title: Melatonin attenuates phenytoin sodium-induced DNA damage.
abstract: Phenytoin sodium (PHT Na(+)) is a potent antiepileptic drug against epileptic seizures and is used as a prophylactic treatment in traumatic brain injury. PHT Na(+) leads to the formation of reactive oxygen species (ROS), and DNA is a crucial molecular target of ROS-initiated toxicity. Melatonin and its metabolites possess free-radical-scavenging activity. We therefore designed this study to investigate the potential protective effect of melatonin against PHT Na(+)-induced DNA damage by using the comet assay in a rat model in vivo. Thirty-three 3-month-old male Wistar rats were divided into five groups of control treated with isotonic sodium chloride (a single injection of isotonic sodium chloride and 100 µL in drinking water for 10 days), ethanol treated (in drinking water for 10 days containing 100 µL of ethanol in each 300-mL drinking bottle), melatonin treated (4 mg/kg body weight [b.w.] intraperitoneally [i.p.] at the start, in drinking water for 10 days), PHT Na(+) treated (a single i.p. injection of 50 mg/kg) and PHT Na(+) (50 mg/kg b.w., single i.p.) and melatonin (4 mg/kg b.w. i.p. at the start and 4 mg/kg in drinking water for 10 days) cotreated. To determine the protective effects of melatonin, the comet assay was performed using lymphocytes isolated in different time intervals (0, 15, 30, 45 and 60 minutes) from each group of animals. On days 1, 3, 7 and 10, blood samples were taken and the comet assay technique was performed. Our present data suggest that melatonin reversed PHT Na(+)-induced DNA damage.
authors.affiliation: Department of Pediatrics .
authors.forename: Ufuk
authors.initials: U
authors.lastname: Erenberk
authors.forename: Rusen
authors.initials: R
authors.lastname: Dundaroz
authors.forename: Ozlem
authors.initials: O
authors.lastname: Gok
authors.forename: Omer
authors.initials: O
authors.lastname: Uysal
authors.forename: Sami
authors.initials: S
authors.lastname: Agus
authors.forename: Adnan
authors.initials: A
authors.lastname: Yuksel
authors.forename: Bayram
authors.initials: B
authors.lastname: Yilmaz
authors.forename: Ulkan
authors.initials: U
authors.lastname: Kilic
mesh_terms: D000818:Animals; D000927:Anticonvulsants / Q000633:toxicity*; D020552:Comet Assay; D004249:DNA Damage / Q000187:drug effects*; D000431:Ethanol / Q000008:administration & dosage; D016166:Free Radical Scavengers / Q000494:pharmacology; D007274:Injections, Intraperitoneal; D008214:Lymphocytes / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008550:Melatonin / Q000494:pharmacology*; D018384:Oxidative Stress / Q000187:drug effects; D010672:Phenytoin / Q000633:toxicity*; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism; D013997:Time Factors
chemical_list: D000927:Anticonvulsants; D016166:Free Radical Scavengers; D017382:Reactive Oxygen Species; D000431:Ethanol; D010672:Phenytoin; D008550:Melatonin