Role of erythropoietin in prevention of amikacin-induced nephropathy.
BACKGROUND
Aminoglycoside antibiotics are widely used potent bactericidal drugs. However, nephrotoxicity side effects via oxidant injury limit their effectiveness. Erythropoietin (Epo) has been shown to exert pleiotropic effects besides promoting erythrocyte differentiation such as antiapoptotic, antioxidant functions in ischemic and toxic acute renal injury. Therefore we aimed to explore whether Epo is renoprotective in an amikacin-induced nephropathy model in rats.


METHODS
Twenty-eight rats were distributed equally into 4 groups: (i) injected with saline, (ii) injected with amikacin (1.2 g/kg intraperitoneally [i.p.]), (iii) pretreated with Epo (2,000 IU/kg, i.p.) and amikacin (1.2 g/kg i.p.) and (iv) injected only with Epo (2,000 IU/kg, i.p.). Twenty-four hours after last injection, renal tissues were excised for histopathological examinations, and blood samples were collected for serum creatinine and blood urea nitrogen measurements.


RESULTS
An approximately twofold elevation in blood urea nitrogen concentration in the amikacin group (26.6 ± 3.9 mg/dL) compared with saline group (13.1 ± 0.4 mg/dL) was found, reflecting a significant degree of renal dysfunction (p<0.01). Serum urea levels were significantly improved in rats pretreated with Epo (15.9 ± 0.9 mg/dL). The most severe and pronounced injuries based on tubular necrosis were observed in the amikacin group, while rats pretreated with Epo demonstrated marked reduction of the histological features of renal injury.


CONCLUSIONS
As far as we know, the present results are the first to demonstrate a protective effect of exogenous Epo against experimental amikacin-induced renal injury. According to these results, Epo may improve the therapeutic potential of amikacin. More studies are needed for a final conclusion.
Department of Nephrology, School of Medicine, Karadeniz Technical University, Trabzon, Turkey. kkaynar@yahoo.com
Kubra
K
Kaynar
Rezzan
R
Aliyazioglu
Safak
S
Ersoz
Sukru
S
Ulusoy
Sait
S
Al
Gulsum
G
Ozkan
Muammer
M
Cansiz
D000583:Amikacin; D000818:Animals; D015415:Biomarkers / Q000097:blood; D001806:Blood Urea Nitrogen; D003404:Creatinine / Q000097:blood; D019610:Cytoprotection; D004195:Disease Models, Animal; D004921:Erythropoietin / Q000008:administration & dosage / Q000494:pharmacology*; D005260:Female; D007274:Injections, Intraperitoneal; D007275:Injections, Intravenous; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D007674:Kidney Diseases / Q000097:blood / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control*; D009336:Necrosis; D020011:Protective Agents / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000494:pharmacology; D013997:Time Factors
D015415:Biomarkers; D020011:Protective Agents; D011994:Recombinant Proteins; C103998:epoetin beta; D004921:Erythropoietin; D000583:Amikacin; D003404:Creatinine