title: Prophylactic efficacy of melatonin on cyclophosphamide-induced liver toxicity in mice.
abstract: The current study aimed to evaluate the protective effects of melatonin, a pineal secretory product, against hepatotoxicity induced by cyclophosphamide (CP) in mice. Mice were pretreated with melatonin intraperitoneally for 7 consecutive days before the administration of a single intraperitoneal dose of 200 mg/kg CP. 24 hr after CP administration, the mice were anesthetized, blood was then removed, and serum toxicity enzymes activities were evaluated. After the blood sampling, all animals were killed, livers were then removed, and histological studies were conducted. Serum toxicity marker enzymes were significantly increased after CP treatment but restored in melatonin pretreated groups. In addition, administration of CP induced necrotic hepatocyte with small crushed nuclei, portal space with severe inflammation, and hepatocytes surrounded by lymphocytic infiltration in hepatic tissues. However, melatonin effectively protected against CP-induced histopathological abnormalities in the liver tissues. Our results reveal that melatonin produces a potent hepatoprotective mechanism against CP. Therefore, melatonin could be a potent candidate to use concomitantly as a supplement agent against hepatotoxicity of CP for the patients undergoing chemotherapy.
authors.affiliation: Pharmaceutical Sciences Research Center, Faculty of Pharmacy, Mazandaran University of Medical Sciences, 18 Kilometers of Farah Abad Road, Sari 48175-861, Iran ; Department of Toxicology and Pharmacology, Faculty of Pharmacy, Mazandaran University of Medical Sciences, 18 Kilometers of Farah Abad Road, Sari 48175-861, Iran.
authors.forename: Mohammad
authors.identifier: 0000-0002-9679-7370
authors.initials: M
authors.lastname: Shokrzadeh
authors.affiliation: Pharmaceutical Sciences Research Center, Faculty of Pharmacy, Mazandaran University of Medical Sciences, 18 Kilometers of Farah Abad Road, Sari 48175-861, Iran.
authors.forename: Amirhossein
authors.initials: A
authors.lastname: Ahmadi
authors.affiliation: Department of Pathology, Faculty of Medicine, Mazandaran University of Medical Sciences, 18 Kilometers of Farah Abad Road, Sari 48175-861, Iran.
authors.forename: Farshad
authors.initials: F
authors.lastname: Naghshvar
authors.affiliation: Student Research Committee, Mazandaran University of Medical Sciences, 18 Kilometers of Farah Abad Road, Sari 48175-861, Iran.
authors.forename: Aroona
authors.initials: A
authors.lastname: Chabra
authors.affiliation: Department of Pathology, Faculty of Medicine, Mazandaran University of Medical Sciences, 18 Kilometers of Farah Abad Road, Sari 48175-861, Iran.
authors.forename: Mehdi
authors.initials: M
authors.lastname: Jafarinejhad
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000008:administration & dosage; D056486:Chemical and Drug Induced Liver Injury / Q000188:drug therapy* / Q000473:pathology; D003520:Cyclophosphamide / Q000633:toxicity*; D015227:Lipid Peroxidation / Q000187:drug effects; D008099:Liver / Q000187:drug effects; D008550:Melatonin / Q000008:administration & dosage*; D051379:Mice; D018384:Oxidative Stress / Q000187:drug effects; D020011:Protective Agents / Q000008:administration & dosage*
chemical_list: D000975:Antioxidants; D020011:Protective Agents; D003520:Cyclophosphamide; D008550:Melatonin
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