Melatonin's antioxidant protection against delta-aminolevulinic acid-induced oxidative damage in rat cerebellum.
delta-aminolevulinic acid (ALA) promotes the generation of reactive oxygen species (ROS). Accumulation of ALA, as occurs in acute intermittent porphyria (AIP), is a potential endogenous source of ROS, which can then exert oxidative damage to cell structures. In this work we investigated the role of pharmacological concentrations of melatonin on the deleterious effect of ALA and its effect on porphyrin biosynthesis. Rat cerebellum incubations were carried out with either ALA (1.0 mM) together 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) for different times (1-4 hr). ALA-induced lipid peroxidation was significantly diminished by melatonin in a concentration-dependent manner. In all conditions 2.0 mM melatonin restored malondialdehyde levels to control 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 increased 30% in incubations with 1.0-2.0 mM ALA for 4 hr in the presence of 2.0 mM melatonin, providing evidence for the involvement of ALA-promoted ROS in the damage of enzymes related to porphyrin biosynthesis. These results are further support for the protective role of melatonin 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 for AIP patients employing melatonin alone or in combination with conventional treatments should be considered.
Princ
F G
FG
Departamento de Química Biológica, Facultad de Ciencias Exactas y Naturale Universidad de Buenos Aires, Argentina.
Juknat
A A
AA
Maxit
A G
AG
Cardalda
C
C
Batlle
A
A
D000622:Aminolevulinic Acid / Q000378:metabolism / Q000494:pharmacology*; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D002531:Cerebellum / Q000187:drug effects / Q000378:metabolism*; D015227:Lipid Peroxidation / Q000187:drug effects*; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D008550:Melatonin / Q000494:pharmacology*; D011166:Porphyrins / Q000378:metabolism; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism
D000975:Antioxidants; D011166:Porphyrins; D017382:Reactive Oxygen Species; D008315:Malondialdehyde; D000622:Aminolevulinic Acid; D008550:Melatonin