Cardiotrophin-1 administration prevents the renal toxicity of iodinated contrast media in rats
- Yaremi Quiros(1),
- Penelope D. Sánchez-González(1),
- Francisco J. López-Hernández(2)(3)(4),
- Ana I. Morales(2)(3) and
- José M. López-Novoa(2)(3)
+ Author Affiliations
- (1) Bio-inRen S.L., Salamanca, Spain.
- (2) Unidad de Fisiopatología Renal y Cardiovascular. Departamento de Fisiología y Farmacología, Universidad de Salamanca, Salamanca, Spain
- (3) Instituto de Investigación Biomédica de Salamanca (IBSAL), Salamanca, Spain
- (4) Instituto de Estudios de Ciencias de la Salud de Castilla y León (IESCYL)
- Corresponding author José Miguel López-Novoa Contact email: email@example.com University of Salamanca, Department of Physiology and Pharmacology, Edificio Departamental, Campus Miguel de Unamuno, Salamanca, Spain, 37007, +34 923294472 Fax: (+34) 923 294 669
- Received November 7, 2012.
Although generally reversible, contrast media toxicity often induces contrast-induced nephropathy (CIN), which is associated to longer hospitalization time, the need of dialysis, and higher incidence of later cardiovascular events and higher mortality. Preventive co-treatments have been assayed at the preclinical and clinical levels, but recent meta-analysis have not demonstrated a beneficial effect, which supports the search for new nephroprotective strategies. We have assessed if the administration of cardiotrophin-1 (CT-1), an endogenous cytokine with protective properties on the heart and liver, might mitigate CIN in rats. We have developed a model of CIN induced by the administration of the contrast medium gastrographin i.v. (3.7 mg/kg). in rats sensitized by previous administration of sub-nephrotoxic doses of gentamicin (50 mg/kg/day, i.p.) for 6 days. The severity of CIN was assessed by measurement of renal function, renal histological damage, urinary excretion of markers of tubular damage including NAG, KIM-1 and PAI-1, lipid peroxidation and renal apoptosis. Treatment with cardiotrophin-1 almost completely prevented the renal tissue damage as evidenced by almost total prevention of tubular desepithelization and tubular obstruction, reduced caspase activation and cell proliferation. Besides, CT-1 also prevented the increment in renal tissue levels of renal tissue injury markers NAG, KIM-1 and NGAL. Oxidative stress, a hallmark of contrast-induced nephropathy, was also prevented by CT-1. Administration of CT-1 also prevented the derangement in kidney function induced by CIN. Renal hemodynamics, also impaired by the contrast medium, were normal in rats co-treated with CT-1. Cardiotrophin-1 administration significantly prevents the alterations in renal function and structure observed in a rat model of CIN.
- Acute kidney injury
- contrast-induced nephropathy
- contrast nephrotoxicity