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绿茶(EGCG)和红葡萄白藜芦醇的肾脏保护作用评价:氧化应激和细胞因子的作用。

Evaluation of renal protective effects of the green-tea (EGCG) and red grape resveratrol: role of oxidative stress and inflammatory cytokines.

机构信息

Department of Biochemistry, Faculty of Pharmacy, Mansoura University, Mansoura, Egypt.

出版信息

Nat Prod Res. 2011 Apr;25(8):850-6. doi: 10.1080/14786419.2010.533669.

Abstract

Epigallocatechin-gallate (EGCG) and resveratrol (RSVL) are two of the most promising natural medicines. We verified their capacity to ameliorate cisplatin (CP)-induced disruption of renal glomerular filtration rate (GFR) in rats, and sought the mediatory involvement of lipid peroxidation (malondialdehyde [MDA]-level) and inflammatory cytokine (TNF-α) therein. CP (10 mg kg⁻¹), a single i.p. dose, disrupted GFR (11-fold-rise in proteinuria, 2-5-fold rise in serum creatinine/urea levels) after 7 days, and killed all animals after 10 days. Kidney-homogenates from CP-treated rats displayed higher MDA and TNF-α, but lower reduced-glutathione (GSH) levels. Rats treated with EGCG (50 mg kg⁻¹, but not 25 mg kg⁻¹) had no fatalities and showed significantly-recovered GFR; while their kidney-homogenates had markedly reduced MDA, TNF-α and enhanced GSH levels at 7 days. Conversely, RSVL or quercetin (25, 50 mg kg⁻¹) neither improved GFR nor reduced (MDA)/TNF-α levels after 7 days. Resuming treatment with 50 mg kg⁻¹ for 10 days rescued only 25% of animals (p > 0.05). Correlation studies showed a significant association between creatinine level, and each of MDA (r = 0.91), GSH (r = -0.87), and TNF-α (0.91). The study showed for the first time that EGCG, unlike RSVL, can protect against CP-induced nephrotoxicity. At the molecular level, CP triggers a high level of oxidative stress and systemic inflammation, events that were all abrogated with EGCG; better than RSVL or quercetin.

摘要

没食子儿茶素没食子酸酯 (EGCG) 和白藜芦醇 (RSVL) 是两种最有前途的天然药物。我们验证了它们改善顺铂 (CP) 诱导的大鼠肾小球滤过率 (GFR) 破坏的能力,并寻找其中脂质过氧化 (丙二醛 [MDA] 水平) 和炎症细胞因子 (TNF-α) 的介导作用。CP(10mgkg-1),单次腹腔注射,7 天后 GFR 受损(蛋白尿增加 11 倍,血清肌酐/尿素水平增加 2-5 倍),10 天后所有动物死亡。CP 治疗大鼠的肾匀浆显示 MDA 和 TNF-α 升高,而还原型谷胱甘肽 (GSH) 水平降低。EGCG(50mgkg-1,但不是 25mgkg-1)治疗的大鼠没有死亡,GFR 明显恢复;而它们的肾匀浆在 7 天时 MDA、TNF-α 明显降低,GSH 水平明显升高。相反,RSVL 或槲皮素 (25、50mgkg-1) 治疗 7 天后既不能改善 GFR,也不能降低 (MDA)/TNF-α 水平。重新用 50mgkg-1 治疗 10 天仅挽救了 25%的动物(p>0.05)。相关性研究显示肌酐水平与 MDA(r=0.91)、GSH(r=-0.87)和 TNF-α(0.91)均有显著相关性。该研究首次表明,EGCG 与 RSVL 不同,可预防 CP 诱导的肾毒性。在分子水平上,CP 引发高水平的氧化应激和全身炎症,这些事件都被 EGCG 阻断,优于 RSVL 或槲皮素。

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