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 increased urinary excretion of the delta-aminolevulinic acid (ALA). Recently, 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 and in vivo effect of melatonin, a recently described antioxidative agent, on ALA-induced lipid peroxidation in rat liver and kidney was determined. 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, against ALA-induced lipid peroxidation in liver and kidney homogenates. In in vivo experiments as well, it was demonstrated that ALA (40 mg/kg)-induced lipid peroxidation in liver and kidney was reduced by acute melatonin (10 mg/kg) treatment. The results support the involvement of free radicals in ALA toxicity and show that in vitro and in vivo melatonin confers protection against this toxicity, likely due to the antioxidative capability of the indole.
Carneiro
R C
RC
Department of Cellular and Structural Biology, University of Texas at San Antonio, 78284-7762, USA.
Reiter
R J
RJ
D000447:Aldehydes / Q000378:metabolism; D000622:Aminolevulinic Acid / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D007668:Kidney / Q000187:drug effects / Q000378:metabolism*; D015227:Lipid Peroxidation / Q000187:drug effects*; D008054:Lipid Peroxides / Q000378:metabolism*; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D008550:Melatonin / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley
D000447:Aldehydes; D000975:Antioxidants; D008054:Lipid Peroxides; D008315:Malondialdehyde; D000622:Aminolevulinic Acid; D008550:Melatonin; C027576:4-hydroxy-2-nonenal