Journal
ACTA PHARMACOLOGICA SINICA
Volume 26, Issue 11, Pages 1345-1351Publisher
BLACKWELL PUBLISHING
DOI: 10.1111/j.1745-7254.2005.00200.x
Keywords
kidney failure; ischemia; caspase-1; interleukin-1 beta-converting enzyme inhibitor; interleukin-1; interleukin-18; interferon type II
Ask authors/readers for more resources
Aim: To study the effect of selective interleukin-1 beta-converting enzyme (ICE, caspase-1) inhibitor on ischemic acute renal failure (ARF). Methods: Mouse models of ischemic ARF were treated with the specific ICE inhibitor AC-YVAD-CMK. A renal function assay and renal morphological studies were employed to estimate the renal protective effect of AC-YVAD-CMK. The survival rate of mouse models was also analyzed by a time series test. Furthermore, renal ICE activity, mature interleukin-18 (IL-18) protein expression and interferon-gamma (IFN-gamma) mRNA expression were also detected by fluorescent enzyme-linked immunosorbent assay (ELISA), ELISA, and semi-quantitative reverse transcription-polymerase chain reaction, respectively. Results: The levels of blood urea nitrogen (BUN) and serum creatinine (Scr) increased remarkably in the model controls compared with the sham-operated groups (P < 0.01). Typical renal tubular necrosis was found in the model controls. Renal ICE activity, mature IL-18 protein expression, and IFN-gamma mRNA expression were also increased significantly in the model controls compared with the sham-operated groups. The levels of BUN and Scr in the AC-YVAD-CMK therapy group were decreased significantly compared with the untreated model controls (P < 0.01). Renal tubulointerstitial lesion was also attenuated significantly (P < 0.05). AC-YVAD-CMK therapy alleviated the clinical features of ARF, and increased the survival rate (P < 0.01). Furthermore, AC-YVAD-CMK therapy also decreased ICE activity, mature IL-18 protein expression, and IFN-gamma mRNA expression in renal tissue (P < 0.05). Conclusion: The selective ICE inhibitor AC-YVAD-CMK can effectively protect the kidney from acute ischemic lesions. This protective effect is associated with decreased renal ICE activity and suppressed IL-18 maturation and IFN-gamma mRNA transcription.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available