Rosuvastatin pretreatment suppresses distant organ injury following unilateral renal ischemia-reperfusion in hypertensive Dahl salt-sensitive rats.

Abstract

Ischaemia-reperfusion (I/R) induces distant organ injury (DOI) via inflammation and oxidative stress. Statins have anti-inflammatory and anti-oxidant effects independent of their cholesterol-lowering properties. To clarify whether statins could suppress DOI, we investigated the effect of rosuvastatin (RO) on the contralateral kidney following unilateral renal I/R. Dahl salt-sensitive rats (6 weeks old) were randomly divided into four groups: sham, sham with RO, I/R, and I/R with RO. All rats were fed a high-salt (8%) diet for 6 weeks. RO (10 mg/kg per day) was pre-administered by supplementation to the drinking water for 2 weeks before I/R. The rats then underwent unilateral renal I/R (ischemia for 45 min). Three days after I/R, laboratory data, histological changes and protein expression levels of the contralateral kidney were assessed. I/R significantly elevated serum creatinine and malondialdehyde levels and induced a significantly higher glomerular sclerosis index and tubular dilation area of the contralateral kidney, with about 2-fold infiltration of ED-1-positive cells. In the I/R group, protein expression of superoxide dismutase (SOD) of the contralateral kidney was reduced to about 50% of the sham group. RO-pretreatment significantly suppressed all of these changes following I/R. RO-pretreatment diminished contralateral kidney injury with the suppression of ED-1-positive cell infiltration and SOD reduction after I/R. RO appears to have a protective effect on DOI by its anti-inflammatory and anti-oxidant effects.