Dun-Xian Tan — Page 3 | Search PubMed

PubMed2000

Melatonin suppresses autoxidation and hydrogen peroxide-induced lipid peroxidation in monkey brain homogenate.

OBJECTIVES: Melatonin, the major secretory product of the pineal gland, is known as an effective antioxidant and neuroprotector. Its neuroprotective actions and mechanisms have been documented in a variety of rodent brain models. However, little is known of melatonin's antioxidative capacity in the brain of primates. Herein, we investigated whether melatonin would suppress autoxidation and exogenous hydrogen peroxide-induced lipid peroxidation in monkey cerebral cortical homogenates. MATERIALS AND METHODS: The monkey brain was dissected during routine autopsy and immediately frozen at -80 degrees C until the experiment. A sample of cerebral cortex (50 mg) was homogenized in 1 ml ice cold phosphate buffer (20 mM, pH 7.4) at 0-4 degrees C. Four different treatments of cerebral cortical homogenates were performed: 1) homogenates incubated in a water bath at different temperatures (4 degrees C, 25 degrees C or 37 degrees C, respectively) for two hours to induce autoxidation; 2) homogenates co-incubated with different concentrations of melatonin at 37 degrees C for 2 hours; 3) homogenates co-incubated with 1 mM vitamin C and different concentrations of hydrogen peroxide at 37 degrees C for 1 hour to induce membrane lipid peroxidation; 4) homogenates incubated with different concentrations of melatonin and 1 mM H2O2 plus 1 mM vitamin C. After incubation, homogenates were analyzed for products of lipid peroxidation (malondialdehyde and 4-hydroxy-alkenals). RESULTS: The levels of lipid peroxidation products significantly increased in monkey cerebral cortical homogenates as a consequence of autoxidation or after the addition of H2O2 plus vitamin C. Melatonin not only suppressed the increase in lipid peroxidation induced by H2O2 plus vitamin C but also inhibited lipid breakdown resulting from autoxidation. The concentrations of melatonin required to suppress lipid peroxidation resulting from autoxidation or induced by exogenous oxidants in monkey cerebral cortical homogenates were in the same dose range. CONCLUSION: The results show for the first time that melatonin functions as an antioxidant and neuroprotector in primate brain tissue as was observed previously in rodent brain. The data provide information supporting the use of melatonin in the treatment of neurodegenerative disorders that involve oxidative damage to brain lipids.

Journal Article↗

PubMedDate not supplied

Pharmacological utility of melatonin in reducing oxidative cellular and molecular damage.

This review briefly summarizes the actions of melatonin in reducing molecular damage caused by free radicals and associated oxygen- and nitrogen-based reactants. All the mechanisms by which melatonin is protective of such a wide variety of molecules, i.e. lipids, proteins, DNA, etc., and in such widely diverse areas of the cell and different organs are likely not yet all identified. Melatonin actions that have been identified include its ability to directly neutralize a number of toxic reactants and stimulate antioxidative enzymes. Furthermore, several metabolites that are formed when melatonin neutralizes damaging reactants are themselves scavengers suggesting that there is a cascade of reactions that greatly increase the efficacy of melatonin in styming oxidative mutilation. Suggested, but less well defined, processes which may contribute to melatonin's ability to reduce oxidative stress include stimulation of glutathione synthesis (an important antioxidant which is at high concentrations within cells), reducing electron leakage from the mitochondrial electron transport chain (which would reduce free radical generation), limiting cytokine production and inflammatory processes (actions that would also lower toxic reactant generation), and synergistic effects with other classical antioxidants (e.g. vitamins C, E and glutathione). Clearly which of these multiple mechanisms contribute to melatonin's high efficacy in curtailing oxidative damage remains to be clarified. Likewise, it is possible that the key action of melatonin in reducing molecular damage induced by oxygen and nitrogen-based metabolites remains to be identified. Finally, the review summarizes some of the large amount of data documenting the ability of melatonin to limit molecular and organ damage in two situations, i.e. ischemia-reperfusion and ionizing radiation, where free radicals are generally conceded as being responsible for much of the resulting tissue destruction.

Animals↗