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. 1993 Nordic Pharmacological Society