub","JCR":"Q4","JCRName":"PHARMACOLOGY & PHARMACY","Score":null,"Total":0}
Protective effect of hesperidin, ascorbic acid and their combination on oxidative stress, dyslipidemia, and histological changes in antitubercular drug-induced hepatotoxicity in rats.
Background: Hesperidin and ascorbic acid (AA) enhance cellular antioxidant defense systems by neutralizing the free radicals which formed during oxidative stress that could offer protective effects against drug-induced liver injury. Hence, this study aims to investigate the effect of hesperidin, AA and their combination against antitubercular drug (ATDs)- induced hepatotoxicity in Wistar albino rats.
Materials and methods: The rats were divided into six groups of 6 animals each. Isoniazid (H), Rifampicin (R), and pyrazinamide (Z) (27, 54, 135 mg/kg.b.wt) were co-administration for 50 days to induce hepatotoxicity. Hesperidin 200 mg/kg and AA 100 mg/kg p.o were administered 1 h before ATDs administration. At the end of the study, blood and liver tissues were collected and subjected to biochemical and histopathological examination. Biochemical parameters, serum marker enzymes (aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, acid phosphatase, Gamma glutamyltransferase, and lactate dehydrogenase), lipid peroxidation (LPO), antioxidant enzymes (superoxide dismutase, catalase, GSH, glutathione peroxidase, GR, Vitamin C, and Vitamin E), lipid profile, membrane bound ATPase, and histological changes of liver were assessed.
Results: Our results revealed that HRZ-induced hepatotoxicity was evident by significant (P < 0.001) elevation in level of urea, creatinine, bilirubin, liver marker enzymes, lipid profile (P < 0.01), and LPO (P < 0.001) along with significant decline in the level of total protein, albumin (P > 0.05), ATPase (P < 0.001), and antioxidant enzymes (P < 0.001). Treatment with HDN and AA significantly reduced the changes induced by HRZ. However, compared to individual treatment, combined treatment with HDN and AA significantly (P < 0.001) ameliorated all the changes induced by ATDs and improved the hepatic architecture to near normal.
Conclusion: The combination of HDN and AA demonstrated a synergistic therapeutic effect against HRZ-induced liver injury; hence, this combination represents a potential novel strategy for the management of anti-TB drug-induced liver damage.
期刊介绍:
Indian Journal of Pharmacology accepts, in English, review articles, articles for educational forum, original research articles (full length and short communications), letter to editor, case reports and interesting fillers. Articles concerning all aspects of pharmacology will be considered. Articles of general interest (e.g. methods, therapeutics, medical education, interesting websites, new drug information and commentary on a recent topic) are also welcome.