Division of Biochemistry, Department of Pharmacology and GTMR Unit, College of Clinical Pharmacy, Taif University, Taif, 21974, Saudi Arabia; Department of Biochemistry, Faculty of Pharmacy, Al-Azhar University, Cairo, 11751, Egypt.
Division of Biochemistry, Department of Pharmacology and GTMR Unit, College of Clinical Pharmacy, Taif University, Taif, 21974, Saudi Arabia; Department of Biochemistry, Faculty of Pharmacy, Cairo University, Cairo, 11562, Egypt.
J Trace Elem Med Biol. 2019 Mar;52:74-82. doi: 10.1016/j.jtemb.2018.12.003. Epub 2018 Dec 7.
Cadmium is an extremely toxic pollutant that reaches human body through intake of the industrially polluted food and water as well as through cigarette smoking and exposure to polluted air. Cadmium accumulates in different body organs especially the liver. It induces tissue injury largely through inflammation and oxidative stress-based mechanisms. The aim of the current study was to investigate the ability of γ glutamyl cysteine (γGC) to protect against cadmium-induced hepatocellular injury employing Wistar rats as a mammalian model. The results of the current work indicated that γGC upregulated the level of the anti-inflammatory cytokine IL-10 and downregulated the levels of the pro-inflammatory cytokines (TNF-α, IL-6, and IL-1β) in the cadmium-exposed rats. In addition, γGC reduced the liver tissues cadmium content in the cadmium-treated rats, suppressed the cadmium-induced hepatocellular apoptosis and oxidative modifications of cellular DNA, lipids, and proteins. Additionally, γGC enhanced the antioxidant potential of the liver tissues in the cadmium-treated rats as evidenced by a remarkable increase in the activity of the antioxidant enzymes superoxide dismutase and glutathione peroxidase and significant increase in the levels of the total antioxidant capacity and reduced glutathione as well as a significant reduction in oxidized to reduced glutathione (GSSG/GSH) ratio. Moreover, it effectively improved liver cell integrity in the cadmium-treated rats as demonstrated by a significant reduction in the serum activity of the liver enzymes (ALT and AST) and amelioration of the cadmium-evoked histopathological alterations. Together, these findings underscore, for the first time, the alleviating effects of γGC against cadmium-induced hepatocellular injury that is potentially mediated through reduction of liver tissue cadmium content along with modulation of both hepatocellular redox status and inflammatory cytokines.
镉是一种极其有毒的污染物，它通过摄入受工业污染的食物和水、吸烟以及暴露在污染的空气中进入人体。镉在不同的身体器官中积累，尤其是肝脏。它主要通过炎症和氧化应激机制诱导组织损伤。本研究旨在探讨γ-谷氨酰半胱氨酸（γGC）在利用 Wistar 大鼠作为哺乳动物模型对抗镉诱导的肝细胞损伤中的作用。目前的工作结果表明，γGC 上调了抗炎细胞因子 IL-10 的水平，下调了暴露于镉的大鼠中促炎细胞因子（TNF-α、IL-6 和 IL-1β）的水平。此外，γGC 降低了镉处理大鼠肝脏组织中的镉含量，抑制了镉诱导的肝细胞凋亡和细胞 DNA、脂质和蛋白质的氧化修饰。此外，γGC 增强了镉处理大鼠肝脏组织的抗氧化能力，表现为抗氧化酶超氧化物歧化酶和谷胱甘肽过氧化物酶的活性显著增加，总抗氧化能力和还原型谷胱甘肽水平显著增加，氧化型谷胱甘肽与还原型谷胱甘肽（GSSG/GSH）比值显著降低。此外，它还有效地改善了镉处理大鼠的肝细胞完整性，表现为血清中肝脏酶（ALT 和 AST）的活性显著降低，以及镉引起的组织病理学改变得到改善。总之，这些发现首次强调了 γGC 对镉诱导的肝细胞损伤的缓解作用，其潜在机制可能是通过降低肝脏组织中的镉含量，以及调节肝细胞的氧化还原状态和炎症细胞因子。
