The effects of nicotine on microRNA-124 expression in the bile duct ligation- induced liver fibrosis in rats

Abstract

Background Smoking causes a variety of adverse effects on organs that have no direct contact with the smoke itself such as the liver. Nicotine as a main compound of smoking may exert its effects by changing the expression of microRNAs (miRNAs). This study was conducted to further investigate the molecular mechanisms of miRNA-dependent effects of nicotine in an animal model of liver fibrosis. Methods First, the bile duct ligation (BDL) approach was used in male Wistar rats to create a model of liver fibrosis. Then, the effects of nicotine administration on miRNA-124 expression, as well as fibrosis and inflammation-related genes were investigated using the quantitative Real-Time PCR method. The total bilirubin and liver enzymes activity levels were measured using the colorimetric assay. Also, the effects of nicotine on the process of liver fibrosis were investigated with histological studies. Results The development of liver fibrosis in BDL rats leads to a decrease in miRNA-124 expression. Also, a decrease in miRNA-124 expression has been seen in the groups administered nicotine. The decrease in the expression of miRNA-124 is accompanied by the increase in the expression of fibrotic and proinflammatory genes. Also, the significant increase in bilirubin and liver enzymes in fibrotic rats worsens with nicotine administration. The results of histological studies also confirm these results. Conclusion Considering that miRNA-124 is an anti-inflammatory miRNA, it can be concluded that the decrease in its expression due to nicotine exposure leads to an increase in inflammatory processes and subsequently to an increase in liver fibrosis.