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ToxSci Advance Access published online on November 9, 2005
Toxicological Sciences, doi:10.1093/toxsci/kfj041
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© The Author 2005. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org
Received September 25, 2005
Accepted November 3, 2005

Systems Toxicology

Smokeless Tobacco Impairs the Antioxidant Defense in Liver, Lung and Kidney of Rats

Pramod Kumar Avti 1, Surender Kumar 1, Chander Mohan Pathak 1, Kim Vaiphei 2, and Krishan Lal Khanduja 1*

1 Department of Biophysics, Postgraduate Institute of Medical Education and Research, Chandigarh - 160012, India
2 Department of Histopathology, Postgraduate Institute of Medical Education and Research, Chandigarh - 160012, India

* To whom correspondence should be addressed.
Krishan Lal Khanduja, E-mail: klkhanduja{at}rediffmail.com


  Abstract

The present study was designed to evaluate the effects of long term use of aqueous extract of ‘gutkha’ (a form of smokeless tobacco) on the antioxidant defense status and histopathological changes in liver, lung and kidney of male Wistar rats. Animals were orally administered with aqueous extract of smokeless tobacco (AEST) at a low dose (96mg/kg b.wt/day) for 2 and 32 weeks, and at a high dose (960 mg/kg b.wt/day) for 2 weeks. High dose of AEST for 2 weeks decreased the hepatic glutathione (GSH), glutathione peroxidase (GPx) and increased lipid peroxidation by 17%, 19% and 20% respectively. Administration of AEST at low dose for 32 weeks significantly decreased (p<0.05) the antioxidant status in these organs. In liver, AEST decreased GSH levels and the activities of superoxide dismutase (SOD), catalase (CAT) and GPx by 34.6%, 29%, 17.1% and 17.4% respectively but increased lipid peroxidation by 64%. In kidney, GSH, SOD, CAT and GPx were decreased by 26.6%, 23%, 33% and 18% respectively, with an increase of lipid peroxidation by 65%. AEST decreased the lungs GSH, SOD, CAT and GPx, and increased the lipid peroxidation by 43%, 28.5%, 37%, 40% and 24% respectively. However, no change in the plasma levels of vitamins A, C and E were observed with AEST treatment. Histopathological findings suggest that administration of AEST at high dose for 2 weeks or at low dose for 32 weeks could cause mild to moderate inflammation in liver and lungs. In conclusion, decreased antioxidant defense system and long term inflammation caused by smokeless tobacco may be a risk factor for gutkha-induced pathogenesis.

Keywords: Antioxidant enzymes; inflammation; lipid peroxidation; oxidative stress; reduced glutathione; smokeless tobacco; vitamins.
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