Angiotensin II Receptor Blocker, Losartan, Ameliorates Gentamicin-Induced Oxidative Stress and Nephrotoxicity in Rats

BACKGROUND/AIMS: This study investigates the ameliorative effect of concurrent and pretreatment with angiotensin II receptor blocker, losartan (LOS), against gentamicin (GEN)-induced renal damage. METHODS: Rats were divided into five groups: control, LOS group (10 mg/kg/day for 7 days), GEN group (100 mg/kg/day for 7 days), GEN + LOS pretreated group (treated with LOS for 7 days followed by 7 days of GEN), and GEN + LOS concurrently treated group (simultaneously treated with GEN and LOS for 7 days). RESULTS: Concurrent treatment with LOS significantly reduced urine volume, microalbuminuria, blood urea nitrogen (BUN) and serum creatinine levels elevated by GEN administration. Also, LOS significantly attenuated GEN-induced increase in malondialdehyde and decrease in reduced glutathione, and catalase and superoxide dismutase activities in renal cortical homogenates. Additionally, histopathological examination and scoring showed that LOS markedly ameliorated GEN-induced renal tubular damage. Conversely, pretreatment with LOS produced no significant changes in urine volume, microalbuminuria, BUN and serum creatinine with little changes in the oxidative stress parameters when compared with the GEN-treated group. CONCLUSION: Concurrent treatment with LOS has produced marked amelioration in biochemical indices and oxidative stress parameters against GEN-induced nephrotoxicity. Accordingly, LOS can be considered a feasible antihypertensive drug for hypertensive patients simultaneously treated with GEN.