Department of Biochemistry, Faculty of Medicine, Suleyman Demirel University, 32000, Isparta, Turkey.
Department of Pharmacology, Faculty of Medicine, Suleyman Demirel University, Isparta, Turkey.
Mol Biol Rep. 2022 Jul;49(7):6125-6133. doi: 10.1007/s11033-022-07403-3. Epub 2022 Apr 2.
Cisplatin (CPN) is used in the treatment of various cancers. However, the especially nephrotoxic effect is limiting its use. We aimed to evaluate the renoprotective effects of Irbesartan (IBN) on CPN-induced acute kidney injury via mitochondrial stress related apoptosis.
32 rats were divided into 4 groups as control, CPN, CPN + IBN and IBN. Water or IBN 50 mg/kg (orally) was administered for 7 days and a single dose of CPN (5 mg/kg) intraperitoneally was given CPN and CPN + IBN groups on fourth day of experiment. At the end of the experiment, serum BUN and creatinine (Cre) levels, which are the indicators of kidney function are measured. Bcl-2-associated X protein (Bax) and B-cell-lymphoma-2 (Bcl-2) mRNA levels were analyzed by using qRT-PCR from kidneys as a mitochondrial stress indicator. Also, active caspase-3(cas-3) protein and tumor necrosis factor alpha (TNF-α) expressions were examined by immunostaining of the kidney tissues. For evaluation of oxidative stress, malondialdehyde (MDA), total oxidant status (TOS) and total antioxidant status (TAS) levels of renal tissues were measured and oxidative stress index (OSI) were calculated. CPN increased serum BUN and creatinine levels. Also, MDA, TOS and OSI levels were significantly elevated and TAS levels decreased in the CPN group. Moreover, CPN elevated the levels of Bax, active cas-3 protein and TNF-α expressions and suppressed Bcl-2 levels. IBN treatment reversed all these changes.
IBN significantly regressed kidney damage by its anti-inflammatory and antioxidant activity via inhibiting mitochondrial stress. IBN could be used as a renoprotective agent in CPN-induced kidney injury.
顺铂（CPN）用于治疗各种癌症。然而，其特别的肾毒性作用限制了它的使用。我们旨在通过与线粒体应激相关的凋亡来评估厄贝沙坦（IBN）对 CPN 诱导的急性肾损伤的肾保护作用。
32 只大鼠分为 4 组，分别为对照组、CPN 组、CPN+IBN 组和 IBN 组。第 4 天实验时，CPN 组和 CPN+IBN 组腹腔内给予单剂量 5mg/kg 的 CPN，同时 CPN+IBN 组给予 50mg/kg 的 IBN 灌胃，连续 7 天。实验结束时，检测血清 BUN 和肌酐（Cre）水平，这是肾功能的指标。通过 qRT-PCR 从肾脏中分析 Bcl-2 相关 X 蛋白（Bax）和 B 细胞淋巴瘤-2（Bcl-2）mRNA 水平，作为线粒体应激的指标。此外，通过免疫组织化学染色检测肾组织中活性半胱天冬酶-3（cas-3）蛋白和肿瘤坏死因子-α（TNF-α）的表达。为了评估氧化应激，测量肾组织中丙二醛（MDA）、总氧化剂状态（TOS）和总抗氧化状态（TAS）的水平，并计算氧化应激指数（OSI）。CPN 增加了血清 BUN 和肌酐水平。此外，CPN 组 MDA、TOS 和 OSI 水平显著升高，TAS 水平降低。此外，CPN 增加了 Bax、活性 cas-3 蛋白和 TNF-α的表达水平，并抑制了 Bcl-2 水平。IBN 治疗逆转了所有这些变化。
IBN 通过抑制线粒体应激，显著减轻炎症和氧化应激，从而减轻肾损伤。IBN 可作为 CPN 诱导的肾损伤的肾保护剂。
