Expression of Testosterone-Dependent Enzyme, Carbonic Anhydrase III, and Oxidative Stress in Experimental Alcoholic Liver Disease

We studied the sequential immunohistochemicalappearance of androgen-dependent carbonic anhydrase (CAIII) during the development of ethanol-induced liverinjury using liver samples from castrated andnoncastrated male micropigs. In castrated micropigs, thebaseline expression of CA III was either low or absent,while distinct positive immunoreactions were found inzone 3 hepatocytes at 5 and 12 months after the initiation of the ethanol diet. The CA IIIenzyme and protein adducts of lipid peroxidation-derivedaldehydic products, malondialdehyde and4-hydroxynonenal, appeared together in the perivenousregion, suggesting that the enzyme functions in anoxidative environment. The positive staining became moreabundant and widespread during the progression ofalcoholic liver disease. After 12 months, CA III was significantly more abundant in both theethanol-fed noncastrated and castrated micropigs than inthe control animals (P < 0.001, P < 0.05,respectively). CA III content was strikingly high in the ethanol-fed noncastrated animals, consistentwith a potential role of androgens in the regulation ofethanol-induced CA III expression. The strongly positiveCA III immunoreactions in the ethanol-fed noncastrated micropigs were associated with scant evidenceof aldehydic protein adducts and minimal histopathology.Thus, enhanced expression of CA III during ethanolconsumption may also account in part for gender differences in the susceptibility foralcohol-induced liver injury.