title: Effect of melatonin administration on DNA damage and repair responses in lymphocytes of rats subchronically exposed to lead.
abstract: Lead exposure induces DNA damage, oxidative stress, and apoptosis, and alters DNA repair. We investigated the effects of melatonin co-administered to rats during exposure to lead. Three doses of lead acetate (10, 50 and 100mg/kg/day) were administered to rats during a 6-week period. Lymphocytes were analyzed. Lead exposure decreased glutathione (GSH) levels in blood, and at doses of 100mg/kg/day and 50mg/kg/day without melatonin, caused high levels of DNA damage, induced apoptosis, and altered DNA repair. Melatonin co-treatment did not attenuate the effects of lead at 100mg/kg/day, indicating that the effect of melatonin on GSH reduction is not sufficient to reduce the genotoxic effects of lead at this high dose. After 6 weeks of treatment, decreased weight gain was observed in high lead-dose groups (100mg/kg/day), with or without melatonin, and in medium-dose groups (50mg/kg/day) with melatonin, compared with the control group. The protective action of melatonin against lead toxicity is dependent on the dose of lead. Further pharmacological studies are needed to determine whether melatonin acts via melatonin membrane receptors on lymphocytes.
authors.affiliation: Department of Pharmacy, University of Guanajuato, Guanajuato, México 36050, Mexico. alfarominerva@yahoo.fr
authors.forename: Minerva
authors.initials: M
authors.lastname: Martínez-Alfaro
authors.forename: Daniel
authors.initials: D
authors.lastname: Hernández-Cortés
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Wrobel
authors.forename: Gustavo
authors.initials: G
authors.lastname: Cruz-Jiménez
authors.forename: Julio Cesar
authors.initials: JC
authors.lastname: Rivera-Leyva
authors.forename: Rosa María
authors.initials: RM
authors.lastname: Piña-Zentella
authors.forename: Alfonso
authors.initials: A
authors.lastname: Cárabez Trejo
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D020552:Comet Assay; D004249:DNA Damage / Q000187:drug effects*; D004260:DNA Repair / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D005979:Glutathione Peroxidase / Q000378:metabolism; D008214:Lymphocytes / Q000378:metabolism; D008550:Melatonin / Q000494:pharmacology*; D009942:Organometallic Compounds / Q000008:administration & dosage / Q000633:toxicity*; D051381:Rats; D017208:Rats, Wistar
chemical_list: D009942:Organometallic Compounds; D005979:Glutathione Peroxidase; D008550:Melatonin; C008261:lead acetate