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Human & Experimental Toxicology
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The role of dopamine in manganese-induced oxidative injury in rat pheochromocytoma cells

K Seth

Industrial Toxicology Research Centre, Mahatma Gandhi Marg, Post Box 80, Lucknow-226 001, India

A K Agrawal

Industrial Toxicology Research Centre, Mahatma Gandhi Marg, Post Box 80, Lucknow-226 001, India; aka33{at}rediffmail.com

I Date

Department of Neurological Surgery, Okayama Medical School, Okayama, Japan

P K Seth

Industrial Toxicology Research Centre, Mahatma Gandhi Marg, Post Box 80, Lucknow-226 001, India

Reactive dopamine (DA) metabolites have been implicated in both Parkinson's disease and manganese (Mn) neurotoxicity. Rat PC12 and genetically modified PC12 (PC12M) cells capable of producing higher DA content, on exposure to MnCl2 (10¡ 6 M) for 72 hours, exhibited a significant decrease in glutathione content. Activity of antioxidant enzyme catalase was also inhibited following 24 and 72-hour MnCl2 exposure. MnCl2 caused a concentration dependent (10¡ 7 to 10¡3 M) loss in mitochondrial activity after 24 and 72 hours and an impaired DNA synthesis after 72 hours with changes being more marked in PC12M cells. The results indicate that the free-radical-mediated toxicity of Mn at cellular level involves down-regulation of anti oxidants in normal and DA-rich PC12 cells. PC12M cells appeared to be more sensitive than PC12 cells.

Key Words: catalase • dopamine • glutathione • Mn • PC12 cell line • SOD

Human & Experimental Toxicology, Vol. 21, No. 3, 165-170 (2002)
DOI: 10.1191/0960327102ht228oa
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