Shanmugam Nathiya, Umanath Preethi, Gurusamy Vennila
Department of Pharmacology, KMCH Institute of Health Sciences and Research, Coimbatore, Tamil Nadu, India.
Department of Anatomy, KMCH Institute of Health Sciences and Research, Coimbatore, Tamil Nadu, India.
Indian J Pharmacol. 2025 Jan 1;57(1):4-11. doi: 10.4103/ijp.ijp_116_24. Epub 2025 May 6.
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.
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.
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.
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.
橙皮苷和抗坏血酸（AA）通过中和氧化应激过程中形成的自由基来增强细胞抗氧化防御系统，这可能对药物性肝损伤提供保护作用。因此，本研究旨在探讨橙皮苷、AA及其组合对Wistar白化大鼠抗结核药物（ATD）诱导的肝毒性的影响。
将大鼠分为六组，每组6只动物。异烟肼（H）、利福平（R）和吡嗪酰胺（Z）（27、54、135mg/kg体重）联合给药50天以诱导肝毒性。在给予ATD前1小时口服200mg/kg橙皮苷和100mg/kg AA。在研究结束时，收集血液和肝脏组织并进行生化和组织病理学检查。评估生化参数、血清标志物酶（天冬氨酸转氨酶、丙氨酸转氨酶、碱性磷酸酶、酸性磷酸酶、γ-谷氨酰转移酶和乳酸脱氢酶）、脂质过氧化（LPO）、抗氧化酶（超氧化物歧化酶、过氧化氢酶、谷胱甘肽、谷胱甘肽过氧化物酶、GR、维生素C和维生素E）、血脂谱、膜结合ATP酶以及肝脏的组织学变化。
我们的结果显示，HRZ诱导的肝毒性表现为尿素、肌酐、胆红素、肝脏标志物酶、血脂谱（P<0.01）和LPO（P<0.001）水平显著升高（P<0.001），同时总蛋白、白蛋白（P>0.05）、ATP酶（P<0.001）和抗氧化酶（P<0.001）水平显著下降。用HDN和AA治疗显著降低了HRZ诱导的变化。然而，与单独治疗相比，HDN和AA联合治疗显著（P<0.001）改善了ATD诱导的所有变化，并使肝脏结构恢复到接近正常。
HDN和AA的组合对HRZ诱导的肝损伤具有协同治疗作用；因此，这种组合代表了一种潜在的新型策略，用于管理抗结核药物引起的肝损伤。
