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 radica l scavenger and antioxidant which protects against oxidative damage due to a variety of toxicants. However, there is little information regarding mela tonin's antioxidative capacity in tissues of primates. In this study we exa mined the protective effects of melatonin in monkey liver homogenates again st lipid damage that occurred as a result of autoxidation or that induced b y exogenous addition of H2O2 and ferrous iron (Fe2+). Additionally, we test ed melatonin's protective effect against oxidative damage to DNA induced by chromium(III) (CrIII) plus H2O2. The levels of malondialdehyde and 4-hydro xyalkenals were assayed as an index of lipid peroxidation, and the concentr ations of 8-hydroxydeoxyguanosine (8-OHdG) as an endpoint of oxidative DNA damage. The increases in malondialdehyde+4-hydroxyalkenals concentrations a s a consequence of autoxidation or after the addition of H2O2 plus Fe2+ to the homogenates were time-dependent. The accumulation of these damaged prod ucts 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 muM concentration of melatonin. Also, melatonin reduced th e damage to DNA that was caused by autoxidative processes. These findings i n monkey liver tissue document the ability of melatonin to protect against oxidative damage to both lipid and DNA in primate tissue, as observed previ ously in rodent tissue. The findings provide support for the use of melaton in as suitable agent to reduce damage inflicted by free radical species in primates.