Protective Effects of Aminophylline on Vancomycin-Induced Acute Kidney Injury in Rats: Anti-Oxidant and Anti-Inflammatory Roles

Abstract

Background: Vancomycin is currently the antibiotic of choice for serious infections such as methicillin-resistant Staphylococcus aureus (MRSA) and Enterococcus faecium but its usefulness is limited by the development of nephrotoxicity. Aim: The present study was designed to determine the protective roles of aminophylline in vancomycin-induced acute kidney injury (AKI) in rats. Materials and Methods:Male Wister rats (n=40) were used.Vancomycin nephrotoxicity was induced through intraperitoneal injection of vancomycin (200 mg/kg twice daily) for 7 days. Aminophylline was administered once daily in a dose of 24mg/kg alone or combined with vancomycin for 7 days. Results: Vancomycin was observed to cause a severe nephrotoxicity, which was evidenced through increased kidney index, elevated blood urea nitrogen (BUN) and reduced creatinine clearance. Renal malondialdehyde (MDA) levels were significantly increased with marked decrease in renal reduced glutathione (GSH) levels as well as renal superoxide dismutase (SOD) and catalase activities. Moreover, elevated renal tumor necrosis factor-alpha (TNF-α) and low renal interleukin-10 (IL-10) levels were observed. Prior aminophylline administration to rats treated with vancomycin showed significant reduction in kidney index and BUN with elevation in creatinine clearance. In addition, aminophylline reduced elevated renal MDA and TNF-α levels and promoted renal GSH levels in addition to renal SOD and catalase activities with upregulation of renal IL-10. Conclusions: Oxidative stress and inflammation are remarkable pathways in the pathogenesis of vancomycin induced AKI. Aminophylline could be used in a prophylactic manner in vancomycin associated acute renal injury.