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

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Abstract

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 β-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-κB 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-κB/ SIRT1 pathway.

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Authors and Affiliations

  1. Nephrology and Kidney Transplant Research Center, Urmia University of Medical Sciences, Urmia, Iran

    Roya Naderi & Alireza Shirpoor

  2. Department of Physiology, Faculty of Medicine, Urmia University of Medical Sciences, Urmia, Iran

    Roya Naderi & Alireza Shirpoor

  3. Cellular and Molecular Research Center, Cellular and Molecular Medicine Institute, Urmia University of Medical Sciences, Urmia, Iran

    Mahrokh Samadi

  4. Neurophysiology Research Center, Urmia University of Medical Sciences, Urmia, Iran

    Bagher Pourheydar

  5. Department of Anatomical Sciences, Faculty of Medicine, Urmia University of Medical Sciences, Urmia, Iran

    Bagher Pourheydar

  6. Cellular and Molecular Research Center, Qom University of Medical Sciences, Qom, Iran

    Azam Moslehi

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  1. Roya Naderi
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Correspondence to Azam Moslehi.

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Naderi, R., Shirpoor, A., Samadi, M. et al. Tropisetron attenuates pancreas apoptosis in the STZ-induced diabetic rats: involvement of SIRT1/NF-κB signaling. Pharmacol. Rep 72, 1657–1665 (2020). https://doi.org/10.1007/s43440-020-00146-7

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  • DOI: https://doi.org/10.1007/s43440-020-00146-7

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