THE CYTOTOXIC EFFECT OF NICOTINE ON THE LIVER AND ITS MODULATION OF THE HEPATOXICITY INDUCED BY CARBON-TETRACHLORIDE IN RATS

Objective: To examine the hypothesis that nicotine is toxic to the liv er and potentiates the hepatotoxic effects of CCl4. Design: An animal model was used in which rats were given nicotine in concentrations sim ilar to those observed in habitual cigarette smokers. Results: Nicotin e given in drinking water (54 or 108 mumol/l) for 10 days significantl y reduced the growth of non-pregnant rats; the effects on pregnant ani mals were not significant. Nicotine (108 mumol/1) significantly increa sed the hepatic non-protein sulphydryl (SH) levels in both non-pregnan t and pregnant rats. However, the same solution did not affect foetal SH concentrations. CCl4 treatment (6 g/kg s.c.) also increased SH leve ls in the adults animals. Combined nicotine and CCl4 treatment did not further increase these levels in the liver. In non-pregnant rats, the alkaloid produced a biphasic effect on hepatic malondialdehyde (MDA) levels. Nicotine also significantly increased the severity of hepatic necrosis. However, nicotine failed to produce significant changes in e ither MDA levels or hepatic histology in pregnant animals. The MDA lev el in foetal livers was also unaffected. CCl4 markedly increased the h epatic MDA content in both pregnant and non-pregnant rats but histolog ical changes were only observed in non-pregnant animals. Conclusions: These results indicate that nicotine, as well as CCl4, given in concen trations similar to those observed in smokers produced liver damage as indicated by increased MDA levels and focal necrosis. Nicotine, howev er, did not aggravate the lipid peroxidation induced by CCl4 but furth er increased the pathological changes in the liver. Pregnant rats and their foetuses seemed to be resistant to the hepatotoxicity of nicotin e and CCl4.