Adeoye Bisi O, Oyagbemi Ademola A, Asenuga Ebunoluwa R, Omobowale Temidayo O, Adedapo Adeolu A
Department of Veterinary Pharmacology and Toxicology, University of Ibadan, Ibadan, Nigeria.
Department of Veterinary Physiology and Biochemistry, University of Ibadan, Ibadan, Nigeria.
J Basic Clin Physiol Pharmacol. 2018 Nov 30;30(2):205-217. doi: 10.1515/jbcpp-2017-0120.
Background Cisplatin (CP) is a novel drug of choice in the treatment of cancer but its major limitation is nephrotoxicity, which is dose limiting. Andrographis paniculata (AP) is a common Indian dietary component. It is well known for its medicinal properties. This present study investigated the nephroprotective effect of ethanol leaf extract of Andrographis paniculata (EEAP) on CP-induced nephrotoxicity. Methods CP was used to induce nephrotoxicity in male Wistar rats to study the effect of EEAP on renal damages using hematological parameters, biochemical parameters, histology, and immunohistochemistry studies. Results The effects of EEAP were determined by CP-induced changes in different kidney tissue on antioxidant enzymes, markers of oxidative stress, serum creatinine, and urine parameters. Administration of EEAP (200 mL/kg and 400 mg/kg orally), prior to and following a single dose CP treatment (10 mg/kg i.p), significantly mitigated the CP-induced decrease in antioxidant enzymes, and increase in markers of oxidative stress, serum creatinine, and urinary protein. On histopathological examination of the kidney tissue, there was severe glomerular degeneration and infiltration of inflammatory cells in CP only treated rats, mild glomerular degeneration, and infiltration of inflammatory cells in EEAP pre-treated rats. Furthermore, EEAP activated Nrf2 and mitigated Kim-1 pathways in CP-induced nephrotoxicity. Conclusions The results showed the protective effect of EEAP against CP-induced nephrotoxicity.
顺铂（CP）是治疗癌症的一种新型首选药物，但其主要局限性是肾毒性，这是剂量限制性的。穿心莲是印度一种常见的饮食成分。它以其药用特性而闻名。本研究调查了穿心莲乙醇叶提取物（EEAP）对顺铂诱导的肾毒性的肾保护作用。方法：使用顺铂诱导雄性Wistar大鼠肾毒性，通过血液学参数、生化参数、组织学和免疫组织化学研究来研究EEAP对肾脏损伤的影响。结果：通过顺铂诱导的不同肾组织对抗氧化酶、氧化应激标志物、血清肌酐和尿液参数的变化来确定EEAP的作用。在单次剂量顺铂治疗（10mg/kg腹腔注射）之前和之后口服EEAP（200mg/kg和400mg/kg），显著减轻了顺铂诱导的抗氧化酶降低以及氧化应激标志物、血清肌酐和尿蛋白的增加。对肾脏组织进行组织病理学检查，仅接受顺铂治疗的大鼠出现严重的肾小球变性和炎性细胞浸润，而EEAP预处理的大鼠出现轻度肾小球变性和炎性细胞浸润。此外，EEAP在顺铂诱导的肾毒性中激活了Nrf2并减轻了Kim-1通路。结论：结果表明EEAP对顺铂诱导的肾毒性具有保护作用。
