We have located links that may give you full text access.
Journal Article
Research Support, Non-U.S. Gov't
Salubrinal, an eIF2α dephosphorylation inhibitor, enhances cisplatin-induced oxidative stress and nephrotoxicity in a mouse model.
Free Radical Biology & Medicine 2011 August 2
Although cisplatin attacks various tumors with remarkable efficacy, its clinical usage has been limited by its side effects, particularly nephrotoxicity. Salubrinal, a selective eukaryotic translation initiation factor 2 subunit α (eIF2α) dephosphorylation inhibitor, has been found to protect cells from endoplasmic reticulum (ER)-stress-induced cytotoxicity. In this study, we hypothesized that salubrinal would protect against cisplatin-induced nephrotoxicity in a mouse model. Cisplatin treatment significantly increased serum blood urea nitrogen and creatinine levels, renal kidney injury marker (kim-1) mRNA expression, renal cell apoptosis, and renal histopathological changes in mice. Unexpectedly, administration of salubrinal significantly enhanced the cisplatin-induced nephrotoxicity in mice. Salubrinal by itself did not induce alterations in the function or histomorphology of mouse kidneys. Salubrinal significantly enhanced the phosphorylation of eIF2α, the protein expression of activating transcription factor 4 and CCAAT/enhancer binding protein homologous protein, and the cleavage of caspases 12, 9, and 3 in the kidneys of cisplatin-treated mice. Moreover, salubrinal enhanced the cisplatin-induced oxidative stress in the kidneys. The antioxidant N-acetylcysteine significantly reversed the increased renal lipid peroxidation, activated renal caspase cascade, and increased blood BUN and creatinine in cisplatin-alone- or cisplatin plus salubrinal-treated mice. These findings suggest that salubrinal aggravates cisplatin-induced nephrotoxicity through the enhancement of oxidative stress and ER stress-related cell apoptosis.
Full text links
Related Resources
Get seemless 1-tap access through your institution/university
For the best experience, use the Read mobile app
All material on this website is protected by copyright, Copyright © 1994-2024 by WebMD LLC.
This website also contains material copyrighted by 3rd parties.
By using this service, you agree to our terms of use and privacy policy.
Your Privacy Choices
You can now claim free CME credits for this literature searchClaim now
Get seemless 1-tap access through your institution/university
For the best experience, use the Read mobile app