Oxymatrine Reverses Gentamicin-Induced Nephrotoxicity via Ameliorating the Immune Response for Gentamicin Therapy

Abstract Background: The aminoglycoside antibiotic gentamicin (GM) is widely used to fight infections caused by Gram-positive and Gram-negative aerobic bacteria. However, its clinical application is limited by serious side effects. Based on this, this study aims to screen drugs that have protective effects on gentamicin-induced kidney injury. Methods : After screening a series of candidate compounds, we found that a natural quinoline alkaloid-oxymatrine showed well protective effects on GM-induced kidney injury. We used gentamicin (100 mg/ kg/d, 7 days) treatment to establish a rat model of kidney injury, and set up control groups and oxymatrine-pretreatment groups to study the protective effect of oxymatrine on kidney injury.Methods: After screening a series of candidate compounds, we found that a natural quinoline alkaloid-oxymatrine showed well protective effects on GM-induced kidney injury. We used gentamicin (100 mg/ kg/d, 7 days) treatment to establish a rat model of kidney injury, and set up control groups and oxymatrine-pretreatment groups to study the protective effect of oxymatrine on kidney injury.Results: The results indicated that Gentamicin treatment of normal rats produced marked renal damage and resulted in significant elevation of blood urea nitrogen and creatinine, as well as N-acetyl-β-D-glucosaminidase. Oxymatrine co-administration could decrease levels of IL-1β, IL-6, and TNF-α (All P <0.01 or P <0.001), as well as N-acetyl-β-D-glucosaminidase. In addition, oxymatrine treatment significantly reduced the expression of Bax and NF-κB mRNA in the kidney (both P <0.01), and increased the expression of Bcl-2, Nrf2 and HO-1 mRNA.Conclusions: The results demonstrate that oxymatrine down-regulates the inflammatory response and reduces the apoptosis by activating antioxidant defense, thereby reducing gentamicin-induced nephrotoxicity.