BALANCE BETWEEN OXIDATIVE DAMAGE AND PROLIFERATIVE POTENTIAL IN AN EXPERIMENTAL RAT MODEL OF CCL4-INDUCED CIRRHOSIS - PROTECTIVE ROLE OF ADENOSINE ADMINISTRATION

Oxidative stress and its consequent lipid peroxidation (LP) exert harm ful effects, which have been currently involved in the generation of c arbon tetrachloride-induced cirrhosis. However, the recent report that ''physiological'' LP can be associated with liver regeneration (LR) m akes it necessary to discriminate between oxidative stress-induced and LR-associated LP, In rats rendered cirrhotic by continuous CCl4 admin istration for 4 weeks, moderate cell necrosis and fine fatty infiltrat ion were found. The histological abnormalities were accompanied by inc reased LP, mainly accounted for by the microsomal and cytosolic fracti ons and evidence of oxidative stress (decreased hepatic glutathione co ntent and changes in xanthine oxidase and pentose phosphate pathway ac tivities), After 8 weeks, a micronodular cirrhosis developed, but oxid ative stress was greatly attenuated, only persisting in the enhanced L P confined to microsomes. Simultaneous administration of adenosine, a reliable hepatoprotector that readily prevents the onset of liver fibr osis, was able to block the oxidative stress induced by the long-term CCL4 treatment but elicited a selective subcellular distribution of in creased LP, similar to that found during LR. The adenosine-induced cha nges in liver LP (mainly in the nuclear fraction) correlated with an i ncreased activity of thymidine kinase, Therefore, data suggest that ad enosine-mediated preservation of energy availability and mitochondrial function could participate in preventing the onset of oxidative stres s in cirrhotic rats, The latter could induce a successful liver recove ry, curtailing the sequence of events leading to fibrogenesis.