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Ex Vivo Investigation of Bexarotene and Nicotinamide Function as a Protectıve Agent on Rat Synaptosomes Treated with Aβ(1-42)

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Abstract

In this study, we were aimed to investigate the neuroprotective effects of bexarotene and nicotinamide in synaptosomes incubated with amyloid-beta (Aβ). Our study consists of 2 parts, in vivo and in vitro. In the in vivo section, twenty-four Wistar albino male rats were divided into 4 groups (control, dimethyl sulfoxide (DMSO), nicotinamide and bexarotene) with six animals in each group. DMSO(1%), nicotinamide(100 mg/kg) and bexarotene(0.1 mg/kg) were administered intraperitoneally to animals in the experimental groups for seven days. In the in vitro part of our study, three different isolation methods were used to obtain the synaptosomes from the brain tissue. Total antioxidant capacity(TAS), total oxidant capacity(TOS), cleaved caspase 3(CASP3), cytochrome c(Cyt c), sirtuin 1(SIRT1), peroxisome proliferator-activated receptor gamma(PPARγ) and poly(ADP-ribose) polymerase-1(PARP-1) levels in the synaptosomes incubated with a concentration of 10 µM Aβ(1-42) were measured by enzyme-linked immunosorbent assay method. Biochemical analysis and histopathological examinations in serum and brain samples showed that DMSO, nicotinamide and bexarotene treatments did not cause any damage to the rat brain tissue. We found that in vitro Aβ(1-42) administration decreased TAS, SIRT1 and PPARγ levels in synaptosomes while increasing TOS, CASP3, Cyt c, and PARP1 levels. Nicotinamide treatment suppressed oxidative stress and apoptosis by supporting antioxidant capacity and increased PPARγ through SIRT1 activation, causing PARP1 to decrease. On the other hand, bexarotene caused a moderate increase in SIRT1 levels with PPARγ activation. Consequently, we found that nicotinamide can be more effective than bexarotene in AD pathogenesis by regulating mitochondrial functions in synaptosomes.

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Funding

This study was supported by Eskişehir Osmangazi University Scientific Research Commission with grant number 201811D21.

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  1. Department of Medical Biochemistry, Faculty of Medicine, Duzce University, Duzce, Turkey

    Ceyhan Hacioglu

  2. Department of Medical Biochemistry, Faculty of Medicine, Eskisehir Osmangazi University, Eskisehir, Turkey

    Fatih Kar & Gungor Kanbak

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Hacioglu, C., Kar, F. & Kanbak, G. Ex Vivo Investigation of Bexarotene and Nicotinamide Function as a Protectıve Agent on Rat Synaptosomes Treated with Aβ(1-42). Neurochem Res 46, 804–818 (2021). https://doi.org/10.1007/s11064-020-03216-7

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