Wogonin pre-treatment attenuates cisplatin-induced nephrotoxicity in rats: Impact on PPAR-γ, inflammation, apoptosis and Wnt/β-catenin pathway
Wogonin pre-treatment attenuates cisplatin-induced nephrotoxicity in rats: Impact on PPAR-γ, inflammation, apoptosis and Wnt/β-catenin pathway
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DOI：
10.1016/j.cbi.2019.05.029
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发表时间：
2019-08-01
影响因子：
5.1
通讯作者：
Fawzy, Hala M.
中科院分区：
文献类型：
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作者：
Badawy, Alaa M.;El-Naga, Reem N.;Fawzy, Hala M.
顺铂是一种铂类化疗药物，用于多种恶性肿瘤;然而，顺铂治疗后过度的肾毒性是剂量限制性破坏性反应。本研究旨在探讨汉黄芩素（一种强有力的抗氧化、抗炎和抗肿瘤药物）在顺铂诱导的大鼠肾损伤模型中可能的肾保护作用。另外还研究了潜在的肾保护机制。汉黄芩素以40 mg/kg剂量给药。注射顺铂的大鼠中BUN和血清肌酐水平显著升高表明急性肾毒性。此外，顺铂增强脂质过氧化，减少GSH，过氧化氢酶和PPAR-gamma水平。此外，注射顺铂的大鼠显示IL-β、TNF-α、NF-κ B和caspase-3酶活性的组织水平显著升高。值得注意的是，汉黄芩素预处理改善了顺铂诱导的肾毒性指数、氧化应激、炎症和细胞凋亡。此外，汉黄芩素上调PPAR-gamma表达。Wnt/beta-catenin通路的参与是有争议的;然而，我们的研究结果表明，顺铂显著诱导了Wnt/beta-catenin通路。汉黄芩素预处理显著减弱Wnt/β-连环蛋白途径。总的来说，这些发现表明汉黄芩素是一种有前途的肾保护剂，通过减少氧化应激、炎症以及诱导PPAR-gamma来提高顺铂的治疗指数。此外，Wnt/β-catenin通路部分参与顺铂肾毒性的发病机制。
Cisplatin, a platinum chemotherapeutic agent, is used in a diversity of malignancies; nevertheless, the excessive nephrotoxicity following cisplatin treatment is the dose-limiting devastating reaction. This study was designed to explore the possible nephroprotective impact of wogonin, a forceful anti-oxidant, anti-inflammatory, and anti-tumor agent, in a rat model of cisplatin-induced renal injury. The potential nephroprotective mechanisms were additionally investigated. Wogonin was given at a dose of 40 mg/kg. Acute nephrotoxicity was indicated by a significant rise in BUN, and serum creatinine levels in cisplatin-injected rats. Also, cisplatin enhanced the lipid peroxidation, diminished GSH, catalase, and PPAR-gamma levels. Additionally, cisplatin-injected rats showed a significant rise in tissue levels of IL-beta, TNF-alpha, NF-kappa B, and caspase-3 enzymatic activity. Notably, the pre-treatment with wogonin ameliorated the nephrotoxicity indices, oxidative stress, inflammation, and apoptosis induced by cisplatin. Also, wogonin up-regulated PPAR-gamma expression. The involvement of Wnt/beta-catenin pathway was debatable; however, our findings showed that it was significantly induced by cisplatin. Wogonin pre-treatment markedly attenuated Wnt/beta-catenin pathway. Collectively, these findings imply that wogonin is a promising nephroprotective agent that improves the therapeutic index of cisplatin via reducing oxidative stress, inflammation as well as inducing PPAR-gamma. Also, Wnt/beta-catenin pathway is partially involved in the pathogenesis of cisplatin nephrotoxicity.