Cardiotrophin-1 therapy prevents gentamicin-induced nephrotoxicity in rats

• Published in: Pharmacological research 2016-05, Vol.107, p.137-146
• Main Authors: Quirós, Yaremi, Blanco-Gozalo, Victor, Sanchez-Gallego, Jose I., López-Hernandez, Francisco J., Ruiz, Juan, Perez de Obanos, María P., López-Novoa, José M.
• Format: Article
• Language: English
• Subjects: Acetylglucosaminidase - urine; Acute kidney injury; Acute Kidney Injury - chemically induced; Acute Kidney Injury - metabolism; Acute Kidney Injury - pathology; Acute Kidney Injury - prevention & control; Acute-Phase Proteins - urine; Aminoglycoside; Animals; Anti-Bacterial Agents; Antigens, CD - metabolism; Antigens, Differentiation, Myelomonocytic - metabolism; Biomarkers - blood; Cardiotrophin-1; Cell Adhesion Molecules - urine; Creatinine - blood; Cytokines - genetics; Cytokines - metabolism; Cytokines - pharmacology; Cytokines - therapeutic use; Gelsolin - urine; Gentamicin; Gentamicins; Kidney - drug effects; Kidney - metabolism; Kidney - pathology; Lipocalins - urine; Male; Nephroprotection; Nitric Oxide Synthase Type II - metabolism; Proto-Oncogene Proteins - urine; Rats; Rats, Wistar; Urea - blood
• ISSN: 1043-6618; 1096-1186
• DOI: 10.1016/j.phrs.2016.02.025

[Display omitted] Aminoglycosides are very effective antibiotics for the treatment of severe infections, but they rank among the most frequent causes of drug-induced nephrotoxicity. Thus, prevention of aminoglycoside nephrotoxicity is an unmet therapeutic objective. Cardiotrophin-1 (CT-1), a member of the IL-6 family of cytokines, has been reported to protect the kidney against toxic and ischemic acute kidney injury (AKI). We have assessed the effect of rat CT-1 in the severity of gentamicin (G)-induced AKI. Groups of male Wistar rats received the following for 6 consecutive days: i) isotonic saline solution (group CONT), ii) G, 150mg/kg/day, i.p. (group G), iii) CT-1, 100μg/kg/day i.v. (group CT-1), or iv) G and CT-1 at the doses described above. The G group showed a manifest AKI characterized by low creatinine clearance, high plasma creatinine and urea levels, increased urinary excretion of proteins, glucose and AKI markers such as N-acetyl-glucosaminidase, neutrophil gelatinase-associated lipocalin, kidney-injury molecule-1 and T-gelsolin, increased kidney levels of CD-68, iNOS, IL-1β and TNF-α, and markedly higher histological renal damage and leukocyte infiltration than the CONT and CT-1 groups. Administration of CT-1 together with G reduced almost all of the above-described manifestations of G-induced AKI. The results of this study have potential clinical application, as CT-1 is near to being used as a drug for organ protection.