Investigation of the protective effects of dichloroacetic acid in a rat model of diabetic neuropathy.

IF 2.7 3区 医学 Q2 PHARMACOLOGY & PHARMACY BMC Pharmacology & Toxicology Pub Date : 2025-01-22 DOI:10.1186/s40360-025-00849-8
Murat Arı, Mumin Alper Erdogan, Oytun Erbaş
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Abstract

Background: Diabetic neuropathy (DN) is a heterogeneous condition characterized by complex pathophysiological changes affecting both autonomic and somatic components of the nervous system. Inflammation and oxidative stress are recognized contributors to the pathogenesis of DN. This study aims to evaluate the therapeutic potential of dichloroacetic acid (DCA) in alleviating DN symptoms, focusing on its anti-inflammatory and antioxidant properties.

Methods: Thirty-two adult male Sprague Dawley rats were divided into four groups: Control, Diabetic, and two DCA-treated groups receiving 5 mg/kg and 10 mg/kg of DCA, respectively. Diabetes was induced with streptozotocin (STZ) injections. Assessments included lipid peroxidation levels, plasma fibroblast growth factor-21 (FGF-21) and transforming growth factor-beta (TGF-β) levels, electrophysiological measurements, histological examination of the sciatic nerve, and motor function tests.

Results: Treatment with DCA significantly reduced malondialdehyde (MDA) levels, indicating decreased lipid peroxidation. Plasma TGF-β levels were also lower in the DCA-treated groups, suggesting diminished inflammation. Conversely, plasma FGF-21 levels were elevated. Electrophysiological assessments revealed enhanced compound muscle action potential (CMAP) amplitudes and reduced distal latencies in DCA-treated rats, indicative of improved nerve conduction. Histopathological examinations showed reduced perineural thickness in the sciatic nerves of DCA-treated rats, pointing to decreased fibrosis. Enhanced performance in motor function tests was observed in these rats, implying improved muscle strength and motor capacity.

Conclusions: The study demonstrates that DCA therapy significantly reduces oxidative stress and inflammation in a rat model of DN, thereby ameliorating neuropathic symptoms. These results support the potential of DCA as a promising therapeutic agent for DN treatment. Further research is warranted to explore its clinical applications and to provide more detailed insights.

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二氯乙酸对糖尿病神经病变大鼠模型保护作用的研究。
背景:糖尿病性神经病变(DN)是一种异质性疾病,其特征是影响神经系统自主神经和躯体神经成分的复杂病理生理变化。炎症和氧化应激是公认的DN发病机制的贡献者。本研究旨在评估二氯乙酸(DCA)在缓解DN症状方面的治疗潜力,重点关注其抗炎和抗氧化特性。方法:将32只成年雄性sd大鼠分为4组:对照组、糖尿病组和DCA治疗组,DCA剂量分别为5 mg/kg和10 mg/kg。采用链脲佐菌素(STZ)诱导糖尿病。评估包括脂质过氧化水平、血浆成纤维细胞生长因子-21 (FGF-21)和转化生长因子-β (TGF-β)水平、电生理测量、坐骨神经组织学检查和运动功能测试。结果:DCA治疗显著降低丙二醛(MDA)水平,表明脂质过氧化降低。dca处理组的血浆TGF-β水平也较低,表明炎症减轻。相反,血浆FGF-21水平升高。电生理评估显示,dca处理的大鼠复合肌肉动作电位(CMAP)振幅增强,远端潜伏期减少,表明神经传导改善。组织病理学检查显示dca处理大鼠坐骨神经周围神经厚度减少,表明纤维化减少。这些大鼠在运动功能测试中表现增强,这意味着肌肉力量和运动能力得到改善。结论:本研究表明,DCA治疗可显著降低DN大鼠模型的氧化应激和炎症,从而改善神经病变症状。这些结果支持DCA作为一种有前途的DN治疗药物的潜力。需要进一步的研究来探索其临床应用并提供更详细的见解。
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来源期刊
BMC Pharmacology & Toxicology
BMC Pharmacology & Toxicology PHARMACOLOGY & PHARMACYTOXICOLOGY&nb-TOXICOLOGY
CiteScore
4.80
自引率
0.00%
发文量
87
审稿时长
12 weeks
期刊介绍: BMC Pharmacology and Toxicology is an open access, peer-reviewed journal that considers articles on all aspects of chemically defined therapeutic and toxic agents. The journal welcomes submissions from all fields of experimental and clinical pharmacology including clinical trials and toxicology.
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