 Valeria Cernaro valecern82@virgilio.it 1 Chair of Nephrology, Department of Clinical and Experimental Medicine, University of Messina, Via Consolare Valeria n. 1, 98124 Messina, Italy 2 Department of Veterinary Science, University of Messina, 98100 Messina, Italy 3 IAMC (Institute for Coastal Marine Environment), CNR, U.O.S. Messina, Spianata S. Raineri, 86, 98122 Messina, Italy Received: 11 June 2016 / Accepted: 11 September 2016 © Italian Society of Nephrology 2016 Renoprotective effect of erythropoietin in zebrafsh after administration of gentamicin: an immunohistochemical study for β-catenin and c-kit expression Valeria Cernaro · Alessandra Sfacteria · Claudia Rifci · Francesco Macrì Giulia Maricchiolo · Antonio Lacquaniti · Carlo Alberto Ricciardi Antoine Buemi · Giuseppe Costantino · Domenico Santoro · Michele Buemi J Nephrol DOI 10.1007/s40620-016-0353-y The expression of c-kit and β-catenin sug- gests that erythropoietin may exert a role in regener reducing the extent of tubular damage from the outset a gentamicin administration. Keywords β-Catenin · c-Kit · Erythropoietin · Gentamicin · Tubule regeneration · Zebrafsh Introduction Gentamicin is an aminoglycoside antibiotic widely used against infections caused by Gram-positive and Gram-nega - tive aerobic bacteria. The major factor leading to clinician caution about the use of this drug is its potential neph - toxicity. This occurs in up to 30 % of treated patients can induce a variety of histopathological lesions and clinica pictures [ 1]. The main mechanism responsible for amino - glycoside nephrotoxicity is proximal tubule damage [ 2] that may range from the loss of the epithelial cell brush border t overt tubular necrosis. Tubular obstruction and dysfunc result in their turn in tubuloglomerular feedback activat but this is not suffcient to completely explain the reduced glomerular fltration rate observed in these patients [3]. Indeed, gentamicin also induces renal vasoconstriction and has glomerular effects including mesangial contraction [ 4] and loss of glomerular fltration barrier selectivity, caused by the neutralization of its negative charges [ 5]. Plenty of substances have been examined in a variety of experimental models in order to identify those able t improve the nephrotoxic effects induced by aminoglyco - sides. The purpose of the present study was to evaluat the potential ability of erythropoietin to protect the ki against the damage produced by gentamicin administra - tion in an experimental model of zebrafsh (Danio rerio), Abstract Gentamicin is an aminoglycoside antibiotic widely used in the treatment of infections caused by Gram- negative bacteria. The main limitation to its therapeutic effectiveness is the potential nephrotoxicity. Erythropoi - etin has a tissue protective effect widely demonstrated in the kidney. The aim of the present study was to evaluate the renoprotective effects of erythropoietin in a model of zebrafsh ( ) after administration of gentamicin. Sixty adult zebrafsh were subdivided into three groups: group A was treated with gentamicin; group B received gentamicin and, 24 h later, epoetin alpha; group C received drug diluent only. In order to analyze the renopro - tective activity of erythropoietin, the expression of c-kit and β-catenin was evaluated by immunohistochemistry. Generally, the zebrafsh renal tubule regenerates 15 days after an injury. Conversely, 7 days after gentamicin administration, animals treated with erythropoietin (group B) showed a better renal injury repair as documented by: increased expression of β-catenin, less degenerated tubules, greater number of centers of regeneration, positivity for c-kit only in immature-looking tubules and lymphohema - topoietic cells. 1 3