Repeated Daily Normobaric Hyperoxia: A Non-Pharmacological Strategy Against Gentamicin-Induced Nephrotoxicity

Abstract

Background: Gentamicin (GM) induced nephrotoxicity is one of the most common causes of acute kidney injury and limits its administration. Evidence suggests that pre-treatment with oxygen increases the activity of antioxidant enzymes and protects tissues against different kinds of damage. In this study, the effect of daily normobaric heperoxia pre-treatment on alleviating gentamicin induced nephrotoxicity was investigated. Materials and Methods: Twenty-eight male Wistar rats were randomly divided into four groups (n=7): Control (room air); Gentamicin (100 mg/kg, IP, for 9 days); Hyperoxia60 (60 min daily pretreatment with 95% oxygen and then 100 mg/kg gentamicin, IP, for 9 days) and Hyperoxia180 (180 min daily pretreatment with 95% oxygen and then 100 mg/kg gentamicin, IP, for 9 days). Then 24 h urine was collected and on day 10, the rats were sacrificed for serum, urine and renal tissue sampling. Results: Results showed that hyperoxia significantly enhanced renal antioxidative capacity and decreased serum creatinine and renal failure index. Histological examination and SPECT scan also showed that tissue damage in the hyperoxia groups was lower compared to the gentamicin group. However, hyperoxia effect on body weight, kidney-to-body weight ratio, urine volume, blood urea nitrogen and glomerular filtration was not significant. Conclusion: Although pre-treatment with hyperoxia enhances the antioxidant capacity of renal tissue and improves some of the functional and histopathological parameters of the kidney, it failed to completely restore the adverse effects of gentamicin-induced nephrotoxicity. Thus, more studies are needed to determine the clinical effect of hyperoxia on gentamicin-induced nephrotoxicity.

Keywords

• gentamicin
• nephrotoxicity
• normobaric hyperoxia
• antioxidant