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AFMK, a melatonin metabolite, attenuates X-ray-induced oxidative damage to DNA, proteins and lipids in mice.
J Pineal Res. 2007 Apr; 42(4):386-93.JP

Abstract

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 nm. The present study indicate that AFMK is a potent antioxidant in both in vivo and in vitro systems.

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Authors+Show Affiliations

Manda K
National Institute of Radiological Science, Chiba, Japan.
Ueno M
No affiliation info available
Anzai K
No affiliation info available

MeSH

8-Hydroxy-2'-DeoxyguanosineAnimalsAntioxidantsCerebral CortexComet AssayDNADNA DamageDeoxyguanosineFree Radical ScavengersKynuramineLipid PeroxidationMaleMelatoninMiceMice, Inbred C57BLNerve Tissue ProteinsOxidation-ReductionOxidative StressX-Rays

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

17439555

Citation

Manda, Kailash, et al. "AFMK, a Melatonin Metabolite, Attenuates X-ray-induced Oxidative Damage to DNA, Proteins and Lipids in Mice." Journal of Pineal Research, vol. 42, no. 4, 2007, pp. 386-93.
Manda K, Ueno M, Anzai K. AFMK, a melatonin metabolite, attenuates X-ray-induced oxidative damage to DNA, proteins and lipids in mice. J Pineal Res. 2007;42(4):386-93.
Manda, K., Ueno, M., & Anzai, K. (2007). AFMK, a melatonin metabolite, attenuates X-ray-induced oxidative damage to DNA, proteins and lipids in mice. Journal of Pineal Research, 42(4), 386-93.
Manda K, Ueno M, Anzai K. AFMK, a Melatonin Metabolite, Attenuates X-ray-induced Oxidative Damage to DNA, Proteins and Lipids in Mice. J Pineal Res. 2007;42(4):386-93. PubMed PMID: 17439555.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - AFMK, a melatonin metabolite, attenuates X-ray-induced oxidative damage to DNA, proteins and lipids in mice. AU - Manda,Kailash, AU - Ueno,Megumi, AU - Anzai,Kazunori, PY - 2007/4/19/pubmed PY - 2007/5/23/medline PY - 2007/4/19/entrez SP - 386 EP - 93 JF - Journal of pineal research JO - J Pineal Res VL - 42 IS - 4 N2 - 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 nm. The present study indicate that AFMK is a potent antioxidant in both in vivo and in vitro systems. SN - 0742-3098 UR - https://www.unboundmedicine.com/medline/citation/17439555/AFMK_a_melatonin_metabolite_attenuates_X_ray_induced_oxidative_damage_to_DNA_proteins_and_lipids_in_mice_ L2 - https://doi.org/10.1111/j.1600-079X.2007.00432.x DB - PRIME DP - Unbound Medicine ER -