Scavenging reactive oxygen species using tempol in the acute phase of renal ischemia/reperfusion and its effects on kidney oxygenation and nitric oxide levels

Abstract

Background: Renal ischemia/reperfusion (I/R) injury is commonly seen in kidney transplantation and affects the allograft survival rates. We aimed to test our hypothesis that scavenging reactive oxygen species (ROS) with tempol would protect renal oxygenation and nitric oxide (NO) levels in the acute phase of renal I/R.

Methods: Rats were randomly divided: (1) no I/R, no tempol; (2) no I/R, but with tempol; (3) I/R without tempol; and (4) I/R with tempol. I/R was induced by 30-min clamping of the renal artery. Tempol (200 μmol/kg/h/i.v) was administered 15 min prior to I/R.

Results: I/R without tempol led to a significant decrease in renal oxygen delivery and microvascular oxygenation. Tempol, however, protected renal oxygenation after I/R. At R90, the creatinine clearance rate was lower in the I/R-subjected group that did not receive tempol compared to that in the other groups. I/R injury without tempol treatment led to a significant increase in tissue malondialdehyde levels and a significant decrease in tissue NO levels. Tempol administration before I/R could prevent oxidative stress and altered tissue NO levels.

Conclusions: This underscores that unbalance between oxygen, NO, and ROS forms an important component of the pathogenesis of I/R-induced AKI and should therefore be taken into account when designing a prevention/treatment strategy for renal I/R injury in transplantation.

Fig. 1

Renal oxygenation, oxidative stress, and nitric oxide (NO) levels at the end of the protocol. a Microvascular oxygen tensions (μpO₂) in the renal cortex; b Microvascular oxygen tensions (μpO₂) in the renal medulla; c renal tissue malondialdehyde (MDA) levels normalized to the tissue protein content; and d tissue NO levels normalized to the tissue protein content. *p < 0.05 vs all other groups; ^C p < 0.05 vs the CTRL group; ^T p < 0.05 vs the TMPL group