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Tropisetron attenuates D-galactose-induced heart aging in male mice: activation of sirtuin1
Atefeh Mirshafa1,2,3, Mohammad Shokrzadeh1,2, Fereshteh Talebpour Amiri4
1Pharmaceutical Sciences Research Center, Hemoglobinopathy Institute, Mazandaran University of Medical Sciences, Sari, Iran.
Abstract:
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-α, 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.
Insights
Tropisetron mitigates D-galactose-induced heart aging in mice by reducing oxidative stress, inflammation, and apoptosis. This cardioprotection is linked to activating the SIRT1 pathway, offering potential therapeutic benefits for cardiac aging.
Area of Science:
- Cardiovascular Biology
- Aging Research
- Pharmacology
Background:
- D-galactose administration is a common model to induce aging phenotypes, including cardiac dysfunction.
- Cardiac aging is characterized by increased oxidative stress, inflammation, and apoptosis.
- Sirtuin 1 (SIRT1) plays a crucial role in cellular protection and aging processes.
Purpose of the Study:
- To investigate the protective effects of tropisetron against D-galactose-induced heart aging in mice.
- To determine if tropisetron modulates apoptosis, mitochondrial oxidative stress, and inflammation in cardiac tissue.
- To explore the potential involvement of the SIRT1 signaling pathway in tropisetron's cardioprotective effects.
Main Methods:
- Mice were subjected to D-galactose administration to induce aging.
- Mice received varying doses of tropisetron.
- Evaluated markers included oxidative stress, inflammatory cytokines (IL-6, TNF-α), apoptosis regulators (Bax, Bcl2), SIRT1 expression, mitochondrial function, and serum lactate dehydrogenase.
Main Results:
- Tropisetron treatment alleviated mitochondrial oxidative stress and reduced inflammatory mediators in cardiac tissue.
- Tropisetron inhibited D-galactose-induced apoptosis by modulating the Bax/Bcl2 ratio and activating the SIRT1 pathway.
- Tropisetron administration decreased serum lactate dehydrogenase levels and improved mitochondrial activity.
Conclusions:
- Tropisetron demonstrates significant cardioprotective effects against D-galactose-induced heart aging.
- The protective mechanisms involve the activation of the SIRT1 pathway, reduction of oxidative stress, and anti-apoptotic effects.
- Tropisetron holds potential as a therapeutic agent for mitigating cardiac aging.
