The effect of retinoic acid receptor agonist acitretin on the production of bile and concentrations of some serum components in ovariectomized rats

Abstract

Acitretin is an oral retinoid that is approved for the treatment of psoriasis and in the chemoprevention of nonmelanoma skin cancer. The metabolism of acitretin occurs in the liver and may affect other metabolic processes in the liver, such as metabolism of bilirubin, bile acids, and lipids. These processes may be also affected by physiologic loss of estrogens in postmenopausal women. Therefore, the aim of this study was to examine the effect of acitretin on the secretion and composition of bile and the turnover of cholesterol in a model of estrogen deficiency in ovariectomized rats. The study was carried out on female Wistar rats divided into three groups: sham-operated control, ovariectomized control, and ovariectomized rats receiving acitretin. The studied group was administered acitretin (Neotigason capsules 25 mg, Roche; 7.1 mg/kg body weight per 24 h) for 28 days. Bile fractions and blood were collected for determinations of concentration of bile acids, total cholesterol, calcium ions, chloride ions, and direct bilirubin. In addition, low-density lipoprotein (LDL) cholesterol and high-density lipoprotein (HDL) cholesterol were assayed. It was found that ovariectomy produced alterations in the process of secretion of bile and its principal components: cholesterol, bile acids, chloride ions, and bilirubin. The administration of acitretin decreased the secretion of bile and bile cholesterol, as well as serum levels of total, LDL, and HDL cholesterol, and moreover increased the proportion of bile acids to total cholesterol. Acitretin may influence the hepatic metabolism of bile, bile acids, and lipids. This action is associated with a decrease in factors influencing the lithogenicity of bile, with reductions in the serum levels of total, LDL, and HDL cholesterol.