DELTA-AMINOLEVULINIC ACID-INDUCED LIPID-PEROXIDATION IN RAT-KIDNEY AND LIVER IS ATTENUATED BY MELATONIN - AN IN-VITRO AND IN-VIVO STUDY

Acute intermittent porphyria (AIP) is a genetically inherited disease characterized by a partial block in liver heme biosynthesis and by inc reased urinary excretion of the delta-aminolevulinic acid (ALA). Recen tly, it has been proposed that the toxic effects of ALA are related to the generation of free radicals. In the present study the in vitro an d in vivo effect of melatonin, a recently described antioxidative agen t, on ALA-induced lipid peroxidation in rat liver and kidney was deter mined. The concentration of malonaldehyde (MDA) and 4-hydroxyalkenals (4-HDA) was assayed as an index of induced membrane oxidative damage. In vitro melatonin protected, in a concentration-dependent manner, aga inst ALA-induced lipid peroxidation in liver and kidney homogenates. I n in vivo experiments as well, it was demonstrated that ALA (40 mg/kg) -induced lipid peroxidation in liver and kidney was reduced by acute m elatonin (10 mg/kg) treatment. The results support the involvement of free radicals in ALA toxicity and show that in vitro and in vivo melat onin confers protection against this toxicity, likely due to the antio xidative capability of the indole.