title: Melatonin protects against delta-aminolevulinic acid-induced oxidative damage in male Syrian hamster Harderian glands.
abstract: Effects of the prooxidant delta-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 delta-aminolevulinic acid and its metabolites, as occurring in porphyrias. Chronic administration of delta-aminolevulinic acid (2 weeks) markedly decreased activities of the porphyrogenic enzymes delta-aminolevulinate synthase (ALA-S) and delta-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 delta-aminolevulinate synthase, delta-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 delta-aminolevulinic acid and melatonin led to approximately normal levels of delta-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.
authors.affiliation: Departamento de Morfología y Biología Celular, Universidad de Oviedo, E-33006 Oviedo, Asturias, Spain.
authors.forename: Cristina
authors.initials: C
authors.lastname: Tomás-Zapico
authors.forename: Jorge
authors.initials: J
authors.lastname: Martínez-Fraga
authors.forename: María Josefa
authors.initials: MJ
authors.lastname: Rodríguez-Colunga
authors.forename: Delio
authors.initials: D
authors.lastname: Tolivia
authors.forename: Rüdiger
authors.initials: R
authors.lastname: Hardeland
authors.forename: Ana
authors.initials: A
authors.lastname: Coto-Montes
mesh_terms: D000624:5-Aminolevulinate Synthetase / Q000378:metabolism; D000622:Aminolevulinic Acid / Q000494:pharmacology* / Q000633:toxicity; D000818:Animals; D002374:Catalase / Q000378:metabolism; D006224:Cricetinae; D005980:Glutathione Reductase / Q000378:metabolism; D006243:Harderian Gland / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology*; D015227:Lipid Peroxidation; D008297:Male; D008550:Melatonin / Q000494:pharmacology*; D008647:Mesocricetus; D010084:Oxidation-Reduction; D017319:Photosensitizing Agents / Q000494:pharmacology / Q000633:toxicity; D000623:Porphobilinogen Synthase / Q000378:metabolism; D013482:Superoxide Dismutase / Q000378:metabolism
chemical_list: D017319:Photosensitizing Agents; D000622:Aminolevulinic Acid; D002374:Catalase; D013482:Superoxide Dismutase; D005980:Glutathione Reductase; D000624:5-Aminolevulinate Synthetase; D000623:Porphobilinogen Synthase; D008550:Melatonin