Introduction: 

Acute renal failure is a leading cause of death at the intensive care unit and develops frequently due to ischemic acute tubular necrosis (ATN). Reactive oxygen species (ROS), generated by oxidases during the reoxygenation phase have a major importance in extending the ischemic injury by inducing apoptotic processes. A year ago we reported that xanthine oxidase (XO) is upregulted in kidneys, but NADPH oxidases (NOXs) are not, after renal ischemia-reperfusion (IR) injury. Surprisingly, efficient silencing of these oxidases in resident renal cells with siRNA, in vivo, confered no protection to the kidney against IR injury. The aim of the present study was to investigate pharmacological oxidase-inhibitors on renal IR injury.

Methods: 

Before performing left renal ischemia (15 minutes), C57BL/6 mice were thirsted and injected iv. with NOX and XO inhibitors (10 mg per bwkg): apocynin and oxypurinol, respectively. Further 20 mg/kg BW was injected ip. after the intervention. After 24 hours of reperfusion kidney function was evaluated by blood urea retention (Reflotron).

Results: 

Blood urea levels raised significantly after IR injury (2.5 fold, p<0.001). Systemic apocynin treatment significantly reduced blood urea (1.9 fold, p<0.01) after IR injury compared to positive control group. However oxypurinol had no effect on blood urea levels after IR insult.

Discussion and conclusion: 

Although XO is upregulated in kidneys after IR injury, neither local, nor systemic inhibition of XO was beneficial. However, renal function improved after systemic inhibition of NOXs following IR injury, in spite of no change in NOXs expression during reperfusion in the kidneys. NOXs have a key role in immune cell function, therefore we suggest, that the major source of ROS is infiltrating neutrophils and not resident renal cells in IR injury.

Support: OTKA: K81972, NF69278; ETT: 011-07/2009