Background: Following our hypothesis that oxidative stress might play a primary role in renal ischemia/reperfusion injury (RIRI), we investigated if ethyl pyruvate (EPy) with potent antioxidant activity might prevent or alleviate RIRI induced in rats. Methods: Sprague-Dawley rats were randomly divided into four groups: (A) Sham, (B) renal ischemia/reperfusion (RIR), (C) RIR with EPy supplement (RIR+EPy), and (D) RIR with Mann supplement (RIR+Mann). Mannitol (Mann), a preoperative agent being clinically used, was tested for comparison with EPy. Rats were subjected to 40-min ischemia, followed by 24-h reperfusion. Either EPy or Mann was given to rats 30 min prior to ischemia and immediately before the reperfusion period. Results: The RIR and RIR+Mann groups showed palpable kidney injuries with the ~5-fold elevated blood urea nitrogen (BUN) and creatinine (Cr) levels, indicating renal dysfunction. However, the kidneys in the RIR+EPy group appeared merely normal (similar to the Sham’s) with the basal BUN/Cr levels, indicating normal renal function. No effects on histology, BUN or Cr were yet seen with Mann. Moreover, specific kidney injury markers were up-regulated and oxidative stress was also ~2.1-fold severer in the RIR group, whereas little changes in those markers and oxidative stress were seen with EPy supplement (RIR+EPy). Conclusions: Although oxidative stress feasibly plays a key role in RIRI, EPy with antioxidant activity is capable of protecting the kidneys from such an assault. Thus, EPy (not Mann) should be considered as an effective perioperative renoprotective agent that could be used clinically.
Upregulation of heme oxygenase 1 (HO-1) attenuates kidney damage, oxidative stress and inflammatory reaction during renal ischemia/reperfusion injury
