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EGCG 经腹腔注射对糖尿病小鼠的肾毒性作用:氧化应激、炎症和细胞凋亡的参与。

Nephro-toxic effects of intraperitoneally injected EGCG in diabetic mice: involvement of oxidative stress, inflammation and apoptosis.

机构信息

Department of Pharmacology and Toxicology, Faculty of Pharmacy, Cairo University, Egypt.

出版信息

Sci Rep. 2017 Jan 18;7:40617. doi: 10.1038/srep40617.

Abstract

Epigallocatechin gallate (EGCG) has been studied for its beneficial effects. However, some case reports have associated EGCG supplementation with hepato-toxicity. In the present study, we investigated the possible nephro-toxic effects of EGCG in diabetic mice. Streptozotocin (150 mg/kg, i.p.) was injected in mice for diabetes induction. EGCG (100 mg/kg/day, i.p.) was then given for 4 days. The administration of EGCG to diabetic mice caused 60% mortality with no death recorded in other groups. Blood samples were collected for estimation of serum cystatin C, neutrophil gelatinase-associated lipocalin and blood urea nitrogen. Animals were then sacrificed and kidneys were rapidly excised for estimation of oxidative stress markers (NADPH oxidase, reduced glutathione, total antioxidant capacity, nuclear factor erythroid 2-related factor 2, heat shock protein 90, hemeoxygenase-1), as well as inflammatory markers (nuclear factor kappa-B and tumor necrosis factor-α). Administration of EGCG to diabetic mice showed significant elevation in serum cystatin C and neutrophil gelatinase-associated lipocalin, marked increase in oxidative stress and inflammatory states in addition to marked over expression of active caspase-3. Histopathological examination confirmed EGCG induced renal damage in diabetic mice. In conclusion, despite of its well known favorable effects, EGCG could paradoxically exhibit nephro-toxic effect in the presence of diabetes.

摘要

没食子酸表没食子儿茶素酯(EGCG)已因其有益作用而受到研究。然而,一些病例报告将 EGCG 补充与肝毒性联系起来。在本研究中,我们研究了 EGCG 在糖尿病小鼠中可能的肾毒性作用。链脲佐菌素(150mg/kg,腹腔注射)用于诱导糖尿病。然后给予 EGCG(100mg/kg/天,腹腔注射)4 天。给予 EGCG 会使糖尿病小鼠的死亡率达到 60%,而其他组没有死亡记录。采集血样以估计血清胱抑素 C、中性粒细胞明胶酶相关脂质运载蛋白和血尿素氮。然后处死动物,迅速切除肾脏以评估氧化应激标志物(NADPH 氧化酶、还原型谷胱甘肽、总抗氧化能力、红细胞生成素相关因子 2、热休克蛋白 90、血红素加氧酶-1)以及炎症标志物(核因子 kappa-B 和肿瘤坏死因子-α)。给予 EGCG 会使糖尿病小鼠的血清胱抑素 C 和中性粒细胞明胶酶相关脂质运载蛋白显著升高,氧化应激和炎症状态明显增加,同时活性 caspase-3 的过度表达。组织病理学检查证实 EGCG 在糖尿病小鼠中引起了肾损伤。总之,尽管 EGCG 具有众所周知的有利作用,但在糖尿病存在的情况下,它可能会表现出肾毒性作用。

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