Protective effects of SP600125 on renal ischemia-reperfusion injury in rats.

Abstract

BACKGROUND:

Ischemia/reperfusion injury (IRI) has a negative effect on renal allograft survival. Using a rat model of kidney IRI in this study, we investigated the overall effect of selective c-Jun N-terminal kinase (JNK) inhibitor SP600125 on renal IRI events.

METHODS:

All 45 Fisher rats were anesthetized and renal IRI model was established by 45 min clamp of bilateral renal pedicles and 24 h reperfusion. Vehicle solution or SP600125 solution was intraperitoneally injected 45 min before ischemia, respectively. Analysis of renal histology, function, reactive oxygen species (ROS) expression, JNK phosphorylation status, as well as intra-renal pro-inflammatory cytokines expression was evaluated in this study.

RESULTS:

After IRI, the levels of blood urea nitrogen, creatinine, tissue malondialdehyde, TNF-α, IL-1β, IL-6 were all elevated significantly, while superoxide dismutase, catalase activity were decreased. Histologic findings showed severe devastating lesions and increased rodent cell apoptosis; SP600125 effectively improved morphologic features, reversed above-mentioned parameters, and significantly attenuated c-Jun phosphorylation, as well as intra-renal pro-inflammatory cytokines expression compared with vehicle-treated group.

CONCLUSION:

These data demonstrate that inhibition of c-Jun with SP600125 is capable of attenuating renal IRI, which might be a novel therapy target.

• Authors: Yun-fei Xu, Min Liu, Bo Peng, Jian-ping Che, Hai-min Zhang, Yang Yan, Guang-chun Wang, Yi-chao Wu, Jun-hua Zheng
• Journal: The Journal of surgical research (J Surg Res) Vol. 169 Issue 1 Pg. e77-84 (Jul 2011) ISSN: 1095-8673 [Electronic] United States
• PMID: 21492872 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2011 Elsevier Inc. All rights reserved.

Chemical References

• Anthracenes
• Cytokines
• Enzyme Inhibitors
• Reactive Oxygen Species
• pyrazolanthrone
• MAP Kinase Kinase 4

Topics

• Animals
• Anthracenes (pharmacology, therapeutic use)
• Apoptosis (drug effects, physiology)
• Cytokines (metabolism)
• Enzyme Inhibitors (pharmacology, therapeutic use)
• Ischemia (physiopathology)
• Kidney (blood supply, pathology, physiopathology)
• MAP Kinase Kinase 4 (antagonists & inhibitors, drug effects, metabolism)
• Male
• Models, Animal
• Phosphorylation
• Rats
• Rats, Inbred F344
• Reactive Oxygen Species (metabolism)
• Regional Blood Flow (physiology)
• Reperfusion Injury (metabolism, physiopathology, prevention & control)
• Treatment Outcome