The effect of endogenous opioids on apoptosis of cardiomyocytes in a rat model of cirrhotic cardiomyopathy

Background:Cirrhosis is a common consequence of chronic liver inflammation is known to be associatedwith various manifestation of cardiovascular dysfunction which has been introduced as acirrhotic cardiomyopathy.Aim:To explore the contribution of endogenous opioids in the apoptosis process in a rat model ofcirrhotic cardiomyopathy.Material and Methods:Cirrhosis was induced in rats by bile duct ligation (BDL) and resection. Naltrexone, an opioidantagonist was administered for 4 weeks. Apoptosis was detected using TUNEL assay withsome modification. For molecular analysis, expression of BCL2, Caspase3, Fas and FasL wasexplored using real-time PCR.Results:Apoptosis density of cardiac specimens of sham operated and BDL rats were dramaticallydifferent from each other. In saline treated samples (BDL-saline vs sham-saline), apoptosisdensity was significantly increased in BDL-saline group (P <0.001). Cardiomyocyteapoptosis was significantly decreased in the BDL-naltrexone group compared to BDL-salinegroup (P<0.001). There was no significant change in apoptosis density in sham groupsreceiving either naltrexone or saline. BDL-saline group showed significant over-expressionof BCL2 and FAS and down regulation of caspase3 by a factor of 1.44(p<0.001) compared tosham-saline group, 1.3(p<0.001) compared to BDL-naltrexone group and 0.77(p<0.001)compared to sham-naltrexone group, respectively. No significant change was observed in theother 4 analysis for BCL2, caspase3 and FAS. The expression pattern of FASL revealed nostatistically significant changes in the study groups.Conclusion:Apoptosis occurs during cirrhotic cardiomyopathy through both intrinsic and extrinsicpathways activation and endogenous opioid receptors blockade using naltrexone decreases itsamount.