<p>Cholestasis, a condition characterized by impaired bile flow, can lead to severe liver damage if left untreated. Current therapeutic options are limited, necessitating the development of novel treatment strategies. This study investigated the synergistic action of cilnidipine, a calcium channel blocker, and bexarotene, a retinoid X receptor (RXR) agonist, in mitigating cholestatic liver damage induced by alpha-naphthyl isothiocyanate (ANIT) in rats. The study aimed to elucidate the role of the farnesoid X receptor (FXR) signaling cascade in the protective effects of the combined treatment. Rats were divided into three groups: a negative control group, an ANIT-treated group, and a group pretreated with cilnidipine and bexarotene before ANIT administration. Biochemical markers of liver function, oxidative stress, and inflammation were assessed, along with histological examination of liver tissue. The expression of genes related to the FXR signaling pathway was also evaluated using quantitative polymerase chain reaction (qPCR). The results demonstrated that pretreatment with cilnidipine and bexarotene significantly attenuated ANIT-induced cholestatic liver damage, as evidenced by improved liver function markers, reduced oxidative stress and inflammation, and ameliorated histological changes. Furthermore, the combined treatment upregulated the expression of FXR and its target genes, suggesting that the protective effects may be mediated through the activation of the FXR signaling cascade. These findings highlight the potential of cilnidipine and bexarotene as a novel therapeutic approach for the management of cholestatic liver disorders and provide insights into the underlying molecular mechanisms involving the FXR signaling pathway.</p>