关键词： ATPase, adenosine triphosphatase Bax, B-cell associated X protein Bcl-2, B-cell lymphoma 2 CAT, catalase EDTA, ethylenediaminetetraacetic acid EGCG, epigallocatechin gallate Fluoride G6PD, glucose 6-phosphate dehydrogenase GAPDH, glyceraldehyde 3 phosphate dehydrogenase GCSH, γ-glutamylcysteine synthetase heavy subunit GPx, glutathione peroxidase GR, glutathione reductase GST, glutathione S-transferease GSTM, glutathione S-transferase Mu HO-1, heme oxygenase-1 IL-6, interleukin-6 Keap-1, Kelch-like ECH-associated protein 1 Kidney Kim-1, kidney injury molecule-1 LOOH, lipid hydroperoxide NF-kB, Nuclear factor kappa B NaF, sodium fluoride Nrf2, nuclear factor erythroid-2 related factor-2 Oxidative stress PC, protein carbonyl ROS/RNS, reactive oxygen species/reactive nitrogen species Rat Reactive oxygen species SOD, superoxide dismutase TBARS, thiobarbituric acid reactive substances TNF-α, tumor necrosis factor-α TSH, total sulfhydryl groups

来  源：   DOI：10.1016/j.toxrep.2014.01.002   PDF(Sci-hub)   PDF(Pubmed)

Abstract：
Fluoride intoxication generates free radicals, causing oxidative stress that plays a critical role in the progression of nephropathy. In the present study, we hypothesized that epigallocatechin gallate (EGCG), found in green tea, protects the kidneys of rats treated with fluoride by preventing oxidative stress, inflammation, and apoptosis. Pretreatment of fluoride-treated rats with EGCG resulted in a significant normalization of creatinine clearance and levels of urea, uric acid, and creatinine. Fluoride intoxication significantly increased renal oxidative stress markers and decreased the levels of renal enzymatic and non-enzymatic antioxidants. In addition, renal NO, TNF-α, IL-6 and NF-κB were also increased in the renal tissue of fluoride-treated rats. Further, EGCG pretreatment produced a significant improvement in renal antioxidant status and reduced lipid peroxidation, protein carbonylation and the levels of inflammatory markers in fluoride-treated kidney. Similarly, mRNA and protein analyses showed that EGCG pretreatment normalized the renal expression of Nrf2/Keap1 and its downstream regulatory proteins in fluoride-treated rat kidney. EGCG also effectively attenuated fluoride-induced renal apoptosis by the up-regulation of anti-apoptotic proteins such as Bcl-2 and down-regulation of Bax, caspase-3, caspase-9 and cytochrome c. Histology and immunohistochemical observations of Kim-1 provided further evidence that EGCG effectively protects the kidney from fluoride-mediated oxidative damage. These results suggest that EGCG ameliorates fluoride-induced oxidative renal injury by activation of the Nrf2/HO-1 pathway.
摘要：
氟化物中毒会产生自由基,引起氧化应激，在肾病的进展中起关键作用。在本研究中,我们假设表没食子儿茶素没食子酸酯(EGCG)，在绿茶中发现，通过防止氧化应激来保护用氟化物治疗的大鼠的肾脏，炎症,和凋亡。用EGCG预处理氟化物处理的大鼠导致肌酐清除率和尿素水平显着正常化，尿酸,和肌酐。氟化物中毒显着增加了肾脏氧化应激标志物，并降低了肾脏酶和非酶抗氧化剂的水平。此外,肾NO,TNF-α,在氟处理的大鼠的肾组织中IL-6和NF-κB也增加。Further,EGCG预处理产生肾脏抗氧化状态的显著改善和减少脂质过氧化,蛋白质羰基化和氟化物处理肾脏的炎症标志物水平。同样，mRNA和蛋白质分析表明，EGCG预处理可使氟化物处理的大鼠肾脏中Nrf2/Keap1及其下游调节蛋白的肾脏表达正常化。EGCG还通过上调抗凋亡蛋白如Bcl-2和下调Bax，有效地减弱氟化物诱导的肾细胞凋亡。caspase-3，caspase-9和细胞色素c。Kim-1的组织学和免疫组织化学观察进一步证明EGCG有效保护肾脏免受氟化物介导的氧化损伤。这些结果表明，EGCG通过激活Nrf2/HO-1途径改善了氟化物诱导的氧化性肾损伤。
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