Opioid receptors blockade modulates apoptosis in a rat model of cirrhotic cardiomyopathy

Abstract

Background: Cirrhosis is a common consequence of chronic liver inflammation is known to be associated with various manifestation of cardiovascular dysfunction, which has been introduced as a cirrhotic cardiomyopathy. Some possible pathogenic mechanisms has been reported and still more details should be explored.
Aim: The present study is the first study to explore the contribution of endogenous opioids in the apoptosis process in a rat model of cirrhotic cardiomyopathy.
Materials and Methods: Cirrhosis was induced in rats by bile duct ligation (BDL) and resection. Cardiomyopathy was confirmed using trichrome staining for fibrosis. Naltrexone, an opioid antagonist was administered for 29(1) days. Apoptosis was detected using terminal transferase deoxyuridine triphosphate nick end labeling assay with some modification. Statistical evaluation of data was performed using analysis of variance test. P < 0.05 was considered to be statistically significant.
Results: Left ventricular (LV) wall thickness was significantly (P < 0.001) lower in the BDL group than the sham group, either receiving naltrexone or saline. No significant difference was seen in LV wall thickness or LV end diastolic diameter in BDL group receiving either saline or naltrexone. The apoptosis density of cardiac specimens of sham operated and BDL rats were dramatically different from each other. The cardiac specimens of BDL rats contained multiple apoptotic cells. In saline treated samples (BDL‑saline vs. sham‑saline), apoptosis density was significantly increased in BDL‑saline group (P < 0.001). Cardiomyocyte apoptosis was significantly decreased in the BDL‑naltrexone group compared to BDL‑saline group (P < 0.001). There was no significant change in apoptosis density in sham groups receiving either naltrexone or saline. 
Conclusion: Apoptosis occurs during cirrhotic cardiomyopathy and endogenous opioid receptors blockade using naltrexone decreases its amount, but cardiac function may not be improved.

Keywords: Apoptosis, Cirrhotic cardiomyopathy, Naltrexone, Opioids