Salama Samir A, Arab Hany H, Maghrabi Ibrahim A, Hassan Memy H, AlSaeed Mohammed S
Department of Biochemistry, Faculty of Pharmacy, Al-Azhar University, Cairo, 11751, Egypt.
Divsion of Biochemistry, Department of Pharmacology and GTMR Unit, College of Clinical Pharmacy, Taif University, Taif, 21974, Saudi Arabia.
Biol Trace Elem Res. 2016 Sep;173(1):96-107. doi: 10.1007/s12011-016-0624-4. Epub 2016 Jan 15.
Lead is a biohazardous metal that is commonly involved in human illness including renal injury. Although it is a non-redox reactive metal, lead-induced renal injury is largely based on oxidative stress. The current work aimed at exploring the possible protective effect of γ-glutamyl cysteine (γGC) against lead-induced renal injury. Rats were allocated to normal and γGC control groups, lead-treated group, and lead and γGC-treated group. γGC alleviated lead-induced renal injury as evidenced by attenuation of histopathological aberration, amelioration of oxidative injury as demonstrated by significant reduction in lipid and protein oxidation, elevation of total antioxidant capacity, and glutathione level. The activity of antioxidant enzymes superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) was significantly elevated. γGC significantly decreased levels of the proinflammatory cytokines tumor necrosis factor-α (TNF-α), interleukin (IL)-6, and IL-1β and the activity of the apoptotic marker caspase-3. In addition, γGC reduced kidney lead content, enhanced weight gain, and improved renal function as demonstrated by reduced serum levels of urea and creatinine. Importantly, γGC upregulated proliferating cell nuclear antigen (PCNA) expression, denoting enhanced renal regenerative capacity. Together, our findings highlight evidence for alleviating effects of γGC against lead-induced renal injury that is potentially mediated through diminution of oxidative tissue injury, reduction of inflammatory response, attenuation of apoptosis, and enhancement of renal regenerative capacity.
铅是一种具有生物危害性的金属，常与包括肾损伤在内的人类疾病相关。尽管铅是一种非氧化还原活性金属，但铅诱导的肾损伤很大程度上基于氧化应激。当前的研究旨在探索γ-谷氨酰半胱氨酸（γGC）对铅诱导的肾损伤可能的保护作用。将大鼠分为正常组和γGC对照组、铅处理组以及铅与γGC处理组。γGC减轻了铅诱导的肾损伤，组织病理学异常的减轻、脂质和蛋白质氧化显著降低所表明的氧化损伤的改善、总抗氧化能力和谷胱甘肽水平的升高均证明了这一点。抗氧化酶超氧化物歧化酶（SOD）、过氧化氢酶（CAT）和谷胱甘肽过氧化物酶（GPx）的活性显著升高。γGC显著降低了促炎细胞因子肿瘤坏死因子-α（TNF-α）、白细胞介素（IL）-6和IL-1β的水平以及凋亡标志物半胱天冬酶-3的活性。此外，γGC降低了肾脏铅含量，促进了体重增加，并改善了肾功能，血清尿素和肌酐水平降低证明了这一点。重要的是，γGC上调了增殖细胞核抗原（PCNA）的表达，表明肾脏再生能力增强。总之，我们的研究结果突出了γGC对铅诱导的肾损伤具有缓解作用的证据，这可能是通过减少氧化组织损伤、减轻炎症反应、减弱细胞凋亡以及增强肾脏再生能力介导的。
