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木犀草素通过抗氧化、抗炎、抗凋亡和 Nrf2/HO-1 信号通路保护醋酸铅诱导的肾毒性。

Luteolin protects against lead acetate-induced nephrotoxicity through antioxidant, anti-inflammatory, anti-apoptotic, and Nrf2/HO-1 signaling pathways.

机构信息

Surgery Department, College of Medicine, Al-Qunfudah Branch, Umm Al-Qura University, Makkah, Saudi Arabia.

Biotechnology Department, College of Science, Taif University, Taif, Saudi Arabia.

出版信息

Mol Biol Rep. 2020 Apr;47(4):2591-2603. doi: 10.1007/s11033-020-05346-1. Epub 2020 Mar 7.

DOI:10.1007/s11033-020-05346-1
PMID:32144527
Abstract

Lead (Pb) is one of the most common heavy metal pollutants affecting living organisms. It induces nephrotoxicity with significant alterations in renal structure and function. Luteolin (LUT) a flavonoid present in various plant products is well known for exhibiting numerous pharmacological properties. We evaluated the protective efficacy of LUT against Pb-induced renal injury in male Wistar rats. Four experimental groups: control, LUT (50 mg/kg, orally), PbAc (20 mg/kg, i.p.), LUT + PbAc (at the aforementioned doses) were maintained for 7 days. PbAc administration significantly increased renal Pb accumulation, urea, and creatinine levels in serum, and induced renal histological alterations. Additionally, compared to the control rats, PbAc-treated rats exhibited significantly low levels of antioxidant enzyme activity and expression (SOD, CAT, GPx and GR), as well as high MDA levels. Moreover, PbAc exposure downregulated Nfe212 and Homx1 mRNA expression and significantly increased inflammatory marker (TNF-α, IL-1β and NO) levels in renal tissue. PbAc significantly upregulated the synthesis of apoptotic related proteins and downregulated antiapoptotic protein expression. Notably, LUT pretreatment of PbAc-treated rats provided significant nephroprotection and reversed the alterations in the abovementioned parameters. In conclusion, LUT provided significant protection against PbAc intoxication via antioxidant, anti-inflammatory, and anti-apoptotic activities by activating the Nrf2/ARE signaling pathway.

摘要

铅(Pb)是影响生物机体的最常见重金属污染物之一。它会导致肾毒性,使肾脏结构和功能发生重大变化。木犀草素(LUT)是一种存在于多种植物产品中的类黄酮,以表现出多种药理特性而闻名。我们评估了 LUT 对雄性 Wistar 大鼠 Pb 诱导肾损伤的保护作用。四个实验组:对照组、LUT(50mg/kg,口服)、PbAc(20mg/kg,ip)、LUT+PbAc(上述剂量),持续 7 天。PbAc 给药显著增加了肾脏中的 Pb 蓄积、血清中的尿素和肌酐水平,并诱导了肾脏组织学改变。此外,与对照组大鼠相比,PbAc 处理的大鼠的抗氧化酶活性和表达(SOD、CAT、GPx 和 GR)显著降低,MDA 水平升高。此外,PbAc 暴露下调了 Nfe212 和 Homx1 mRNA 的表达,并显著增加了肾脏组织中炎症标志物(TNF-α、IL-1β 和 NO)的水平。PbAc 显著上调了凋亡相关蛋白的合成,下调了抗凋亡蛋白的表达。值得注意的是,LUT 预处理 PbAc 处理的大鼠通过激活 Nrf2/ARE 信号通路,提供了对 PbAc 中毒的显著肾保护作用,并逆转了上述参数的变化。总之,LUT 通过抗氧化、抗炎和抗凋亡作用,为对抗 PbAc 中毒提供了显著的保护。

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