Chronic effects of smokeless tobacco extract on rat liver histopathology and production of HSP-90.

Tobacco consumption is a worldwide problem. The recent increase in the consumption of the smokeless tobacco products (snuff and chewing tobacco) has stimulated interest into the carcinogenic effects of these forms of tobacco. The use of smokeless tobacco products has increased in popularity as the use of cigarettes has become less socially acceptable. For most individuals the use of tobacco is a chronic process. Therefore, the effects of an aqueous extract of smokeless tobacco (STE) in rats following low-dose exposure were examined. Female Sprague-Dawley rats were treated orally with 25 mg STE/kg every other day for 90 days. In order to obtain information regarding the cytotoxicity of STE, the ultrastructural changes occurring in livers of rats following administration of STE were examined under light and electron microscopy. Electron microscopy revealed that in the perisinusoidal spaces an accumulation of indistinct filamentous material occurred following 60 days of treatment, occupying most of the sinusoids. Moreover, the lipids were in a state of disintegration. Significant increases in 90 kDa protein expression were also observed due to chronic treatment with STE. Western blot analysis using a polyclonal mouse antibody against heat shock/stress protein 90 (HSP90) confirmed that the overexpressed proteins were heat shock/stress proteins (HSPs). The HSPs are believed to serve as adaptive or survival functions involving a rapid but transient reprogramming of cellular metabolic activity to protect cells from oxidative damage.