title: Gamma-Glutamyl Cysteine Attenuates Tissue Damage and Enhances Tissue Regeneration in a rat Model of Lead-Induced Nephrotoxicity.
abstract: 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.
authors.affiliation: Department of Biochemistry, Faculty of Pharmacy, Al-Azhar University, Cairo, 11751, Egypt. salama.3@buckeyemail.osu.edu.|Divsion of Biochemistry, Department of Pharmacology and GTMR Unit, College of Clinical Pharmacy, Taif University, Taif, 21974, Saudi Arabia. salama.3@buckeyemail.osu.edu.
authors.forename: Samir A
authors.initials: SA
authors.lastname: Salama
authors.affiliation: Divsion 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.
authors.forename: Hany H
authors.initials: HH
authors.lastname: Arab
authors.affiliation: Department of Clinical Pharmacy, College of Clinical Pharmacy, Taif University, Al-Haweiah, Taif, 21974, Saudi Arabia.
authors.forename: Ibrahim A
authors.initials: IA
authors.lastname: Maghrabi
authors.affiliation: Department of Pharmacology and Toxicology, College of Pharmacy, Taibah University, El-Madinah El-Munaworah, 30001, Saudi Arabia.|Department of Pharmacology and Toxicology, Faculty of Pharmacy, Al-Azhar University, Cairo, 11231, Egypt.
authors.forename: Memy H
authors.initials: MH
authors.lastname: Hassan
authors.affiliation: Department of Surgery, College of Medicine, Taif University, Al-Haweiah, Taif, 21974, Saudi Arabia.
authors.forename: Mohammed S
authors.initials: MS
authors.lastname: AlSaeed
mesh_terms: D000818:Animals; D053148:Caspase 3 / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D004151:Dipeptides / Q000494:pharmacology*; D004195:Disease Models, Animal; D006801:Humans; D007674:Kidney Diseases / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D007855:Lead Poisoning / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D008297:Male; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D012038:Regeneration / Q000187:drug effects*
chemical_list: D016207:Cytokines; D004151:Dipeptides; D018809:Proliferating Cell Nuclear Antigen; C505410:Casp3 protein, rat; D053148:Caspase 3; C017341:gamma-glutamylcysteine
keywords: Glutamyl cysteine; Inflammation; Kidney injury; Lead toxicity; Oxidative stress