Abstract

Drug-induced liver injury is a common cause of acute liver failure. Dapsone is increasingly used in combination with rifampicin for the treatment of leprosy and also for several dermatological disorders. Clinically, abnormal liver function and focal bile duct destruction were reported after dapsone therapy. Lagerstroemia speciosa Pers., commonly known as Banaba has been traditionally used to treat various ailments including diabetes and obesity due to its antioxidant and anti-inflammatory efficacies. This study investigated the hepatoprotective effect of ethanolic banaba leaves extract (EBLE) against dapsone-induced hepatotoxicity in rats. Dapsone (30 mg/kg, i.p.) was administered twice daily for 30 days. In separate groups, rats were post-treated orally with EBLE (250 and 500 mg/kg) and silymarin (100 mg/kg) once daily for 30 days after dapsone administration. The marker enzymes of hepatotoxicity, oxidative stress markers, inflammatory markers and histopathology of liver were done. HPTLC analysis confirmed the presence of 12.87 µg of corosolic acid per mg of EBLE. Dapsone administration-induced significant (p < 0.001) elevation of marker enzymes of hepatotoxicity in serum. This treatment also increased lipid peroxidation (p < 0.001) and pro-inflammatory markers (tumor necrosis factor-alpha, transforming growth factor-beta, and nuclear factor kappa-B) expressions (p < 0.001) and decreased antioxidants (p < 0.001) such superoxide dismutase, catalase and glutathione in the liver tissue. All these abnormalities were significantly (p < 0.001) mitigated after EBLE (500 mg/kg) and silymarin post-treatments. The results of this study suggest that silymarin and EBLE can be used for dapsone-induced hepatotoxicity.

摘要

药物性肝损伤是急性肝功能衰竭的常见原因。氨苯砜越来越多地与利福平联合用于治疗麻风病和几种皮肤病。临床上报告氨苯砜治疗后肝功能异常和局灶性胆管破坏。紫薇Pers.，通常被称为 Banaba，由于其抗氧化和抗炎功效，传统上被用于治疗各种疾病，包括糖尿病和肥胖症。本研究调查了乙醇香蕉叶提取物 (EBLE) 对氨苯砜诱导的大鼠肝毒性的保肝作用。氨苯砜 (30 mg/kg, ip) 每天两次给药，持续 30 天。在不同的组中，大鼠在氨苯砜给药后每天一次口服 EBLE（250 和 500 mg/kg）和水飞蓟素（100 mg/kg），持续 30 天。进行肝毒性标志酶、氧化应激标志物、炎症标志物及肝脏组织病理学检查。HPTLC 分析证实每毫克 EBLE 含有 12.87 微克科罗索酸。氨苯砜给药诱导显着（p < 0.001) 血清中肝毒性标志酶的升高。这种治疗还增加了脂质过氧化（p  < 0.001）和促炎标志物（肿瘤坏死因子-α、转化生长因子-β和核因子 kappa-B）的表达（p  < 0.001）并减少了抗氧化剂（p  < 0.001）如肝组织中的超氧化物歧化酶、过氧化氢酶和谷胱甘肽。 在 EBLE (500 mg/kg) 和水飞蓟素后处理后，所有这些异常情况均显着减轻 ( p < 0.001)。本研究结果表明，水飞蓟素和 EBLE 可用于氨苯砜诱导的肝毒性。