Open AccessEffects of specific interleukin‐1β‐converting enzyme inhibitor on ischemic acute renal failure in murine models 1
Author(s) -
LIU Huafeng,
LIANG Dong,
WANG Liming,
ZHOU Nan,
YAO Cuiwei,
HONG Tao,
TANG Deshen,
CHEN Xiaowen
Publication year - 2005
Publication title -
acta pharmacologica sinica
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.514
H-Index - 90
eISSN - 1745-7254
pISSN - 1671-4083
DOI - 10.1111/j.1745-7254.2005.00200.x
Subject(s) - blood urea nitrogen , kidney , renal function , creatinine , interleukin , nephrology , messenger rna , real time polymerase chain reaction , tumor necrosis factor alpha , medicine , endocrinology , andrology , cytokine , chemistry , biochemistry , gene
Aim: To study the effect of selective interleukin‐1 β‐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‐α (IFN‐α) 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‐γ 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‐γ 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‐γ mRNA transcription.