Renoprotective effect of erythropoietin in zebrafish after administration of gentamicin: an immunohistochemical study for ?-catenin and c-kit expression

Background: 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. Erythropoietin 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 zebrafish (Danio rerio) after administration of gentamicin. Methods: Sixty adult zebrafish 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 renoprotective activity of erythropoietin, the expression of c-kit and ?-catenin was evaluated by immunohistochemistry. Results: Generally, the zebrafish 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 ?-catenin, less degenerated tubules, greater number of centers of regeneration, positivity for c-kit only in immature-looking tubules and lymphohematopoietic cells. Conclusion: The expression of c-kit and ?-catenin suggests that erythropoietin may exert a role in regeneration reducing the extent of tubular damage from the outset after gentamicin administration.