MELATONIN COUNTERACTS LIPID-PEROXIDATION INDUCED BY CARBON-TETRACHLORIDE BUT DOES NOT RESTORE GLUCOSE-6 PHOSPHATASE-ACTIVITY

Carbon tetrachloride (CCl4) exerts its toxic effects by the generation of free radicals. In this study we investigated whether melatonin, a potent free radical scavenger, could prevent the deleterious effects o f CCl4. Liver homogenates and liver microsomes were incubated with CCl 4 in the presence of melatonin and lipid peroxidation and glucose-6 ph osphatase (G6Pase) activity were determined. All doses of CCl4 (1, 0.5 , 0.1 mM) produced significantly high levels of lipid peroxidation, as reflected by increased levels of malonaldehyde and 4-hydroxyalkenals, in both liver homogenates and liver microsomes. These doses of CCl4 c oncommitantly reduced the activity of microsomal G6Pase. Go-incubation with melatonin dose-dependently (2, 1, 0.5 mM) inhibited the producti on of lipid peroxidation, but it was unable to restore the activity of G6Pase. In in vivo studies, rats were also treated with melatonin (10 mg/kg, i.p.), given 30 min before and 60 min after the administration of CCl4 (5 ml/kg, i.p.). Significantly elevated levels of lipid perox idation were measured in the liver and kidney. Melatonin prevented the CCl4-induced lipid peroxidation in the kidney, bur not in the liver. These data suggest that melatonin may provide protection against some of the damaging effects of CCl4, possibly due to its ability to scaven ge toxic free radicals.