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Protective effect of pregabalin on the brain tissue of diabetic rats

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Abstract

Purpose

Diabetes mellitus (DM) is a metabolic disorder characterized by insulin deficiency or insulin resistance. Pregabalin (PGB) is an antiepileptic drug with proven efficacy in the treatment of epilepsy, generalized anxiety disorder, and neuropathic pain. In this study, we aimed to investigate the protective effects of PGB in brain tissue of rats with streptozotocin (STZ)-induced experimental diabetes.

Materials and methods

Twenty-eight Wistar albino male rats were randomly divided into four groups with seven rats each: (I) Control group, (II) PGB (50 mg/kg PBG), (III) DM, and (IV) DM + PGB (50 mg/kg/day PGB per orally for 8 weeks). Diabetes was induced with an intraperitoneal (i.p.) STZ injection (Sigma Chemical Co Louis Missour, USA) at a dose of 180 mg/kg. STZ was dissolved in 0.1 M phosphate-citrate tampon (pH 4.5). Paraffin sections were examined using histological and immunohistochemical analyses. To detect oxidative damage biochemically, malondialdehyde (MDA), the end product of lipid peroxidation; superoxide dismutase (SOD), catalase (CAT), glutathione (GSH) and glutathione peroxidase (GPx) which are antioxidant enzymes, levels were studied. In addition, bax, caspase-3 enzyme activities and TUNEL assay were studied to evaluate the apoptosis status.

Results

In the DM group, MDA concentrations were significantly higher and GPx and SOD activities were significantly lower compared to the control group. MDA concentrations were significantly lower and SOD activity was significantly higher in the DM + PGB group than in the DM group. The GPx activity in the DM group decreased significantly compared to the control group. In immunohistochemical examinations (Bax, Caspase-3 and TUNEL), the apoptosis rate was significantly lower in the in DM + PGB group than in the DM group.

Conclusion

Pregabalin may prevent harmful effects of oxidative damage by decreasing the MDA levels and increasing the SOD levels. In addition, it was thought that PGB may have antiapoptotic properties due to decreased bax and caspase-3 immunoreactivity and TUNEL positivity in PGB groups. Based on these findings, we think that PGB may be effective in reducing the risk of brain damage associated with DM.

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Acknowledgements

We would like to thank Firat University Experimental Research Center for their contributions. This study was supported by a grant from Firat University.

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Authors and Affiliations

  1. Department of Neurology, Firat University School of Medicine, Elazig, Turkey

    Caner F. Demir

  2. Department of Neurology, Çukurova State Hospital, Adana, Turkey

    Metin Balduz

  3. Department of Neurology, Malatya Training Research Hospital, Malatya, Turkey

    İrem Taşcı

  4. Department of Histology, Firat University School of Medicine, Elazig, Turkey

    Tuncay Kuloğlu

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  1. Caner F. Demir
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  2. Metin Balduz
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  4. Tuncay Kuloğlu
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All autors confirm that this work is original and has not been published elsewhere nor is it currently under consideration for publication elsewhere.

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Correspondence to İrem Taşcı.

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Demir, C.F., Balduz, M., Taşcı, İ. et al. Protective effect of pregabalin on the brain tissue of diabetic rats. Diabetol Int 12, 207–216 (2021). https://doi.org/10.1007/s13340-020-00476-0

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