Effects of specific interleukin-1β-converting enzyme inhibitor on ischemic acute renal failure in murine models.
In: Acta Pharmacologica Sinica, Jg. 26 (2005-11-01), Heft 11, S. 1345-1351
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Zugriff:
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. [ABSTRACT FROM AUTHOR]
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Effects of specific interleukin-1β-converting enzyme inhibitor on ischemic acute renal failure in murine models.
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Autor/in / Beteiligte Person: | Liu, Hua-feng ; Liang, Dong ; Wang, Li-ming ; Zhou, Nan ; Yao, Cui-wei ; Hong, Tao ; Tang, De-shen ; Chen, Xiao-wen |
Zeitschrift: | Acta Pharmacologica Sinica, Jg. 26 (2005-11-01), Heft 11, S. 1345-1351 |
Veröffentlichung: | 2005 |
Medientyp: | academicJournal |
ISSN: | 1671-4083 (print) |
DOI: | 10.1111/j.1745-7254.2005.00200.x |
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