The role of <i>SIRT1/PGC1-α</i> signaling pathway in high-dose vitamin D-Induced cardiotoxicity

IntroductionVitamin D overdose, often stemming from excessive supplementation rather than dietary intake. It has been associated with various conditions such as cardiovascular disorders. This study aimed to investigate the effects of vitamin D toxicity on cardiac tissue.MethodsSixteen Wistar rats (250 ± 50 g) were randomly divided into two groups: the control group and the high-dose vitamin D group (40,000 IU/kg). Vitamin D was administered via gavage for 8 weeks. The expression of sirtuin 1 (<i>SIRT1</i>), the peroxisome proliferator-activated receptor gamma co-activator 1-alpha (<i>PGC1-α</i>), B-cell lymphoma 2 (<i>Bcl-2</i>), and Bcl-2-associated X protein (<i>Bax</i>) genes in cardiac tissue was evaluated. Blood samples were analysed for lactate dehydrogenase (LDH) levels. Moreover, oxidative stress markers, including malondialdehyde (MDA) and superoxide dismutase (SOD), were measured in tissue samples. Histopathological evaluations were also conducted.ResultsThe expression of <i>SIRT1, PGC1-α, Bcl-2,</i> and the SOD levels were significantly decreased in the vitamin D-treated group. In addition, the values indicated a significant increase in the expression of Bax along with LDH and MDA levels in the vitamin D-treated group compared to the control group.DiscussionLong-term administration of high-dose vitamin D significantly increased oxidative stress and apoptosis in cardiac tissue, likely mediated by the <i>SIRT1/PGC1-α</i> pathway.Graphical abstractThe illustration of the suggested mechanism underlying high-dose vitamin D-induced cardiotoxicity.