MELATONINS ANTIOXIDANT PROTECTION AGAINST DELTA-AMINOLEVULINIC-ACID INDUCED OXIDATIVE DAMAGE IN RAT CEREBELLUM

delta-aminolevulinic acid (ALA) promotes the generation of reactive ox ygen species (ROS). Accumulation of ALA, as occurs in acute intermitte nt porphyria (AIP), is a potential endogenous source of ROS, which can then exert oxidative damage to cell structures. In this work we inves tigated the role of pharmacological concentrations of melatonin on the deleterious effect of ALA and its effect on porphyrin biosynthesis. R at cerebellum incubations were carried out with either ALA (1.0 mM) to gether with increasing concentrations of melatonin (0.1-2.0 mM) or 2.0 mM melatonin together with varying ALA concentrations (0.05-2.0 mM) f or different times (1-4 hr). ALA-induced lipid peroxidation was signif icantly diminished by melatonin in a concentration-dependent manner. I n all conditions 2.0 mM melatonin restored malondialdehyde levels to c ontrol values. In incubations without ALA, melatonin markedly reduced (36-40%) the basal levels of lipid peroxidation when compared with the corresponding controls. ALA uptake and porphyrin accumulation were in creased 30% in incubations with 1.0-2.0 mM ALA for 4 hr in the presenc e of 2.0 mM melatonin, providing evidence for the involvement of ALA-p romoted ROS in the damage of enzymes related to porphyrin biosynthesis . These results are further support for the protective role of melaton in against oxidative damage induced by ALA; this protective action of melatonin is probably due to melatonin's antioxidant and free radical scavenger properties. The development of a new therapeutic approach fo r AIP patients employing melatonin alone or in combination with conven tional treatments should be considered.