The Nephroprotective Effect of N-Acetyl-L-Cysteine and Atorvastatin against Imipenem induced Nephrotoxicity.

Abstract

Imipenem has played an important role in the treatment of broad-spectrum bacterial infection. However, nephrotoxicity due to imipenem remains an important clinical challenge. The aim of this study is to test the hypothesis stating that N-acetyl-L-cysteine (NAC) and atorvastatin possess a nephroprotective effect against imipenem-induced nephrotoxicity. Adult Sprague Dawley rats were randomly assigned into six groups (n=8-10 rats/group; total n=55). The groups were (control, imipenem only, NAC only, atorvastatin only, NAC with imipenem, and atorvastatin with imipenem). Rats were treated with NAC or atorvastatin for six weeks. Serum and urinary creatinine and blood urea nitrogen (BUN) levels were measured. Additionally, urinary protein, urinary glucose and kidney levels of oxidants/antioxidants biomarkers were measured. The administration of 300mg/kg/d imipenem induced nephrotoxicity as indicated by the significant reduction of serum creatinine, serum BUN and calculated GFR in the imipenem only-treated group compared to the control. These effects of imipenem were normalized by either NAC or atorvastatin. Moreover, the levels of catalase, superoxide dismutase and glutathione peroxidase were significantly reduced in the imipenem group. However, pre-administration of NAC and atorvastatin neutralized the levels of these enzymes and protected against imipenem-induced nephrotoxicity. We concluded that the pre-administration of either NAC or atorvastatin protects the kidneys from imipenem-induced nephrotoxicity, through their antioxidant effects.