title: Zinc Deficiency and Oxidative Stress Involved in Valproic Acid Induced Hepatotoxicity: Protection by Zinc and Selenium Supplementation.
abstract: Valproic acid (VPA) is an antiepileptic drug, which its usage is limited due to its hepatotoxicity. The present study was conducted to investigate the efficacy of zinc (Zn) and selenium (Se), necessary trace elements, against VPA-induced hepatotoxicity in Wistar rats. The animals were divided into five groups: control, VPA 200 mg/kg, VPA + Zn (100 mg/kg), VPA + Se (100 mg/kg), and VPA + Zn + Se. The administration of VPA for four consecutive weeks resulted in decrease in serum level of Zn in rats. Also, an increase in liver marker enzymes (ALT and AST) and also histological changes in liver tissue were shown after VPA administration. Oxidative stress was evident in VPA group by increased lipid peroxidation (LPO), protein carbonyl (PCO), glutathione (GSH) oxidation, and reducing total antioxidant capacity. Zn and Se (100 mg/kg) administration was able to protect against deterioration in liver enzyme, abrogated the histological change in liver tissue, and suppressed the increase in oxidative stress markers. Zn and combination of Zn plus Se treatment showed more protective effects than Se alone. These results imply that Zn and Se should be suggested as effective supplement products for the prevention of VPA-induced hepatotoxicity.
authors.affiliation: Pharmaceutical Sciences Research Center, Mazandaran University of Medical Sciences, Sari, Iran.|Department of Toxicology and Pharmacology, Faculty of Pharmacy, Mazandaran University of Medical Sciences, Sari, Iran.
authors.forename: Nematollah
authors.initials: N
authors.lastname: Ahangar
authors.affiliation: Pharmaceutical Sciences Research Center, Mazandaran University of Medical Sciences, Sari, Iran.|Department of Toxicology and Pharmacology, Faculty of Pharmacy, Mazandaran University of Medical Sciences, Sari, Iran.
authors.forename: Maloos
authors.initials: M
authors.lastname: Naderi
authors.affiliation: Pharmaceutical Sciences Research Center, Mazandaran University of Medical Sciences, Sari, Iran.|Department of Toxicology and Pharmacology, Faculty of Pharmacy, Mazandaran University of Medical Sciences, Sari, Iran.
authors.forename: Abdolali
authors.initials: A
authors.lastname: Noroozi
authors.affiliation: Faculty of Medicine, Immunogenetics Research Center, Mazandaran University of Medical Sciences, Sari, Iran.
authors.forename: Maryam
authors.initials: M
authors.lastname: Ghasemi
authors.affiliation: Pharmaceutical Sciences Research Center, Mazandaran University of Medical Sciences, Sari, Iran.|Department of Toxicology and Pharmacology, Faculty of Pharmacy, Mazandaran University of Medical Sciences, Sari, Iran.
authors.forename: Ehsan
authors.initials: E
authors.lastname: Zamani
authors.affiliation: Pharmaceutical Sciences Research Center, Mazandaran University of Medical Sciences, Sari, Iran. fshaki.tox@gmail.com.|Department of Toxicology and Pharmacology, Faculty of Pharmacy, Mazandaran University of Medical Sciences, Sari, Iran. fshaki.tox@gmail.com.
authors.forename: Fatemeh
authors.initials: F
authors.lastname: Shaki
mesh_terms: D000818:Animals; D019587:Dietary Supplements; D015227:Lipid Peroxidation / Q000187:drug effects; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D018384:Oxidative Stress / Q000187:drug effects*; D020011:Protective Agents / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D012643:Selenium / Q000008:administration & dosage / Q000494:pharmacology*; D014635:Valproic Acid / Q000008:administration & dosage / Q000633:toxicity*; D015032:Zinc / Q000008:administration & dosage / Q000172:deficiency* / Q000494:pharmacology*
chemical_list: D020011:Protective Agents; D014635:Valproic Acid; D012643:Selenium; D015032:Zinc
keywords: Liver; Oxidative stress; Selenium; Toxicity; Valproic acid; Zinc deficiency