Cardiotrophin-1 therapy prevents gentamicin-induced nephrotoxicity in rats

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• 作者：Yaremi Quiró ; s^a ; Victor Blanco-Gozalo^a ; Jose I. Sanchez-Gallego^a ; Francisco J. Ló ; pez-Hernandez^b ; ^c ; ^d ; Juan Ruiz^e ; Marí ; a P. Perez de Obanos^e ; José ; M. Ló ; pez-Novoa^b ; ^c ; ^{jmlnovoa@usal.es" class="auth_mail" title="E-mail the corresponding author}
• 关键词：Acute kidney injury ; Aminoglycoside ; Cardiotrophin-1 ; Gentamicin ; Nephroprotection
• 刊名：Pharmacological Research
• 出版年：2016
• 出版时间：May 2016
• 年：2016
• 卷：107
• 期：Complete
• 页码：137-146
• 全文大小：3016 K

文摘

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, 150 mg/kg/day, i.p. (group G), iii) CT-1, 100 μg/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.