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.