Background and Objective: 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.
Methods: 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.
Results: 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.
Conclusion: We concluded that the pre-administration of either NAC or atorvastatin protects the kidneys
from imipenem-induced nephrotoxicity, through their antioxidant effects.