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水合桑色素对白化Wistar大鼠利福平诱导的肝毒性和肾毒性的治疗潜力:对器官功能、氧化应激和炎症反应的调节

Therapeutic Potential of Morin Hydrate Against Rifampicin Induced Hepato and Renotoxicity in Albino Wistar Rats: Modulation of Organ Function, Oxidative Stress and Inflammatory Response.

作者信息

Rana Harvesh Kumar, Singh Amit Kumar, Pandey Abhay Kumar

机构信息

Department of Biochemistry, University of Allahabad, Prayagraj (Allahabad), 211002 India.

Present Address: Department of Zoology, Feroze Gandhi College, Raebareli, 229001 India.

出版信息

Indian J Clin Biochem. 2024 Apr;39(2):197-206. doi: 10.1007/s12291-023-01145-0. Epub 2023 Aug 4.

Abstract

Tuberculosis (TB) is a challenging public health issue, particularly in poor and developing countries. Rifampicin (RIF) is one of the most common first-line anti-TB drugs but it is known for its adverse effects on the hepato-renal system. The present study investigated the efficacy of morin hydrate (MH) in protecting hepato-renal damage inflicted by RIF in rats. RIF (50 mg/kg), and a combination of RIF (50 mg/kg) and MH (50 mg/kg) were administered orally for 4 weeks in rats. Silymarin (50 mg/kg) was used as a positive control. Increased levels of serological parameters such as AST, ALT, ALP, LDH, GGT, bilirubin, triglyceride, total cholesterol, urea, uric acid, creatinine, TNF-α, IFN-γ, IL-6 along with the decreased level of IL-10, total protein and albumin were used as markers of hepatic and renal injury. Oxidative damage in the tissues was measured by the increase in lipid peroxidation and decline in GSH, SOD and catalase activities. Histopathology of liver slices was used to study hepatic architecture. Four-week RIF treatment produced altered serological parameters with an increase in pro-inflammatory cytokines in serum suggesting hepatotoxicity and nephrotoxicity. The antioxidant status of the liver and kidney (increased lipid peroxidation and decline in GSH, SOD and catalase) was compromised. Cellular damage and necrosis were observed in liver slices. MH supplementation with RIF improved hepato-renal functions by restoring the serum and tissue markers towards normal values. Histological observations authenticated the results. MH supplementation also reduced the production of pro-inflammatory cytokines. Thus, the results revealed that MH provides protection against RIF-induced hepato-renal injury.

摘要

结核病(TB)是一个具有挑战性的公共卫生问题,在贫穷和发展中国家尤为如此。利福平(RIF)是最常用的一线抗结核药物之一,但它以对肝-肾系统有不良反应而闻名。本研究调查了水合桑色素(MH)对利福平所致大鼠肝-肾损伤的保护作用。将利福平(50毫克/千克)以及利福平(50毫克/千克)与水合桑色素(50毫克/千克)的组合经口给予大鼠4周。水飞蓟宾(50毫克/千克)用作阳性对照。血清学参数如天冬氨酸转氨酶(AST)、丙氨酸转氨酶(ALT)、碱性磷酸酶(ALP)、乳酸脱氢酶(LDH)、γ-谷氨酰转移酶(GGT)、胆红素、甘油三酯、总胆固醇、尿素、尿酸、肌酐、肿瘤坏死因子-α(TNF-α)、干扰素-γ(IFN-γ)、白细胞介素-6(IL-6)水平升高,同时白细胞介素-10(IL-10)、总蛋白和白蛋白水平降低,被用作肝和肾损伤的标志物。通过脂质过氧化增加以及谷胱甘肽(GSH)、超氧化物歧化酶(SOD)和过氧化氢酶活性下降来测量组织中的氧化损伤。肝脏切片的组织病理学用于研究肝脏结构。四周的利福平治疗导致血清学参数改变,血清中促炎细胞因子增加,提示肝毒性和肾毒性。肝脏和肾脏的抗氧化状态(脂质过氧化增加以及GSH、SOD和过氧化氢酶下降)受到损害。在肝脏切片中观察到细胞损伤和坏死。利福平与水合桑色素联合使用通过使血清和组织标志物恢复到正常值而改善了肝肾功能。组织学观察证实了该结果。补充水合桑色素还减少了促炎细胞因子的产生。因此,结果表明水合桑色素对利福平诱导的肝-肾损伤具有保护作用。

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