Tropisetron attenuates pancreas apoptosis in the STZ-induced diabetic rats: involvement of SIRT1/NF-κB signaling

Background Diabetes mellitus (DM) is one of the most common diseases in the worldwide. Type 1 diabetes mellitus (T1DM) is characterized by insulin deficiency and beta cells apoptosis. Tropisetron as a 5-HT3 receptor antagonist has positive effects on the inflammation, apoptosis and glucose lowering. The aim of this study was to investigate the effect of tropisetron on beta-cells apoptosis and its possible pathways. Methods Animals were divided into five equal groups: the control, tropisetron, diabetes, tropisetron-DM and glibenclamide-DM (seven in each group). Tropisetron and glibenclamide were administrated for 2 weeks after type 1 diabetes induction. Real-time PCR, western blot analysis and TUNEL assay were performed. Results We found that tropisetron decreased blood glucose and increased insulin secretion. Protein expression of NF-kappa B was downregulated, while protein expression of SIRT1 upregulated after tropisetron treatment. Moreover, Bax/Bcl2 ratio decreased in tropisetron-DM group and finally, apoptosis improved in pancreas tissue. Conclusions It seems that tropisetron administration improves STZ-induced apoptosis and diabetes in the animals. This effect might be resulted from involvement in NF-kappa B/ SIRT1 pathway.