ToxSci Advance Access originally published online on March 10, 2004
Toxicological Sciences 2004 82(1):228-236; doi:10.1093/toxsci/kfh103
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Toxicological Sciences vol. 82 no. 1 © Society of Toxicology 2004; all rights reserved.
Effects of Lead Exposure on the Expression of Phospholipid Hydroperoxidase Glutathione Peroxidase mRNA in the Rat Brain
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* Department of Neurology, Asan Medical Center, University of Ulsan, Seoul, 138–736 Republic of Korea; Department of Preventive Medicine, College of Medicine and Institute for Environmental Health, Medical Science Research Center, Korea University, Seoul, 136–701 Republic of Korea; Department of Veterinary Medicine, College of Veterinary Medicine, Chungbuk National University, Cheongju, 361–763, Republic of Korea
Received August 18, 2003; accepted February 4, 2004
Oxidative damage associated with lead in the brain has been proposed as a possible mechanism of lead toxicity. Of the many antioxidant enzymes, phospholipid hydroperoxidase glutathione peroxidase (PHGPx) is known to protect cells from lipid peroxide–mediated damage by catalyzing lipid peroxide reduction. In this study, the effects of lead on the activity and expression of PHGPx mRNA were investigated in the brains of rats exposed to lead for 8 weeks. Male Sprague-Dawley rats (3 week old, n = 40) were randomly divided into four groups of 10 and treated with four different concentrations of lead in drinking water: a low dose (0.1% lead acetate), a medium dose (0.3% lead acetate), and a high dose (1.0% lead acetate), and a control group (0% lead acetate). We compared the four groups in terms of body and brain weight, lead concentrations in the brain and blood, and the activities of superoxide dismutase (SOD), gluthatione peroxidase (GPx), and PHGPx mRNA in the brain. Phospholipid hydroperoxidase glutathione peroxidase was found to have a dominant role in lead exposure. We also performed in situ hybridization of PHGPx mRNA in the brain to identity PHGPx mRNA active sites. We found that the level of PHGPx mRNA in brain increased in the medium- and low-dose groups, but decreased in the high-dose group versus the non-lead-treated control group. These results suggest that lead exposure increases the expression of PHGPx mRNA in the low- and medium-dose groups without inducing structural changes, and that the reduced expression of PHGPx mRNA in the high-dose group was associated with structural damage. An In situ hybridization study showed that PHGPx mRNA in the brain is expressed mainly in the white matter of the cerebral hemisphere and in the Purkinje cells of the cerebellar hemispheres; these sites are known to be the vulnerable to lead toxicity.
Key Words: brain; gluthatione peroxidase; lead; oxidative damage; phospholipid hydroperoxidase; glutathione peroxidase; superoxide dismutase.