Cardiotrophin-1 Administration Protects from Ischemia-Reperfusion Renal Injury and Inflammation

BACKGROUND: Ischemia-reperfusion injury (IRI) remains a major problem in renal transplantation, and the inflammatory response to IRI exacerbates the resultant renal injury. We have investigated whether the systemic administration of cardiotrophin-1 (CT-1) is able to improve renal function and to decrease inflammatory responses in a rat model of renal IRI. METHODS: IRI was induced by renal pedicle clamping (60 min) followed by reperfusion and contralateral nephrectomy. CT-1 was injected through the penile vein 30 min before clamping release and its effects were compared with a saline-treated group at five different time points of reperfusion. RESULTS: Survival in the CT-1-treated group was higher than in the untreated group and prevented IRI-induced reduction in the glomerular filtration rate, as shown by blunted increases in creatinine and urea plasma levels and less severe decrease in creatinine clearance. These effects of CT-1 seem to be mediated by reduction in oxygen-radical production, increased superoxide dismutase expression, attenuation of neutrophil and macrophage infiltration, lower adhesion molecule expression, lower inflammation demonstrated by a decrease of plasma levels of proinflammatory cytokine secretion such as tumor necrosis factor-α, interleukin-1β and interferon-γ, lower inducible nitric oxide synthase expression and lower nuclear factor-κB activation, and reduced apoptosis. CONCLUSIONS: Therefore, these results suggest that CT-1 administration prevents IRI and it might be used as a therapeutic strategy to protect the kidney against IRI.