The ethanol leaf extract of Andrographis paniculata blunts acute renal failure in cisplatin-induced injury in rats through inhibition of Kim-1 and upregulation of Nrf2 pathway
The ethanol leaf extract of Andrographis paniculata blunts acute renal failure in cisplatin-induced injury in rats through inhibition of Kim-1 and upregulation of Nrf2 pathway
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DOI：
10.1515/jbcpp-2017-0120
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发表时间：
2019-03-01
影响因子：
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通讯作者：
Adedapo, Adeolu A.
中科院分区：
文献类型：
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作者：
Adeoye, Bisi O.;Oyagbemi, Ademola A.;Adedapo, Adeolu A.
背景：顺铂（CP）是一种新型的肿瘤治疗药物，但其主要局限性是肾毒性，这是一个剂量限制。穿心莲（AP）是印度常见的膳食成分。它以其药用特性而闻名。本研究旨在探讨穿心莲叶乙醇提取物（EEAP）对CP所致肾毒性的保护作用。方法：采用CP致雄性Wistar大鼠肾毒性，通过血液学、生化、组织学和免疫组化等指标，观察EEAP对CP所致肾损伤的保护作用。EEAP的影响通过CP诱导的不同肾脏组织中抗氧化酶、氧化应激标志物、血清肌酐和尿液参数的变化来确定。在单剂量CP治疗（10 mg/kg i.p）之前和之后给予EEAP（200 mL/kg和400 mg/kg口服），显著减轻了CP诱导的抗氧化酶减少，以及氧化应激标志物、血清肌酐和尿蛋白增加。在肾组织的组织病理学检查中，仅CP处理的大鼠中存在严重的肾小球变性和炎性细胞浸润，EEAP预处理的大鼠中存在轻度的肾小球变性和炎性细胞浸润。结论：EEAP对CP肾毒性具有保护作用。
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.