Abstract <p>Numerous heart-related problems are associated with livercirrhosis. This study aimed to evaluate the potential cardioprotectivebenefits of vitamin D₃ (Vit D) in cholestasis-inducedliver cirrhosis and the potential underlying interaction betweenvitamin D₃ and insulin-like growth factor-1(IGF-1). Thirty-two male Wistar rats weighing 180–220 g were allocatedinto four groups: sham control, vitamin D₃ (5000IU/kg, gavage, daily for 4 weeks), cirrhotic (Bile duct ligation(BDL)), and cirrhotic treated with vitamin D₃ (BDL,Vit D, 5000 IU/kg, gavage, daily for four weeks). Chronic biliarycirrhosis was elicited experimentally by common bile duct ligation.At the end of the experimental duration, blood pressure was measured,then the animals were anesthetized and an electrocardiogram wasrecorded. Serum bilirubin, IGF-1 and its binding proteins (II andIII), and NO were measured. In addition, cardiac and liver tissueswere evaluated biochemically for NO and IGF-1, and histopathologically.Vit D supplementation partially improved cirrhotic-induced cardiomyopathyand improved measured cardiovascular parameters. Moreover, it decreasedthe cirrhotic-induced excess collagen in the heart, together withdecreased expression of TNF-α, caspase-3, and vascular endothelialgrowth factor (VEGF). In addition, changes in serum and cardiactissue NO and IGF-1 levels in the cholestasis group were improvedupon Vit D supplementation. It can be concluded that Vit D supplementationwas associated with improvement of this cardiac dysfunction. VitD cardioprotective effects can be attributed to lowering the levelof nitric oxide. Furthermore, it decreases proinflammatory markerslike TNF-α and VEGF, and also decreases the expression of caspasein the cardiac tissue so acts as an anti-apoptotic agent. Thereis a possible indirect action of the stimulatory effect of Vit Don the hepatocytes, especially on IGF-1, which has well-known cardioprotectiveeffects.</p>