Effects of KF-14363 on Liver Fibrosis in Rats with Chronic Liver Injury Induced by Carbon Tetrachloride

抄録

The present study examined the effects of (1-[(2-thiazolin-2-yl) amino]-acetyl-4-(1, 3-dithiol-2-ylidene)-2, 3, 4, 5-tetrahydro-1H-1-benzazepin-3, 5-dione hydrochloride (KF-14363) on liver fibrosis in rats with chronic liver injury induced by carbon tetrachloride (CCl₄). Liver injury in male rats was induced by repeated administration of CCl₄ at 0.5 ml/kg twice a week. The progression of liver fibrosis was checked in the 4th, 6th, 8th and 10th weeks using the relative amount of hepatic 4-hydroxy proline (4-hyp) to total proteine as an index of hepatic collagen. The relative amount of hepatic 4-hyp in these rats exceeded significantly that in rats not administered CCl₄ by the 4th week. This progressed in proportion to the duration of CCl₄ administration. In groups concurrently administered KF-14363 at 30 and 100 mg/kg/d from the 5th or 8th week of the CCl₄ administration, the relative amount of hepatic 4-hyp was found to be lower in the 10th week than at the start of the KF-14363 administration. The inhibition of liver fibrosis was also observed histopathologically. The concurrently co-administration with CCl₄ or KF-14363 at 30 and 100 mg/kg for 2 or 5 weeks inhibited the increases in serum transaminases and alkaline phosphatase induced by CCl₄. The results show that KF-14363 inhibits liver fibrosis in a dose dependent fashion in rats with progressive liver injury.