Exposure to ethanol and tobacco smoke in relation to level of PCNA antigen expression in pancreatic and hepatic rat cells

Pharmacol Rep. 2013;65(4):914-26. doi: 10.1016/s1734-1140(13)71073-9.

Abstract

Background: Previous results proved that simultaneous effect of tobacco smoke constituents and alcohol consumption may change toxicity of these substances and have a greater effect on hepatic and pancreatic disease and cancer risk. The aim of this study was to investigate hepatocyte and pancreatic cells regeneration after tobacco and/or ethanol treatment.

Methods: In the study, four groups of rats were used - alcohol non-addicted and addicted male and female rats. The animals from each group were exposed to tobacco smoke, to ethanol or tobacco smoke and ethanol. After the exposure, pancreas and liver were collected at two time-points--5 and 24 h. Biochemical methods were used to measure concentration of ethanol and cotinine in blood and plasma. Additionally, proliferating cell nuclear antigen labeling index (PCNA-LI), an S-phase marker was assessed by immunohistochemical staining and morphometric method.

Results: Our experimental results showed that the exposure of rats to tobacco smoke does not have influence on ethanol concentration in blood of non-addicted (male, female) and addicted (male and female) animals. The results also proved that alcohol addiction did not influence nicotine metabolism in all animals exposed to tobacco smoke. Morphological studies of tissues display significant damage in liver of addicted males, including fatty degradation, fibrosis and slight inflammatory infiltrate. Immunohistochemical studies revealed at first, significant increase of PCNA-LI and, thus, increased cell proliferation activity and damage in tissues were observed in hepatic and pancreatic cells of addicted males when compared with non-addicted males. Secondly, comparison between addicted males and addicted females revealed that PCNA-LI in females is significantly lower, both in hepatic and pancreatic tissues. And finally, animals exposed only to ethanol and to tobacco smoke plus ethanol were characterized by higher percentage of PCNA positive cells in relation to animals exposed only to tobacco smoke.

Conclusion: From the preliminary study one can conclude that the influence of ethanol and simultaneous influence of ethanol and tobacco smoke impairs liver and pancreatic functions to a greater degree than tobacco abuse.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alcoholism / blood
  • Alcoholism / metabolism
  • Alcoholism / pathology
  • Animals
  • Cell Proliferation / drug effects
  • Cotinine / blood
  • Ethanol / blood
  • Ethanol / toxicity*
  • Female
  • Hepatocytes / drug effects*
  • Hepatocytes / metabolism
  • Liver / drug effects*
  • Liver / pathology
  • Male
  • Nicotine / blood
  • Pancreas / drug effects*
  • Pancreas / metabolism
  • Pancreas / pathology
  • Proliferating Cell Nuclear Antigen / biosynthesis*
  • Rats
  • Sex Characteristics
  • Tobacco Smoke Pollution / adverse effects*

Substances

  • Proliferating Cell Nuclear Antigen
  • Tobacco Smoke Pollution
  • Ethanol
  • Nicotine
  • Cotinine