4.7 Article

Oxidative damages in the DNA, lipids, and proteins of rats exposed to isofluranes and alcohols

Journal

TOXICOLOGY
Volume 220, Issue 2-3, Pages 169-178

Publisher

ELSEVIER IRELAND LTD
DOI: 10.1016/j.tox.2005.12.010

Keywords

alcohol; bone marrow; brain; comet assay; DNA damage; isoflurane; lipid peroxidation; liver; lung; lymphocytes; malondialdehyde; plasma; protein oxidation; single strand DNA breakage; spleen

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DNA damage, lipid peroxidation and protein oxidation were evaluated in rats exposed to a 1% isoflurane atmosphere with or without alcohol administration (administrated by gastric intubation at 4g/kg body weight as a 50% solution). Single cell gel electrophoresis assays were performed in order to evaluate DNA damage occurring in the lymphocytes, spleen, bone marrow, brain, livers and lung of rats exposed to 1% isoflurane for 30 or 60 min with/without ethanol. Levels of malondialdehydes (MDA), a metabolite of lipid peroxidation, were determined in plasma and tissues. Carbonyl contents were also analyzed to determine levels of protein oxidation in plasma and tissues. Levels of DNA damage in lymphocytes, bone marrow, and the organ tissues of rats exposed to isoflurane were found to increase time dependently, and alcohol increased DNA damage. Lipid peroxidation and protein oxidation results showed patterns that differed from those of DNA damage. Levels of MDA in plasma, bone marrow, spleen, and the livers of rats exposed to isoflurane with/without ethanol were found to be time dependently increased, but this was not observed in the brain or lung. However, protein oxidation levels were significantly increased in the plasma, brains, and lungs of rats exposed to isoflurane, and exposure to isoflurane and alcohol, significantly increased these levels in plasma and brain. The present study demonstrates that isoflurane exposure results in significant DNA damage in rat lymphocytes, bone marrow, spleen, brain, livers, and lung. Moreover, alcohol was found to be as a strong inducer of DNA damage, lipid peroxidation and protein oxidation. However, no evidence in association between DNA damage, lipid peroxidation and protein oxidation was found. Regarding the effects of isoflurane and alcohol on oxidative damages, single strand DNA damages may be a useful biomarkers and blood cells and plasma appear to be more sensitive targets to oxidative damage than other tissues. (c) 2005 Elsevier Ireland Ltd. All rights reserved.

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