Changes in expression of the albumin, fibronectin and type I procollagen genes in CCl4-induced liver fibrosis: Effect of pyridoxol L,2-pyrrolidon-5 carboxylate

The protective activity of pyridoxol L,2-pyrrolidon-5 carboxylate (metadoxine) was investigated in a rat model of carbon tetrachloride (CCL₄)-induced hepatic fibrosis. After 6 weeks of CCl₄ treatment, the animals developed fibrosis and inflammation of the liver while those treated with CCl₄+metadoxine had less severe lesions (P <0.05). Since in liver fibroplasia there are quantitative changes of the extracellular matrix components and almost invariably a decrease in albumin synthesis, we have also investigated by Northern blot analysis the expression of the cellular fibronectin, pro-alpha2(I)collagen and albumin genes. There were striking increases in fibronectin and pro-alpha2(I)collagen mRNA contents in the livers of CCL₄-treated animals and these enhancements were less evident in the metadoxine-treated rats. In contrast, albumin mRNA levels, almost identical in control and metadoxine-treated rats, were lower in the CCl₄-treated animals. These data suggest that metadoxine might slow the development of CCl₄-mediated liver fibrosis.