Suppression of NF-魏B and NF-魏B regulated oxidative stress and neuroinflammation by BAY 11-7082 (I魏B phosphorylation inhibitor) in experimental diabetic neuropathy
- 作者：Ashutosh Kumar ; Geeta Negi ; Shyam S. Sharma ; sssharma@niper.ac.in
- 关键词：Diabetic neuropathy ; Oxidative stress ; Inflammation ; NF-魏B
- 刊名：Biochimie
- 出版年：2012
- 期刊代码：24_03009084
- 类别：bio
- 出版时间：May, 2012
- 卷：94
- 期：5
- 页码：1158-1165
- 文件大小：891 K
摘要
Inflammation is an emerging patho-mechanism of diabetes and its complications. NF-魏B pathway is one of the central machinery initiating and propagating inflammatory responses. The present study envisaged the involvement of NF-魏B inflammatory cascade in the pathophysiology of diabetic neuropathy using BAY 11-7082, an I魏B phosphorylation inhibitor. Streptozotocin was used to induce diabetes in Sprauge Dawley rats. BAY 11-7082 (1 & 3聽mg/kg) was administered to diabetic rats for 14 days starting from the end of six weeks post diabetic induction. Diabetic rats developed deficits in nerve functions and altered nociceptive parameters and also showed elevated expression of NF-魏B (p65), I魏B and p-I魏B along with increased levels of IL-6 & TNF-伪 and inducible enzymes (COX-2 and iNOS). Furthermore, there was an increase in oxidative stress and decrease in Nrf2/HO-1 expression. We observed that BAY 11-7082 alleviated abnormal sensory responses and deficits in nerve functions. BAY 11-7082 also ameliorated the increase in expression of NF-魏B, I魏B and p-I魏B. BAY 11-7082 curbed down the levels of IL-6, TNF-伪, COX-2 and iNOS in the sciatic nerve. Lowering of lipid peroxidation and improvement in GSH levels was also seen along with increased expression of Nrf2/HO-1. Thus it can be concluded that NF-魏B expression and downstream expression of proinflammatory mediators are prominent features of nerve damage leading to inflammation and oxidative stress and BAY 11-7082 was able to ameliorate experimental diabetic neuropathy by modulating neuroinflammation and improving antioxidant defence.