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-alpha 2(I)collagen and albumin genes. There were striking increases in fibronectin and pro-alpha 2(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.
Arosio
B
B
Institute of Internal Medicine, University of Milano, Italy.
Santambrogio
D
D
Gagliano
N
N
Annoni
G
G
D000418:Albumins / Q000187:drug effects / Q000235:genetics*; D000818:Animals; D015152:Blotting, Northern; D002251:Carbon Tetrachloride; D004195:Disease Models, Animal; D004338:Drug Combinations; D005260:Female; D005353:Fibronectins / Q000187:drug effects / Q000235:genetics*; D005786:Gene Expression Regulation / Q000187:drug effects*; D008106:Liver Cirrhosis, Experimental / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology; D011347:Procollagen / Q000187:drug effects / Q000235:genetics*; D011736:Pyridoxine / Q000494:pharmacology*; D011761:Pyrrolidonecarboxylic Acid / Q000494:pharmacology*; D012313:RNA / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley
D000418:Albumins; D004338:Drug Combinations; D005353:Fibronectins; D011347:Procollagen; D012313:RNA; D002251:Carbon Tetrachloride; C037845:metadoxine; D011736:Pyridoxine; D011761:Pyrrolidonecarboxylic Acid