Improvement in liver fibrosis, functionality and hemodynamics in CCl4-cirrhotic rats after injection of the Liver Growth Factor

Background/Aims: Most substances used in experimental models of cirrhosis a re chosen either as protectors of lipid peroxidation, as antifibrogenic age nts or as vitamins, among others. In this report, we analyze the improvemen t produced, in established cirrhosis (CCl4 plus phenobarbital) in rats: by intraperitoneal injection of Liver Growth Factor, a hepatic mitogen with ac tivity both in vivo and in vitro. Methods: Following confirmation of CCl4-induced cirrhosis, Liver Growth Fac tor (4.5 pg I,er ratx2 injections/week for 3 weeks) was administered; to on e group of rats (Cirr+LGF). The remaining rats (Cirr) received saline. The groups were compared in terms of serum enzymes, tissue damage, total liver collagen, collagenase activity, microsomal enzyme activities, splanchnic an d systemic hemodynamics and portosystemic shunting. Results: Treatment of rats presenting CCl4-induced cirrhosis with Liver Gro wth Factor decreased serum aminotransferase levels and increased levels of serum albumin and total protein. The Liver collagen content was lower in ra ts treated with Liver Growth Factor (2.96 vs 4.32 mg/g liver, p< 0.01). Mic roscopic studies revealed that the livers of rats receiving Liver Growth Fa ctor showed decreases in fibrosis, necrosis and inflammatory infiltration, as well as a recovery of architectural integrity. Liver function was improv ed after treatment with Liver Growth Factor, as indicated by the rate const ant for elimination of aminopyrine, which increased from 0.0063 to 0.0170 ( p<0.05). This increase was accompanied by a higher total amount of cytochro me P-450 as well as of certain P-450 isoenzymes, especially those that are hormone-dependent, such as P-450 3A. The improved liver histology and funct ion observed in Cirr+LGF rats was associated with decreases in portal press ure (14.4 vs 9.4 mmHg, p<0.01) and portosystemic shunting (55.8 vs 11.5%, p <0.01), as well as increases in mean arterial pressure and systemic vascula r resistance, and a reduction in ascites. Conclusions: Administration of the hepatic mitogen, Liver Growth Factor, to CCl4-cirrhotic rats decreased liver collagen and reorganized the hepatic e xtracellular matrix, resulting in an improvement in liver function, reduced portal pressure and amelioration of ascites.