Mirshafa Atefeh, Shokrzadeh Mohammad, Amiri Fereshteh Talebpour, Mohammadi Hamidreza, Mohammadi Ebrahim, Zamani Ehsan, Alinia Mona, Shaki Fatemeh
Pharmaceutical Sciences Research Center, Hemoglobinopathy Institute, Mazandaran University of Medical Sciences, Sari, Iran.
Department of Toxicology and Pharmacology, Faculty of Pharmacy, Mazandaran University of Medical Sciences, Sari, Iran.
Naunyn Schmiedebergs Arch Pharmacol. 2024 Dec 20. doi: 10.1007/s00210-024-03711-6.
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.
本研究旨在评估托烷司琼对减轻D-半乳糖诱导的小鼠心脏衰老的作用。该研究旨在确定托烷司琼是否会影响心脏组织中的凋亡过程、线粒体氧化应激或炎症变量，推测其可能是通过调节SIRT1信号通路或沉默调节蛋白1来实现的。通过皮下注射D-半乳糖（200 mg/kg）诱导衰老。然后，对小鼠进行托烷司琼治疗（1、3和5 mg/kg/天，腹腔注射）。8周后，评估线粒体氧化功能障碍、氧化应激、促炎细胞因子、白细胞介素-6、肿瘤坏死因子-α和一氧化氮浓度的关键指标。此外，使用实时PCR评估凋亡调节因子Bax和Bcl2以及SIRT1的基因表达。还评估了组织学改变和血清乳酸脱氢酶水平。托烷司琼减轻了线粒体氧化应激和炎症介质，同时减少了D-半乳糖诱导的免疫细胞向心脏组织的浸润。同时注射托烷司琼通过调节Bax/Bcl2比值和激活SIRT1通路有效抑制了D-半乳糖诱导的细胞凋亡。与仅用D-半乳糖治疗的组相比，托烷司琼给药导致血清乳酸脱氢酶水平降低。此外，托烷司琼成功恢复了线粒体活性并减少了D-半乳糖诱导的异常一氧化氮生成。该研究得出结论，托烷司琼可能通过激活与SIRT1通路相关的多种机制来提供对心脏衰老的保护。
