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

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.

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.

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.

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