Renoprotective effect of erythropoietin in zebrafish after administration of gentamicin: an immunohistochemical study for β-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 β-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 β-catenin, less degenerated tubules, greater number of centers of regeneration, positivity for c-kit only in immature-looking tubules and lymphohematopoietic cells.


CONCLUSIONS
The expression of c-kit and β-catenin suggests that erythropoietin may exert a role in regeneration reducing the extent of tubular damage from the outset after gentamicin administration.
Chair of Nephrology, Department of Clinical and Experimental Medicine, University of Messina, Via Consolare Valeria n. 1, 98124, Messina, Italy. valecern82@virgilio.it.
Valeria
V
Cernaro
Department of Veterinary Science, University of Messina, 98100, Messina, Italy.
Alessandra
A
Sfacteria
Department of Veterinary Science, University of Messina, 98100, Messina, Italy.
Claudia
C
Rifici
Department of Veterinary Science, University of Messina, 98100, Messina, Italy.
Francesco
F
Macrì
IAMC (Institute for Coastal Marine Environment), CNR, U.O.S. Messina, Spianata S. Raineri, 86, 98122, Messina, Italy.
Giulia
G
Maricchiolo
Chair of Nephrology, Department of Clinical and Experimental Medicine, University of Messina, Via Consolare Valeria n. 1, 98124, Messina, Italy.
Antonio
A
Lacquaniti
Chair of Nephrology, Department of Clinical and Experimental Medicine, University of Messina, Via Consolare Valeria n. 1, 98124, Messina, Italy.
Carlo Alberto
CA
Ricciardi
Chair of Nephrology, Department of Clinical and Experimental Medicine, University of Messina, Via Consolare Valeria n. 1, 98124, Messina, Italy.
Antoine
A
Buemi
Chair of Nephrology, Department of Clinical and Experimental Medicine, University of Messina, Via Consolare Valeria n. 1, 98124, Messina, Italy.
Giuseppe
G
Costantino
Chair of Nephrology, Department of Clinical and Experimental Medicine, University of Messina, Via Consolare Valeria n. 1, 98124, Messina, Italy.
Domenico
D
Santoro
Chair of Nephrology, Department of Clinical and Experimental Medicine, University of Messina, Via Consolare Valeria n. 1, 98124, Messina, Italy.
Michele
M
Buemi
D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects; D019610:Cytoprotection; D004195:Disease Models, Animal; D000068817:Epoetin Alfa / Q000494:pharmacology*; D005839:Gentamicins; D007150:Immunohistochemistry; D007674:Kidney Diseases / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D007684:Kidney Tubules / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D020011:Protective Agents / Q000494:pharmacology*; D012038:Regeneration / Q000187:drug effects*; D019089:Stem Cell Factor / Q000378:metabolism*; D013997:Time Factors; D015027:Zebrafish; D029961:Zebrafish Proteins / Q000378:metabolism*; D051176:beta Catenin / Q000378:metabolism*
D005839:Gentamicins; D020011:Protective Agents; D019089:Stem Cell Factor; D029961:Zebrafish Proteins; D051176:beta Catenin; C495269:ctnnb1 protein, zebrafish; D000068817:Epoetin Alfa
Erythropoietin; Gentamicin; Tubule regeneration; Zebrafish; c-Kit; β-Catenin
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