Remote preconditioning reduces oxidative stress, downregulates cyclo-oxygenase-2 expression and attenuates ischaemia-reperfusion-induced acute kidney injury.

Remote preconditioning (rPeC) is a phenomenon by which short-time intermittent ischaemia-reperfusion (I/R) of a remote organ during ischaemia protects other organs from I/R injury (IRI). The aim of the present study was to investigate the protective effect of rPeC on renal IRI in rats. Rats were subjected to right nephrectomy and randomized as into a sham group (no additional intervention), an I/R group (subjected to 45 min left renal pedicle occlusion) and an rPeC group (subjected to four cycles of 5 min I/R of the left femoral artery administered at the beginning of renal ischaemia). After 24 h, blood, urine and tissue samples were collected. Compared with the sham group, I/R resulted in renal dysfunction, as evidenced by significantly lower creatinine clearance (CCr; 0.52 ± 0.06 vs 0.11 ± 0.02 mL/min, respectively) and higher fractional excretion of sodium (FE(Na) ; 0.80 ± 0.07% vs 2.46 ± 0.20%, respectively). This was accompanied by decreased superoxide dismutase (SOD; 6.9 ± 1.7 vs 26.7 ± 2.7 U/g tissue) and catalase (CAT; 20.2 ± 8.8 vs 32.2 ± 8.7 K/g tissue) activity in the I/R group, as well as decreased levels of reduced glutathione (GSH; 21.7 ± 8.1 vs 81.2 ± 20.2 μmol/g tissue) and increased malondialdehyde levels (MDA; 1.2 to 0.1 vs 0.5 ± 0.2 μmol/100 mg), cyclo-oxygenase (COX)-2 expression and histological damage. In the rPeC group, renal histology and function were significantly improved (CCr 0.32 ± 0.02 mL/min; FE(Na) 1.33 ± 0.12%) compared with the I/R group. Furthermore, compared with the I/R group, the rPeC group exhibited increases in SOD and CAT activity (22.8 ± 3.8 U/g tissue and 21.7 ± 8.6 K/g tissue, respectively), increased GSH levels (74.0 ± 4.9) and decreased MDA levels (1.1 ± 0.3 μmol/100 mg) and COX-2 expression. In conclusion, rPeC appears to exert protective effects against renal IRI. This protection may be a consequence of reductions in lipid peroxidation, intensification of anti-oxidant systems and downregulation of COX-2 expression. A simple approach, rPeC may be a promising strategy for protection against IRI in clinical practice.
(© 2012 The Authors Clinical and Experimental Pharmacology and Physiology © 2012 Wiley Publishing Asia Pty Ltd.)