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AFMK, a melatonin metabolite, attenuates X‐ray‐induced oxidative damage to DNA, proteins and lipids in mice
Author(s) -
Manda Kailash,
Ueno Megumi,
Anzai Kazunori
Publication year - 2007
Publication title -
journal of pineal research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.881
H-Index - 131
eISSN - 1600-079X
pISSN - 0742-3098
DOI - 10.1111/j.1600-079x.2007.00432.x
Subject(s) - melatonin , chemistry , oxidative stress , dna damage , antioxidant , malondialdehyde , biochemistry , comet assay , lipid peroxidation , metabolite , protein carbonylation , oxidative phosphorylation , reactive oxygen species , hydroxyl radical , dna oxidation , dna , biology , endocrinology
Antioxidant function of melatonin is well established. However, N 1 ‐acetyl‐ N 2 ‐formyl‐5‐methoxykynuramine (AFMK), a melatonin metabolite is a sparingly investigated biogenic amine, especially in relation to its in vivo antioxidant function. We have evaluated the oxidative damage to biomolecules (DNA, protein and lipid) induced by X‐irradiation in C57BL mice and the prophylactic action of AFMK. The extent of DNA damage was analyzed by single‐cell gel electrophoresis in cerebral cortex and serum 8‐hydroxydeoxyguanosine (8‐OHdG) levels by enzyme‐linked immunosorbent assay. Oxidative modification of protein and lipid was measured in the terms of carbonyl content and 4‐HAE + MDA (4‐hydroxyalkenal + malondialdehyde) status of brain cortex. Radiation exposure dramatically augmented the level of 8‐OHdG in serum as well as DNA migration in the comet tail. AFMK pretreatment significantly inhibited DNA damage. In addition, radiation‐induced augmentation of protein carbonyl content and HAE + MDA was ameliorated by AFMK pretreatment. Whole‐body exposure of mice to X‐irradiation also reduced the level of brain sulfhydryl contents (protein‐bound sulfhydryl, total sulfhydryl, and nonprotein sulfhydryl) which were significantly protected by AFMK. Radiation‐induced decline in the total antioxidant capacity of plasma was significantly reversed in AFMK pretreated mice. Moreover, AFMK showed a very high level of in vitro hydroxyl radical scavenging potential which was measured by an electron spin resonance (ESR) study of the 2‐hydroxy‐5,5‐dimethyl‐1‐pyrrolineN‐oxide (DMPO‐OH) adduct. IC 50 values resulting from ESR analysis was 338.08 n m . The present study indicate that AFMK is a potent antioxidant in both in vivo and in vitro systems.