Modification of lymphocyte DNA damage by antioxidant supplementation in LPS-treated rats

ABSTRACT

Oxidative stress and DNA damage have been implicated in the pathogenesis of many diseases such as chronic inflammation and sepsis. Oxidative DNA damage is an inevitable consequence of cellular metabolism, with a propensity for increased levels following toxic insult. Antioxidants could be a part of a protective strategy to minimize oxidative damage in such cases. The major goal of this study was to examine the ability of two antioxidants namely, alpha lipoic acid [ALA] and Antox [drug preparation] to protect brain from oxidative stress and modify lymphocyte DNA damage induced by lipopolysaccharid [LPS, endotoxin] Randomized seventy-five healthy adult male rats weighing 150-170 g were instructed to our experimental design. Lymphocyte DNA damage was measured using a single-cell gel electrophoresis [comet] assay. LPS injection resulted in a significant alteration on brain oxidative status observed as elevation in the level of malondialdehyde [MDA, index of lipid peroxidation], nitric oxide [NO] and reduction of reduced glutathione [GSH]. Also, the activities of antioxidant defense system, superoxide dismutase [SOD] and cataiase [CAT] were decreased significantly in rats' brain. Moreover, increase in the percentage damage of lymphocyte DNA concentration accompanied with higher tail length was observed following LPS administration. Antioxidants supplementation ameliorated brain oxidative stress by reducing levels of MDA and NO, restoring normal GSH content and normalizing the activities of antioxidant enzymes SOD and CAT. As well as the treated doses lowering the percentage of lymphocyte DNA damage and decreased tail length. In conclusion, antioxidants supplementation by ALA and Antox decreased brain oxidative stress markers and attenuated DNA damage