Tropisetron attenuates D-galactose-induced heart aging in male mice: activation of sirtuin1

This study pursued to evaluate the tropisetron effects in attenuating D-galactose induced heart aging in mice. The study aimed to ascertain whether tropisetron affects apoptotic processes, mitochondrial oxidative stress, or inflammatory variables in cardiac tissue, presumably through the modulation of the SIRT1 signaling pathway or sirtuin 1. Aging was induced via administration of D-galactose (200 mg/kg, s.c.). Then, mice were treated with tropisetron (1, 3, and 5 mg/kg/day, i.p.). After 8 weeks, the key indicators of oxidative mitochondrial dysfunction, oxidative stress, pro-inflammatory cytokines, interleukin-6, tumor necrosis factor-alpha, and nitric oxide concentrations were evaluated. Additionally, the gene expressions of apoptotic regulators Bax and Bcl2, as well as SIRT1, were assessed using real-time PCR. Histological alterations and serum lactate dehydrogenase levels were also assessed. Tropisetron alleviated mitochondrial oxidative stress and inflammatory mediators while decreasing immune cell infiltration into cardiac tissue generated by D-galactose. The simultaneous injection of tropisetron effectively inhibited D-galactose-induced apoptosis by modulating the Bax/Bcl2 ratio and activating the SIRT1 pathway. The administration of tropisetron resulted in reduced serum lactate dehydrogenase levels compared to the group treated just with D-galactose. Moreover, tropisetron successfully reinstated mitochondrial activity and diminished D-galactose-induced aberrant nitric oxide generation. The research concludes that tropisetron may provide protection against cardiac aging by activating multiple mechanisms associated with the SIRT1 pathway.