Kumar Ashutosh, Kaundal Ravinder K, Iyer Seethalakshmi, Sharma Shyam S
Molecular Neuropharmacology Laboratory, Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research, Sector-67, S.A.S. Nagar, Punjab-160062, India.
Life Sci. 2007 Mar 6;80(13):1236-44. doi: 10.1016/j.lfs.2006.12.036. Epub 2007 Jan 20.
Oxidative stress has been implicated in pathophysiology of diabetic neuropathy. All the pathways responsible for development of diabetic neuropathy are linked to oxidative stress in one way or the other. In the present study, we have targeted oxidative stress in diabetic neuropathy using resveratrol, a potent antioxidant. Eight weeks streptozotocin-diabetic rats developed neuropathy which was evident from significant reduction in motor nerve conduction velocity (MNCV), nerve blood flow (NBF) and increased thermal hyperalgesia. The 2-week treatment with resveratrol (10 and 20 mg/kg, i.p.) started 6 weeks after diabetes induction significantly ameliorated the alterations in MNCV, NBF, and hyperalgesia. Resveratrol also attenuated enhanced levels of malondialdehyde (MDA), peroxynitrite and produced increase in catalase levels in diabetic rats. There was marked reduction in DNA fragmentation observed after resveratrol treatment in diabetic rats as evident from decrease in Terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) positive cells in sciatic nerve sections. Results of the present study suggest the potential of resveratrol in treatment of diabetic neuropathy and its protective effect may be mediated through reduction in oxidative stress and DNA fragmentation.
氧化应激与糖尿病神经病变的病理生理学有关。导致糖尿病神经病变发展的所有途径都以某种方式与氧化应激相关联。在本研究中,我们使用白藜芦醇(一种有效的抗氧化剂)针对糖尿病神经病变中的氧化应激进行了研究。链脲佐菌素诱导糖尿病8周的大鼠出现了神经病变,这从运动神经传导速度(MNCV)、神经血流量(NBF)的显著降低以及热痛觉过敏的增加中明显可见。在糖尿病诱导6周后开始用白藜芦醇(10和20mg/kg,腹腔注射)进行2周治疗,显著改善了MNCV、NBF和痛觉过敏的改变。白藜芦醇还降低了糖尿病大鼠丙二醛(MDA)、过氧亚硝酸盐的升高水平,并使过氧化氢酶水平升高。白藜芦醇治疗后糖尿病大鼠的DNA片段化明显减少,这从坐骨神经切片中末端脱氧核苷酸转移酶介导的dUTP缺口末端标记(TUNEL)阳性细胞的减少可以看出。本研究结果表明白藜芦醇在治疗糖尿病神经病变方面具有潜力,其保护作用可能通过降低氧化应激和DNA片段化来介导。