BALANCE BETWEEN OXIDATIVE DAMAGE AND PROLIFERATIVE POTENTIAL IN AN EXPERIMENTAL RAT MODEL OF CCL4-INDUCED CIRRHOSIS - PROTECTIVE ROLE OF ADENOSINE ADMINISTRATION
R. Hernandezmunoz et al., BALANCE BETWEEN OXIDATIVE DAMAGE AND PROLIFERATIVE POTENTIAL IN AN EXPERIMENTAL RAT MODEL OF CCL4-INDUCED CIRRHOSIS - PROTECTIVE ROLE OF ADENOSINE ADMINISTRATION, Hepatology, 26(5), 1997, pp. 1100-1110
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.