Antioxidants capabilities in correction of gentamicin-induced nephrotoxicity in experimental infection

Aim. To assess the antioxidants effectiveness (ascorbic acid, methylethylpiridinol, N-acetylcysteine) in reducing the gentamicin-induced nephrotoxicity in experimental infection caused by Escherichia coli or Klebsiella pneumoniae.

Methods. The experiment was divided into two parts. In the first part, the effect of antioxidants on the sensitivity of bacteria to gentamicin in vitro according to changing the optical density of the bacterial suspension, in the second part - nephroprotective activity of antioxidants and their effects on antibiotic activity in experimental bacterial peritonitis were evaluated.

Results. All antioxidants significantly reduce the sensitivity of E. coli to gentamicin in vitro, and the level of effect is directly proportional to the antioxidant concentration. Methylethylpiridinol has the most pronounced antagonistic action against gentamicin. It is found that methylethylpiridinol at a concentration of 4 mmol/l enhances development of Escherichia coli strain by 7 times by the 6th hour of incubation. Ascorbic acid and N-acetylcysteine have a similar probacterial activity profile. In the incubation mixtures containing a strain of Klebsiella pneumoniae, a similar pattern of increase in bacterial biomass optical density was observed with maximum values in the presence of the highest concentrations of antioxidants. In experimental infection, antioxidants reduce the activity of gentamicin against Escherichia coli and Klebsiella pneumoniae, without reducing the antibiotic nephrotoxicity.

Conclusion. Ascorbic acid, methylethylpiridinol and N-acetylcysteine reduce the antibacterial activity of gentamicin against Escherichia coli and Klebsiella pneumoniae in vitro and in vivo, in a dose of 80 mg/kg they do not reduce gentamicin nephrotoxicity in bacterial peritonitis in rats; their use in the course of treatment with gentamicin is not only irrational, but also contraindicated.