Cardiotrophin-1 administration protects from ischemia-reperfusion renal injury and inflammation

• Published in: Transplantation Vol. 96; no. 12; p. 1034
• Main Authors: Garcia-Cenador, María B, Lorenzo-Gomez, María F, Herrero-Payo, Julio J, Ruiz, Juan, Perez de Obanos, María P, Pascual, Julio, Lopez-Novoa, José M, Garcia-Criado, Francisco J
• Format: Journal Article
• Language: English
• Published: United States 27.12.2013
• Subjects: Animals; Apoptosis; Cytokines - administration & dosage; Inflammation; Interferon-gamma - metabolism; Interleukin-1beta - metabolism; Kidney - pathology; Kidney Transplantation - methods; Macrophages - metabolism; Male; Neutrophils - metabolism; NF-kappa B - metabolism; Nitric Oxide Synthase Type II - metabolism; Peroxidase - metabolism; Rats; Rats, Wistar; Reactive Oxygen Species; Reperfusion Injury - pathology; Reperfusion Injury - prevention & control; Superoxide Dismutase - metabolism; Superoxides - metabolism; Time Factors; Tumor Necrosis Factor-alpha - metabolism
• ISSN: 1534-6080
• DOI: 10.1097/TP.0b013e3182a74db4

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. 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. 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. 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.