Autoxidation and toxicant-induced oxidation of lipid and DNA in monkey liver: Reduction of molecular damage by melatonin

Melatonin, the main secretory product of the pineal gland, is a free radical scavenger and antioxidant which protects against oxidative damage due to a variety of toxicants. However, there is little information regarding melatonin's antioxidative capacity in tissues of primates. In this study we examined the protective effects of melatonin in monkey liver homogenates against lipid damage that occurred as a result of autoxidation or that induced by exogenous addition of H₂O₂ and ferrous iron (Fe²⁺). Additionally, we tested melatonin's protective effect against oxidative damage to DNA induced by chromium(III) (CrIII) plus H₂O₂. The levels of malondialdehyde and 4-hydroxyalkenals were assayed as an index of lipid peroxidation, and the concentrations of 8-hydroxydeoxyguanosine (8-OHdG) as an endpoint of oxidative DNA damage. The increases in malondialdehyde +4-hydroxyalkenals concentrations as a consequence of autoxidation or after the addition of H₂O₂ plus Fe²⁺ to the homogenates were time-dependent. The accumulation of these damaged products due to either autoxidative processes or induced by H₂O₂ and Fe²⁺ were significantly reduced by melatonin in a concentration-dependent-manner. The levels of 8-OHdG were elevated in purified monkey liver DNA incubated with a combination of CrCl₃ plus H₂O₂. This rise in oxidatively damaged DNA was prevented by 10 μM concentration of melatonin. Also, melatonin reduced the damage to DNA that was caused by autoxidative processes. These findings in monkey liver tissue document the ability of melatonin to protect against oxidative damage to both lipid and DNA in primate tissue, as observed previously in rodent tissue. The findings provide support for the use of melatonin as suitable agent to reduce damage inflicted by free radical species in primates.