The most prominent adverse effects of nonsteroidal anti-inflammatory drugs (NSAIDs) such as diclofenac (DF) are hepato-renal damage. Natural antioxidants can be preferred as an alternative and/or combination to improve this damage. This present study was conducted to evaluate the protective effect of Tubuloside A (TA) against diclofenac (DF)-induced hepato-renal damage. TA (1 mg/kg, ip) was administered to male Sprague–Dawley rats for 5 days, and DF (50 mg/kg, ip) was administered on Days 4 and 5. Plasma aspartate amino transferase, alanine amino transferase, alkaline phosphatase, blood urea nitrogen and creatinine were measured to evaluate liver and kidney functions. Additionally, oxidative stress parameters (malondialdehyde, glutathione, superoxide dismutase, catalase, and 8-oxo-7,8-dihydro-2′-deoxyguanosine) in blood, liver, and kidney tissues, changes in mRNA expression of genes involved in the Nrf2/HO-1 signalling pathway (Nrf2, HO-1, NQO-1, IL-6, iNOS, Cox-2, TNF-α, IL1-β and NFκB) and apoptotic process (Bcl-2, Cas-3 and Bax) in liver and kidney tissues were determined. Additionally, tissue sections were evaluated histopathologically. Biochemical, histopathological, and molecular results demonstrated the hepato-renal toxic effects of DF, and TA treatment protected the liver and kidney from DF-induced damage. This provides an explanation for the hepato-nephro damage caused by DF and offers new ideas and drug targets together with TA for the prevention and treatment of DF injury.

中文翻译：

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Tubuloside A 是一种苯乙醇苷，通过 Nrf2/HO-1 减轻双氯芬酸诱导的肝肾氧化损伤

双氯芬酸 (DF) 等非甾体抗炎药 (NSAID) 最显着的不良反应是肝肾损伤。天然抗氧化剂可以优选作为替代品和/或组合来改善这种损害。本研究旨在评估管苷 A (TA) 对双氯芬酸 (DF) 诱导的肝肾损伤的保护作用。对雄性 Sprague-Dawley 大鼠给予 TA（1 mg/kg，腹腔注射）5 天，并在第 4 天和第 5 天给予 DF（50 mg/kg，腹腔注射）。 血浆天冬氨酸氨基转移酶、丙氨酸氨基转移酶、碱性磷酸酶、血尿素氮、肌酐测定，评价肝、肾功能。此外，血液、肝脏和肾脏组织中的氧化应激参数（丙二醛、谷胱甘肽、超氧化物歧化酶、过氧化氢酶和8-氧代-7,8-二氢-2'-脱氧鸟苷）、Nrf2相关基因的mRNA表达变化/ HO - 1信号通路 ( Nrf2 , HO - 1 , NQO - 1 , IL - 6 , iNOS , Cox - 2 , TNF - α , IL1 - β和NFκB ) 和凋亡过程 ( Bcl - 2 , Cas - 3和Bax )）在肝和肾组织中进行了测定。此外，对组织切片进行组织病理学评估。生化、组织病理学和分子结果证明了 DF 的肝肾毒性作用，TA 治疗可以保护肝脏和肾脏免受 DF 引起的损伤。这为DF引起的肝肾损伤提供了解释，并与TA一起为DF损伤的防治提供了新的思路和药物靶点。