Combined Administration of Metformin and Propionate Reduces the Degree of Oxidative/Nitrosative Damage of Hypothalamic Neurons in Rat Model of Type 2 Diabetes Mellitus.

IF 4.3 2区医学 Q1 NEUROSCIENCES Molecular Neurobiology Pub Date : 2025-04-01 Epub Date: 2024-10-24 DOI:10.1007/s12035-024-04529-2

Larysa Natrus, Yuliia Klys, Yuliia Osadchuk, Moritz Anft, Timm Westhoff, Nina Babel

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Abstract

Many complications associated with type 2 diabetes mellitus (T2DM) are closely linked with the generation of reactive species or free radicals leading to oxidative/nitrosative stress. The aim of this study was to investigate the effect of combined administration of metformin with propionate on the degree of oxidative/nitrosative damage in the brain of rats with an experimental model of T2DM. Male Wistar rats were divided into control (healthy rats); rats with T2DM and no further therapy; rats with T2DM that received: metformin, propionate, propionate + metformin. Ventromedial hypothalamus samples were analyzed by transmission electron microscopy, gas-liquid chromatography, Western blotting, RT-PCR and electron paramagnetic resonance. Combined treatment resulted in normalization of the neuronal NOS levels and reduction of mRNA level of induced nitric oxide synthase (NOS) and superoxide radicals compared to untreated T2DM rats. A decrease was also observed in the level of 8-oxyguanine with normalization of fatty acids distribution. The combined treatment partially mitigated ultrastructural alterations resulting from oxidative/nitrosative damage in neurons' mitochondria in T2DM. Thus, we demonstrated a positive effect of the combined use of metformin and propionate on all indicators of oxidative/nitrosative stress in T2DM.

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联合服用二甲双胍和丙酸盐可降低 2 型糖尿病大鼠下丘脑神经元的氧化/亚硝基损伤程度

许多与 2 型糖尿病（T2DM）相关的并发症都与导致氧化/亚硝基应激的活性物质或自由基的产生密切相关。本研究旨在探讨二甲双胍与丙酸盐联合用药对 T2DM 实验模型大鼠大脑氧化/亚硝基损伤程度的影响。雄性 Wistar 大鼠分为：对照组（健康大鼠）；T2DM 大鼠（未接受进一步治疗）；T2DM 大鼠（接受二甲双胍、丙酸盐、丙酸盐 + 二甲双胍治疗）。透射电子显微镜、气液相色谱、Western 印迹、RT-PCR 和电子顺磁共振分析了下丘脑中下部的样本。与未经治疗的 T2DM 大鼠相比，联合治疗可使神经元 NOS 水平恢复正常，并降低诱导一氧化氮合酶（NOS）和超氧自由基的 mRNA 水平。此外，还观察到 8-氧鸟嘌呤水平下降，脂肪酸分布趋于正常。联合治疗部分缓解了 T2DM 大鼠神经元线粒体氧化/亚硝基损伤导致的超微结构改变。因此，我们证明了联合使用二甲双胍和丙酸盐对 T2DM 中所有氧化/亚硝基应激指标的积极影响。

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来源期刊

Molecular Neurobiology 医学-神经科学

CiteScore

9.00

自引率

2.00%

发文量

480

审稿时长

1 months

期刊介绍： Molecular Neurobiology is an exciting journal for neuroscientists needing to stay in close touch with progress at the forefront of molecular brain research today. It is an especially important periodical for graduate students and "postdocs," specifically designed to synthesize and critically assess research trends for all neuroscientists hoping to stay active at the cutting edge of this dramatically developing area. This journal has proven to be crucial in departmental libraries, serving as essential reading for every committed neuroscientist who is striving to keep abreast of all rapid developments in a forefront field. Most recent significant advances in experimental and clinical neuroscience have been occurring at the molecular level. Until now, there has been no journal devoted to looking closely at this fragmented literature in a critical, coherent fashion. Each submission is thoroughly analyzed by scientists and clinicians internationally renowned for their special competence in the areas treated.