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表儿茶素补充通过线粒体保护防止反复暴露于镉的大鼠的肾脏损伤。

Catechin supplementation prevents kidney damage in rats repeatedly exposed to cadmium through mitochondrial protection.

机构信息

Renal Physiology Unit, Department of Physiology, Faculty of Medicine, Chiang Mai University, Chiang Mai, 50200, Thailand.

Mahidol University, Nakhonsawan Campus, Nakhonsawan, 60130, Thailand.

出版信息

Naunyn Schmiedebergs Arch Pharmacol. 2018 Apr;391(4):385-394. doi: 10.1007/s00210-018-1468-6. Epub 2018 Jan 22.

Abstract

Nephrotoxicity is recognized as a serious disorder affected by chronic cadmium exposure. Imbalance between radical generation and elimination is considered a critical factor involved in the initiation and progression of renal injury caused by this heavy metal. The present study investigated the possible protection by catechin, a natural phenolic antioxidant, against cadmium nephrotoxicity and elucidated its potential mechanism. Male Wistar rats were assigned to receive vehicle, cadmium (CdCl 2 mg/kg, i.p.) and cadmium plus catechin (25, 50, and 100 mg/kg, orally, respectively). After 4 weeks of treatment, rats exposed to cadmium demonstrated a marked rise in blood urea nitrogen and creatinine, a fall in creatinine clearance, and renal pathologies like severe tubular damage, apoptosis, and abnormal mitochondrial structure. Significant increases in malondialdehyde, nitric oxide, and tumor necrosis factor-alpha, while reductions in antioxidant thiols, superoxide dismutase, and catalase, were also detected in the kidney tissues of cadmium-intoxicated rats. These alterations were associated with mitochondrial dysfunction as supported by an increase in mitochondrial reactive oxygen species production and a decline in mitochondrial membrane potential. Treatment with catechin significantly attenuated all the changes caused by cadmium. These findings suggest that catechin effectively protects the kidney against toxic effect of cadmium, presumably through its antioxidant, anti-inflammation, and mitochondrial protection. The study outcomes not only add evidence to reinforce the medical benefits of catechin but also, most importantly, give rise to a prospect of developing renal preventive strategy for individuals who are at risk of cadmium contamination by means of catechin supplementation.

摘要

肾毒性被认为是一种由慢性镉暴露引起的严重疾病。自由基的产生和消除失衡被认为是重金属引起的肾损伤发生和进展的一个关键因素。本研究探讨了儿茶素(一种天然酚类抗氧化剂)对镉肾毒性的可能保护作用,并阐明了其潜在机制。雄性 Wistar 大鼠被分为接受载体、镉(CdCl 2 2mg/kg,腹腔注射)和镉加儿茶素(分别为 25、50 和 100mg/kg,口服)。经过 4 周的治疗,暴露于镉的大鼠表现出血尿素氮和肌酐明显升高、肌酐清除率下降以及严重的肾小管损伤、细胞凋亡和异常线粒体结构等肾脏病变。镉中毒大鼠的肾脏组织中还检测到丙二醛、一氧化氮和肿瘤坏死因子-α显著增加,而抗氧化硫醇、超氧化物歧化酶和过氧化氢酶减少。这些变化与线粒体功能障碍有关,因为线粒体活性氧的产生增加,线粒体膜电位下降。儿茶素治疗显著减轻了镉引起的所有变化。这些发现表明,儿茶素通过其抗氧化、抗炎和线粒体保护作用,有效地保护肾脏免受镉的毒性影响。该研究结果不仅为儿茶素的医学益处提供了更多证据,而且最重要的是为开发针对因镉污染而处于风险中的个体的肾脏预防策略提供了一个前景,即通过儿茶素补充来实现。

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