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. CONCLUSION: 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.
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 ureanitrogen measurements. RESULTS: An approximately twofold elevation in blood ureanitrogen 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. CONCLUSION: 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.
Authors: Mark de Caestecker; Ben D Humphreys; Kathleen D Liu; William H Fissell; Jorge Cerda; Thomas D Nolin; David Askenazi; Girish Mour; Frank E Harrell; Nick Pullen; Mark D Okusa; Sarah Faubel Journal: J Am Soc Nephrol Date: 2015-11-04 Impact factor: 10.121