Melatonin protects against δ-aminolevulinic acid-induced oxidative damage in male Syrian hamster Harderian glands

Abstract

Effects of the prooxidant δ-aminolevulinic acid (ALA) and the antioxidant melatonin (MEL) were investigated in the male Syrian hamster Harderian gland (HG). Rodent Harderian glands are highly porphyrogenic organs, which may be used as model systems for studying damage by δ-aminolevulinic acid and its metabolites, as occurring in porphyrias. Chronic administration of δ-aminolevulinic acid (2 weeks) markedly decreased activities of the porphyrogenic enzymes δ-aminolevulinate synthase (ALA-S) and δ-aminolevulinate dehydratase (ALA-D) and of the antioxidant enzymes superoxide dismutase (SOD), glutathione reductase (GR) and catalase (CAT), whereas porphobilinogen deaminase (PBG-D) remained unaffected. This treatment led to increased lipid peroxidation (LPO) and oxidatively modified protein (protein carbonyl) as well as to morphologically apparent tissue damage. Melatonin also caused decreases in δ-aminolevulinate synthase, δ-aminolevulinate dehydratase, superoxide dismutase, glutathione reductase and catalase. Despite lower activities of antioxidant enzymes, lipid peroxidation and protein carbonyl were markedly diminished. The combination of δ-aminolevulinic acid and melatonin led to approximately normal levels of δ-aminolevulinate dehydratase, glutathione reductase, catalase and protein carbonyl, and to rises in superoxide dismutase and porphobilinogen deaminase activities; lipid peroxidation remained even lower than in controls and the appearance of the tissue revealed a protective influence of melatonin. These results suggest that melatonin may have profound effects on the oxidant status of the Harderian gland.