MELATONIN REDUCES BOTH BASAL AND BACTERIAL LIPOPOLYSACCHARIDE-INDUCEDLIPID-PEROXIDATION IN-VITRO

The protective effect of melatonin against lipopolysaccharide (LPS)-in duced oxidative damage was examined in vitro. Lung, liver, and brain m alonaldehyde (MDA) plus 4-hydroxyalkenals (4-HDA) concentrations were measured as indices of induced membrane peroxidative damage. Homogenat es of brain, lung, and liver were incubated with LPS at concentrations of either 1, 10, 50, 200, or 400 mu g/ml for 1 h and, in another stud y, LPS at a concentration of 400 mu g/ml for either 0, 15, 30, or 60 m in. Melatonin at increasing concentrations from 0.01-3 mM either alone or together with LPS (400 mu g/ml) was used. Liver, brain, and lung M DA + 4-HDA levels increased after LPS at concentrations of 10, 50, 200 or 400 mu g/ml; this effect was concentration-dependent. The highest levels of lipid peroxidation products were observed after tissues were incubated with an LPS concentration of 400 mu g/ml for 60 min; in liv er and lung this effect was totally suppressed by melatonin and partia lly suppressed in brain in a concentration-dependent manner. In additi on, melatonin alone was effective in brain at concentrations of 0.1 to 3 mM, in lung at 2 to 3 mM, and in liver at 0.1 to 3 mM; in all cases , the inhibitory effects of melatonin on lipid peroxidation were alway s directly correlated with the concentration of melatonin in the mediu m. The results show that the direct effect of LPS on the lipid peroxid ation following endotoxin exposure is markedly reduced by melatonin.