Calcium Channel Blockers as Hepatoprotective agents in Paracetamol and Alcohol-induced Hepatotoxicity Models (Preventive Method) in Rats

Abstract

>Objective: To study the hepatoprotective activity of 3 Ca++ channel blockers namely felodipine (FEL), lercanidipine (LER), and isradipine (ISR) with three selected doses i.e; 1/4th TD, 1/2nd TD, and TD in paracetamol (PCM) and alcohol (ALC)-induced hepatotoxicity in rats both at preventing and curative aspects. Further, it was also reported that PCM and ALC producing hepatotoxicity by facilitating accumulation of excess Ca++ in hepatocyte. Ca++ channel blockers block the entry of Ca++ into the cells. Hence the present study is planned to evaluate the hepatoprotective activity of Ca++ channel blockers in the above-mentioned models. Materials and Methods: In rats, the hepatoprotective activity of Ca++ channel blockers is evaluated in PCM (2 g/Kg) and ALC (3.76 g/Kg) induced hepatotoxic models. Thiopental-induced sleeping time (TST), physical parameters like liver weight and liver volume, and biochemical parameters like alanine aminotransferase (ALT), aspartate aminotransferase (AST), serum alkaline phosphatase (ALP), serum direct bilirubin (BILD), serum total bilirubin (BILT), serum albumin (ALB), and serum total proteins (PRO), were estimated by Erba chem. Standard reference SIL produced significant hepatoprotective activity. Results: All three drugs significantly reduced liver weight to 6.07, 4.87, 5.51, 4.28, 6.10, and 5.02 g, respectively. Three drugs produced a significant reduction in liver volume noted as 6.03, 4.83, 5.45, 4.23, 6.05, and 4.96 mL, respectively, in paracetamol-induced hepatotoxicity. All three drugs significantly reduced liver weight, as 6.42, 5.65, 6.66, 6.34, 5.30, and 5.85 g, respectively. A significant reduction in liver volume was noted at 6.35, 5.53, 6.23, 5.18, and 5.80 mL, respectively, in alcohol-induced hepatotoxicity. Conclusion: Ca++ channel blockers too at three different doses at preventive and curative aspects produced a significant hepatoprotective activity in PCM and ALC-induced hepatotoxic models..