Possible role of cell redox state on collagen metabolism in carbon tetrachloride-induced cirrhosis as evidenced by adenosine administration to rats

Abstract

Marked changes in the redox state of liver cells in carbon tetrachloride (CCl 4)-induced cirrhosis after chronic treatment with the hepatotoxin (4−8 weeks) were observed. A shift of the redox state towards the reduced side is noticed in both compartments, cytosol and mitochondria. At 8 weeks of treatment an imbalance between these two compartments was evident. The alteration produced by the CCl 4 treatment in the cell redox state might be related to the mitochondrial damage elicited by the hepatotoxin. Adenosine treatment to CCl 4-poisoned rats was able to counteract the effect of the hepatotoxin on the redox equilibrium; hence, it could be linked to the beneficial action of the nucleoside in the maintenance of mitochondrial function. The changes in the hepatocyte redox state, induced by CCl 4 and/or adenosine, seem to modify collagen and nitrogen metabolism, indicating a linear correlation between the redox state and the collagen synthesis rate, whereas an inverse relationship was observed with collagenase activity. The possible role of the changes in cell redox state as signals for communication between parenchymal and mesenchymal liver cells is discussed. The results suggest an important correlation among mitochondrial function, cellular redox state, and regulation of collagen metabolism that could be relevant for the physio-pathology of this model of experimental cirrhosis.