title: Cardiotrophin-1 administration prevents the renal toxicity of iodinated contrast media in rats.
abstract: Although generally reversible, contrast media toxicity often induces contrast-induced nephropathy (CIN), which is associated with longer hospitalization time, the need for dialysis, and higher incidence of later cardiovascular events and higher mortality. Preventive cotreatments have been assayed at the preclinical and clinical levels, but recent meta-analysis has 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 iv (3.7mg/kg) in rats sensitized by previous administration of subnephrotoxic doses of gentamicin (50mg/kg/day, ip) for 6 days. The severity of CIN was assessed by the measurement of renal function; renal histological damage; urinary excretion of markers of tubular damage, including N-acetyl beta glucosaminidase (NAG), kidney injury molecule 1 (KIM-1), and plasminogen activator inhibitor 1; lipid peroxidation; and renal apoptosis. Treatment with CT-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 neutrophil gelatinase-associated lipocalin. Oxidative stress, a hallmark of CIN, 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, was normal in rats cotreated with CT-1. CT-1 administration significantly prevents the alterations in renal function and structure observed in a rat model of CIN.
authors: Bio-inRen S.L., Salamanca, Spain.
authors: Yaremi
authors: Y
authors: Quiros
authors: Penelope D
authors: PD
authors: Sánchez-González
authors: Francisco J
authors: FJ
authors: López-Hernández
authors: Ana I
authors: AI
authors: Morales
authors: José M
authors: JM
authors: López-Novoa
mesh_terms: D000818:Animals; D003287:Contrast Media / Q000633:toxicity*; D016207:Cytokines / Q000008:administration & dosage*; D007668:Kidney / Q000187:drug effects*; D008297:Male; D051381:Rats; D017208:Rats, Wistar
chemical_list: D003287:Contrast Media; D016207:Cytokines; C092073:cardiotrophin 1