COMPARATIVE EFFECT OF SIL YMARIN AND ANGIOTENSIN CONVERTING ENZYME (ACE) INHIBITOR ON BIOCHEMICAL AND MORPHOLOGICAL ALTERATIONS OF REGENERATING LIVER

Abstract

Liver diseases are becoming more and more common and often reqUIre surgical resection. Liver, the vital body organ has the remarkable capacity to regenerate after partial hepatectomy (PHx) or toxic insult. However, fibrotic liver shows ,.impaired regeneration. Therefore there is need for such drugs that can enhance and improve regeneration of fibrotic liver after PHx. In current study a comparison was made to evaluate the efficacy of the two drugs i.e. silymarin and angiotensin converting enzyme (ACE) inhibitor on the morphological and biochemical parameters of regenerating fibrotic liver. Female Sprague -Dawley rats were made fibrotic by the administration of carbon tetrachloride (CCI4) dissolved in olive oil (1 :7) at the dose of 1.5ml/kg i.p for seven weeks while the vehicle group received 1.5mllkg i.p olive oil for the same duration. Then the animals received saline (lml), ACE-inhibitor (2. 5 mg/kg) and silymarin (70mg/kg) orally for one week before 55% PHx. 24hours after surgery the rats were dissected. The result showed that liver regeneration rate (LRR) of fibrotic animals and even that of drug treated ones was significantly less than vehicle. It was observed that both ACE inhibitor and silymarin treatment did not improve LRR significantly as compared to fibrotic control. Relative liver weight (RL W) of different groups showed no significant difference. Biochemical parameters like alanine aminotransferase (ALT), aspartate aminotransferase (AST) of vehicle were significantly low than all other groups having fibrotic rats. Bilirubin level, however, was significantly less in ACE inhibitor treated rats as compared to vehicle. A comparison of the liver enzymes of fibrotic animals after PHx showed that their level was significantly improved in ACE-Inhibitor group as compared to that of both fibrotic control and silymarin receiving rats. No significant difference in hepatic cell plate width (HCPW) of untreated fibrotic and normal livers after the surgery was observed. In drug treated groups silymarin showed no significant variation from both vehicle and fibrotic control, however, ACE inhibitor given rats had significantly less HPCW than all other groups. Sinusoidal width (SW) of vehicle was significantly more than fibrotic control and silymarin treated rats however, this difference was not observed in the case of ACE inhibitor group. ACE inhibitor treatment resulted in significantly more SW than both fibrotic control and silymarin group. Both drug treated and non-treated fibrotic regenerating rat livers had significantly more necrotic and apoptotic nuclei as compared to vehicle. ACE inhibitor treatment had significantly reduced the number of such nuclei in regenerating fibrotic livers after PHx. These results suggest that ACE-Inhibitor (2.Smg/kg) can improve the biochemical parameters of regenerating fibrotic livers more effectively than the silymarin (70mg/kg) after PHx. However, as far as the histological parameters are concemed neither drug proved to be effectively improving all the histological markers of liver regeneration. ACE inhibitor improves certain histological parameters more effectively than silymarin while certain others are effectively improved by silymarin.