Dexmedetomidine Pretreatment Attenuates Kidney Injury and Oxidative Stress during Orthotopic Autologous Liver Transplantation in Rats.
Xiaofang YuXinjin ChiShan WuYi JinHui YaoYiheng WangZheng-Yuan XiaJun CaiPublished in: Oxidative medicine and cellular longevity (2015)
This paper aims to explore whether pretreatment with dexmedetomidine (Dex) has antioxidative and renal protective effects during orthotopic autologous liver transplantation (OALT) and its impact on nuclear factor erythroid 2-related factor 2 (Nrf2) activation. Sprague-Dawley rats were randomized into groups that include sham-operated (group S), model (group M), low dose Dex (group D1), high dose Dex (group D2), atipamezole (a nonspecific α2 receptor blocker) + high dose Dex (group B1), ARC239 (a specific α2B/c receptor blocker) + high dose Dex (group B2), and BRL-44408 (a specific α2A receptor blocker) + high dose Dex (group B3). Then histopathologic examination of the kidneys and measurement of renal function, the renal Nrf2 protein expression, and oxidants and antioxidants were performed 8 hours after OALT. We found that pretreatment with Dex activated Nrf2 in glomerular cells and upregulated antioxidants but reduced oxidants (all P < 0.01, group D2 versus group M). Atipamezole and BRL-44408, but not ARC239, reversed these protective effects. In conclusion, pretreatment with Dex activates Nrf2 through α2A receptor, increases the antioxidant levels, and attenuates renal injury during OALT.
Keyphrases
- high dose
- oxidative stress
- low dose
- stem cell transplantation
- induced apoptosis
- nuclear factor
- dna damage
- toll like receptor
- ischemia reperfusion injury
- double blind
- randomized controlled trial
- acute kidney injury
- immune response
- signaling pathway
- diabetic rats
- clinical trial
- anti inflammatory
- cell death
- heat shock
- heat shock protein
- inflammatory response
- study protocol