title: Glutamyl cysteine dipeptide suppresses ferritin expression and alleviates liver injury in iron-overload rat model.
abstract: Despite its biological importance, iron is a pro-oxidant element and its accumulation results in tissue injury. Iron overload diseases such as thalassemia and hereditary hemochromatosis are commonly associated with liver tissue injury. Glutamyl cysteine (GC) is a dipeptide with antioxidant properties owing to its cysteine residue. The aim of the current work was to investigate the hepatoprotective effect of GC against iron overload-induced liver injury. Rats were distributed into five groups; normal control, GC control, iron-treated (150 mg/kg ip injection) and both iron and GC-treated (total iron: 150 mg/kg ip and GC: 50 mg or 100 mg/kg/day ip for 30 days). Our results showed that treatment with GC at the two-dose levels attenuated iron-induced liver tissue injury as evidenced by significant reduction in serum activity of liver enzymes ALT and AST, amelioration of iron-induced histopathological alteration, suppression of iron-induced oxidative stress as demonstrated by significant reduction of malondialdehyde and protein carbonyl content beside elevation of total antioxidant capacity, reduced glutathione and the antioxidant enzymes GPx and SOD in liver tissue. In addition, GC significantly reduced levels of the proinflammatory cytokines TNF-α, IL-6 and IL-1β and activity of the apoptotic marker caspase-3 in liver tissues. To our surprise, GC reduced liver iron content and ferritin expression, denoting the possible iron chelation competency. Collectively our results highlight evidence for the hepatoprotective effect of GC against iron overload-induced liver injury that is potentially mediated through suppression of oxidative tissue injury, attenuation of inflammatory response, amelioration of hepatocellular apoptosis and possibly through iron chelation.
authors.affiliation: 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. Electronic address: salama.3@buckeyemail.osu.edu.
authors.forename: Samir A
authors.initials: SA
authors.lastname: Salama
authors.affiliation: Department of Biology, College of Science, Taif University, Taif 21974, Saudi Arabia.
authors.forename: Mohammad S
authors.initials: MS
authors.lastname: Al-Harbi
authors.affiliation: Department of Pharmacology and Toxicology, Faculty of Pharmacy, Al-Azahr University, Cairo 11231, Egypt; Faculty of Pharmacy, Aljouf University, Aljouf, Saudi Arabia.
authors.forename: Mohamed S
authors.initials: MS
authors.lastname: Abdel-Bakky
authors.affiliation: Department of Pharmacology and Toxicology, Faculty of Pharmacy, Beni-Suef University, Beni-Suef 62514, Egypt; Sharjah Institute for Medical Research, College of Pharmacy, University of Sharjah, Sharjah 27272, United Arab Emirates.
authors.forename: Hany A
authors.initials: HA
authors.lastname: Omar
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology* / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects; D015415:Biomarkers / Q000378:metabolism; D053148:Caspase 3 / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D019610:Cytoprotection / Q000187:drug effects; D004151:Dipeptides / Q000494:pharmacology* / Q000627:therapeutic use; D005293:Ferritins / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000187:drug effects*; D007501:Iron / Q000378:metabolism; D019190:Iron Overload / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D008099:Liver / Q000187:drug effects* / Q000293:injuries* / Q000378:metabolism / Q000473:pathology; D008297:Male; D018384:Oxidative Stress / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar
chemical_list: D000975:Antioxidants; D015415:Biomarkers; D016207:Cytokines; D004151:Dipeptides; D005293:Ferritins; D007501:Iron; D053148:Caspase 3; C017341:gamma-glutamylcysteine
keywords: Glutamyl cysteine; Inflammation; Iron overload; Liver injury; Oxidative stress