Resveratrol and 1,25-dihydroxyvitamin D co-administration protects the heart against d-galactose-induced aging in rats: evaluation of serum and cardiac levels of klotho

The current study investigates the cooperative cardioprotective effect of calcitriol (active form of vitamin D) combined with resveratrol in a rat model of d-galactose (d.gal)-induced aging. Male Wistar rats received resveratrol (d.gal + Res), calcitriol (d.gal + Cal), or a combination of them (d.gal + Res + Cal). Intact animals served as control (Ctl). Blood pressure (BP) was recorded by cannulation of the left carotid artery. Fibrosis and cell size were assessed by Masson’s trichrome and hematoxylin–eosin staining, respectively. Cardiac and serum level of antiaging protein, klotho, was measured by ELISA assay method. Gene expression was evaluated by real-time RT-PCR. Biochemical tests were performed according to the standardized method. In d.gal + Res + Cal group, BP, heart weight-to-body weight ratio, and cardiomyocytes size decreased significantly compared with d-gal group. The cardiac transcription levels of catalase and superoxide dismutase 1 and 2 were upregulated in d.gal + Res + Cal compared to the d.gal group (P < 0.001, P < 0.05, P < 0.05, respectively). Increased level of malondialdehyde was observed in d.gal group (P < 0.01 vs. Ctl) which was normalized partially in d.gal + Res + Cal group (P < 0.05). Catalase and superoxide dismutase activity also increased in d.gal + Res + Cal group (P < 0.01 vs. d.gal). Cardiac Klotho, as the antiaging protein, remained unchanged at mRNA and protein levels among the experimental groups. The serum level of Klotho did not change significantly in d.gal group; however, in d.gal + Res + Cal group, serum klotho concentration was increased (P < 0.05 vs. d.gal). It could be concluded that co-administration of resveratrol and vitamin D protects the heart against aging-induced damage by the modulation of hemodynamic parameters and antioxidant status of the heart. Furthermore, increased serum level of klotho could be a novel mechanism for antiaging effects of resveratrol and vitamin D.