Protective effect of new nitrosothiols on the early inflammatory response to kidney ischemia/reperfusion and transplantation in rats.

Renal ischemia/reperfusion (I/R) is characterized by severe inflammatory damage. We assessed the effect of administrating recently developed nitrosothiol compounds acting as nitric oxide (NO) donors on the production of cytokines and other markers of acute inflammatory reaction in an experimental model of warm (I/R), and in a model of cold ischemia and transplant in rats. Warm ischemia was achieved by ligation of left renal pedicle for 60 min, followed by contralateral nephrectomy. NO-donors LA-803, LA-807, LA-810 were administered i.v. (1.8 μmol/kg) during 30 min before reperfusion. Cold ischemia was achieved by preservating the kidney for 24 h in Euro Collins and grafting it in consanguineous Fisher 344/Ico rats. LA-803 was administered in the preservation fluid and in the recipient rat. Reperfusion time was 4 h in warm ischemia and 3 h in cold ischemia + transplantation. Administration of LA-803, LA-807 and, in a lower proportion, LA-810 prevented from the enhanced production of tumor necrosis factor (...