Effect of melatonin administration on DNA damage and repair responses in lymphocytes of rats subchronically exposed to lead

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 100 mg/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 100 mg/kg/day and 50 mg/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 100 mg/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 (100 mg/kg/day), with or without melatonin, and in medium-dose groups (50 mg/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.

► Lead effects.
► Oxidative stress.
► Melatonin reduce oxidative stress effect.
► Melatonin reduces lead effects in vivo.
► Melatonin effects are dependent on lead dose.