Neuroprotective effect of naringin by modulation of endogenous biomarkers in streptozotocin induced painful diabetic neuropathy
Neuroprotective effect of naringin by modulation of endogenous biomarkers in streptozotocin induced painful diabetic neuropathy
复制标题
DOI：
10.1016/j.fitote.2012.01.010
复制
发表时间：
2012-06-01
期刊：
影响因子：
3.4
通讯作者：
Bodhankar, Subhash L.
中科院分区：
文献类型：
--
作者：
Kandhare, Amit D.;Raygude, Kiran S.;Bodhankar, Subhash L.
糖尿病是一种严重的使人衰弱的流行病，影响到发展中国家和发达国家的所有社会阶层。糖尿病性神经病变是糖尿病最常见的继发性并发症，其特点是神经传导速度减慢、疼痛加剧、感觉丧失和神经纤维变性。研究柚皮苷对链脲佐菌素（STZ）诱导的大鼠糖尿病神经性疼痛的神经保护作用。腹腔注射STZ后4周，机械触觉异常性痛、机械痛觉过敏、热痛觉过敏及运动神经传导速度均显著降低。内源性抗氧化剂如超氧化物歧化酶和膜结合无机磷酸酶的活性也显著降低。它不仅能引起神经细胞凋亡，还能提高脂质过氧化、亚硝酸盐和炎症介质（tnf - α）的水平。柚皮苷（40和80 mg/kg）慢性治疗4周后，损伤阈值、内源性抗氧化剂和膜结合无机磷酸酶水平的下降有明显的剂量依赖性。对神经细胞氧化亚硝化应激、炎症介质及细胞凋亡水平均有明显的剂量依赖性降低。本研究的重要发现是，在糖尿病大鼠中，柚皮苷-胰岛素联合用药不仅能减轻糖尿病病情，还能逆转神经性疼痛，而胰岛素或柚皮苷单独用药仅能改善高血糖，但部分逆转疼痛反应。因此，柚皮苷是一种潜在的具有抗氧化、抗凋亡和疾病修饰特性的黄酮，通过调节内源性生物标志物来抑制糖尿病引起的神经性疼痛。(C) 2012 Elsevier B.V.版权所有
Diabetes mellitus is a serious debilitating epidemic affecting all social strata in developing as well as developed countries. Diabetic neuropathy is most common of secondary complications associated with diabetes mellitus and is characterized by slowing of nerve conduction velocity, elevated pain, sensory loss and nerve fiber degeneration. The aim of the present investigation was to evaluate the neuroprotective effect of naringin against streptozotocin (STZ) induced diabetic neuropathic pain in laboratory rats. Four weeks after intraperitoneal injection of STZ resulted in significant decrease in mechano-tactile allodynia, mechanical hyperalgesia, thermal hyperalgesia and motor nerve conduction velocity. Activity of endogenous antioxidant like superoxide dismutase as well as membrane bound inorganic phosphate enzyme was also found to be significantly decreased. It not only caused neural cell apoptosis but also enhanced lipid peroxide, nitrite, and inflammatory mediators' (TNF-alpha) level. Chronic treatment with naringin (40 and 80 mg/kg) for 4 weeks significantly and dose dependently attenuated the decrease in level of nociceptive threshold, endogenous antioxidant and membrane bound inorganic phosphate enzyme. It also decreased the elevated levels of oxidative-nitrosative stress, inflammatory mediators as well as apoptosis in neural cells significantly and dose dependently. The important finding of the study is that, the naringin-insulin combination not only attenuated the diabetic condition but also reversed the neuropathic pain, whereas insulin or naringin alone only improved hyperglycemia but partially reversed the pain response in diabetic rats. Thus, naringin is a potential flavonone bearing antioxidant, antiapoptotic and disease modifying property acting via modulation of endogenous biomarker to inhibit diabetes induced neuropathic pain. (C) 2012 Elsevier B.V. All rights reserved.