title: Cardiotrophin-1 therapy prevents gentamicin-induced nephrotoxicity in rats.
abstract: 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.
authors.affiliation: Bio-inRen S.L., Salamanca, Spain.
authors.forename: Yaremi
authors.initials: Y
authors.lastname: Quirós
authors.affiliation: Bio-inRen S.L., Salamanca, Spain.
authors.forename: Victor
authors.initials: V
authors.lastname: Blanco-Gozalo
authors.affiliation: Bio-inRen S.L., Salamanca, Spain.
authors.forename: Jose I
authors.initials: JI
authors.lastname: Sanchez-Gallego
authors.affiliation: Unidad de Fisiopatología Renal y Cardiovascular, Departamento de Fisiología y Farmacología, Universidad de Salamanca, Salamanca, Spain; Instituto de Investigación Biomédica de Salamanca (IBSAL), Salamanca, Spain; Instituto de Estudios de Ciencias de la Salud de Castilla y León (IESCYL), Salamanca, Spain.
authors.forename: Francisco J
authors.initials: FJ
authors.lastname: López-Hernandez
authors.affiliation: Digna Biotech S.L., Madrid, Spain.
authors.forename: Juan
authors.initials: J
authors.lastname: Ruiz
authors.affiliation: Digna Biotech S.L., Madrid, Spain.
authors.forename: María P
authors.initials: MP
authors.lastname: Perez de Obanos
authors.affiliation: Unidad de Fisiopatología Renal y Cardiovascular, Departamento de Fisiología y Farmacología, Universidad de Salamanca, Salamanca, Spain; Instituto de Investigación Biomédica de Salamanca (IBSAL), Salamanca, Spain. Electronic address: jmlnovoa@usal.es.
authors.forename: José M
authors.initials: JM
authors.lastname: López-Novoa
mesh_terms: D000118:Acetylglucosaminidase / Q000652:urine; D058186:Acute Kidney Injury / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D000209:Acute-Phase Proteins / Q000652:urine; D000818:Animals; D000900:Anti-Bacterial Agents; D015703:Antigens, CD / Q000378:metabolism; D015214:Antigens, Differentiation, Myelomonocytic / Q000378:metabolism; D015415:Biomarkers / Q000097:blood; D015815:Cell Adhesion Molecules / Q000652:urine; D003404:Creatinine / Q000097:blood; D016207:Cytokines / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology / Q000627:therapeutic use*; D018260:Gelsolin / Q000652:urine; D005839:Gentamicins; D007668:Kidney / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D000071068:Lipocalin-2; D054834:Lipocalins / Q000652:urine; D008297:Male; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000652:urine; D051381:Rats; D017208:Rats, Wistar; D014508:Urea / Q000097:blood; D000097382:CD68 Molecule
chemical_list: D000118:Acetylglucosaminidase; D000209:Acute-Phase Proteins; D000900:Anti-Bacterial Agents; D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D015415:Biomarkers; D015815:Cell Adhesion Molecules; D003404:Creatinine; D016207:Cytokines; D018260:Gelsolin; D005839:Gentamicins; D000071068:Lipocalin-2; D054834:Lipocalins; D052247:Nitric Oxide Synthase Type II; D011518:Proto-Oncogene Proteins; D014508:Urea; C539355:CD68 protein, rat; D000097382:CD68 Molecule; C110936:Havcr1 protein, rat; C097278:Lcn2 protein, rat; C092073:cardiotrophin 1; C496318:Nos2 protein, rat
keywords: Acute kidney injury; Aminoglycoside; Cardiotrophin-1; Gentamicin; Nephroprotection