Nicotinamide and Nicotinoyl-Gamma-Aminobutyric Acid as Neuroprotective Agents Against Type 1 Diabetes-Induced Nervous System Impairments in Rats.

Autor: Kuchmerovska T; Department of Vitamin and Coenzyme Biochemistry, Palladin Institute of Biochemistry, National Academy of Sciences of Ukraine, Kyiv, Ukraine. tkuchmerovska@gmail.com., Tykhonenko T; Department of Vitamin and Coenzyme Biochemistry, Palladin Institute of Biochemistry, National Academy of Sciences of Ukraine, Kyiv, Ukraine., Yanitska L; Department of Medical Biochemistry and Molecular Biology, Bogomolets National Medical University, Kyiv, Ukraine., Savosko S; Department of Histology and Embryology, Bogomolets National Medical University, Kyiv, Ukraine., Pryvrotska I; I. Horbachevsky Ternopil National Medical University, Ministry of Health of Ukraine, Ternopil, Ukraine.
Jazyk: angličtina
Zdroj: Neurochemical research [Neurochem Res] 2024 Nov 11; Vol. 50 (1), pp. 1. Date of Electronic Publication: 2024 Nov 11.
DOI: 10.1007/s11064-024-04257-y
Abstrakt: Diabetes is a multifunctional chronic disease that affects both the central and/or peripheral nervous systems. This study assessed whether nicotinamide (NAm) or conjugate of nicotinic acid with gamma-aminobutyric acid (N-GABA) could be potential neuroprotective agents against type 1 diabetes (T1D)-induced nervous system impairments in rats. After six weeks of T1D, induced by streptozotocin, nonlinear male Wistar rats were treated for two weeks with NAm (100 mg/kg, i. p.) or N-GABA (55 mg/kg, i. p.). Expression levels of myelin basic protein (MBP) were analyzed by immunoblotting. Polyol pathway parameters of the sciatic nerves were assessed spectrophotometrically, and their structure was examined histologically. NAm had no effect on blood glucose or body weight in T1D, while N-GABA reduced glucose by 1.5-fold. N-GABA also increased MBP expression by 1.48-fold, enhancing neuronal myelination, while NAm showed no such effect. Activation of the polyol pathway was observed in the T1D sciatic nerves. Both compounds decreased sorbitol content and aldose reductase activity, thereby alleviating changes similar to primary degeneration in the sciatic nerves and preventing peripheral neuropathy development. These results demonstrate that NAm and, more notably, N-GABA may exert neuroprotective effects against T1D-induced nervous system impairments by increasing MBP expression levels, improving myelination processes in the brain, inhibiting the polyol pathway, and partially restoring morphometric parameters in the sciatic nerves. This suggests their potential therapeutic efficacy as promising agents for the prevention of T1D-induced nervous system alterations.
Competing Interests: Declarations Ethical Approval All animal experiments were carried out in accordance with the Directive 2010/63/ EU and approved by the Animal Care and Use Committee of Palladin Institute of Biochemistry, NAS of Ukraine. Competing Interests The authors declare no competing interests.
(© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)
Databáze: MEDLINE
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