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Luteolin protects against lead acetate-induced nephrotoxicity through antioxidant, anti-inflammatory, anti-apoptotic, and Nrf2/HO-1 signaling pathways.
Molecular Biology Reports ( IF 2.8 ) Pub Date : 2020-03-07 , DOI: 10.1007/s11033-020-05346-1
Alaa Jameel A Albarakati 1 , Roua S Baty 2 , Ahmad M Aljoudi 3 , Ola A Habotta 4 , Ehab K Elmahallawy 5, 6 , Rami B Kassab 7 , Ahmed E Abdel Moneim 7
Affiliation  

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.

中文翻译:

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

铅(Pb)是影响生物的最常见的重金属污染物之一。它诱导肾毒性,肾结构和功能发生重大变化。木犀草素(LUTolin)是一种存在于多种植物产品中的类黄酮,因具有多种药理特性而广为人知。我们评估了LUT对雄性Wistar大鼠中铅引起的肾损伤的保护作用。四个实验组:对照组,LUT(50 mg / kg,口服),PbAc(20 mg / kg,腹膜内),LUT + PbAc(以上述剂量)维持7天。服用PbAc会显着增加血清中的肾脏Pb积累,尿素和肌酐水平,并引起肾脏组织学改变。此外,与对照组大鼠相比,用PbAc处理的大鼠的抗氧化酶活性和表达水平明显较低(SOD,CAT,GPx和GR),以及较高的MDA水平。此外,PbAc暴露下调了肾组织中Nfe212和Homx1 mRNA的表达,并显着增加了炎症标志物(TNF-α,IL-1β和NO)的水平。PbAc明显上调凋亡相关蛋白的合成,并下调抗凋亡蛋白的表达。值得注意的是,对PbAc处理的大鼠进行LUT预处理可提供明显的肾保护作用,并逆转上述参数的变化。总之,LUT通过激活Nrf2 / ARE信号通路,通过抗氧化,抗炎和抗凋亡活性,提供了针对PbAc中毒的有效保护。肾组织中的IL-1β和NO)水平。PbAc显着上调凋亡相关蛋白的合成,并下调抗凋亡蛋白的表达。值得注意的是,对PbAc处理的大鼠进行LUT预处理可提供明显的肾保护作用,并逆转上述参数的变化。总之,LUT通过激活Nrf2 / ARE信号通路,通过抗氧化,抗炎和抗凋亡活性,提供了针对PbAc中毒的有效保护。肾组织中的IL-1β和NO)水平。PbAc显着上调凋亡相关蛋白的合成,并下调抗凋亡蛋白的表达。值得注意的是,对PbAc处理的大鼠进行LUT预处理可提供明显的肾保护作用,并逆转上述参数的变化。总之,LUT通过激活Nrf2 / ARE信号通路,通过抗氧化剂,抗炎和抗凋亡活性,提供了针对PbAc中毒的有效保护。
更新日期:2020-03-09
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