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

Abstract

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.

Keywords

gentamicin / nephrotoxicity / antioxidants / experimental peritonitis

References

[1] Камышников B.C. Клинико-биохимическая лабораторная диагностика. Справочник. В 2 т. 2-е изд. Мн.: Интерпрессервис. 2003; 2: 463 с.

[2] Лакин Г.Ф. Биометрия. Учебное пособие для биологических специальных вузов. 4-е изд., перераб. и доп. М.: Высшая школа. 1990; 352 с.

[3] Руководство по экспериментальному (доклиническому) изучению новых фармакологических веществ. Под ред. Р.У. Хабриева. 2-изд., перераб. и доп. М.: Медицина. 2005; 832 с.

[4] Ali B.H. Agents ameliorating or augmenting experimental gentamicin nephrotoxicity: some recent research. Food Chem. Toxicol. 2003; 41: 1447-1452. http://dx.doi.org/10.1016/S0278-6915(03)00186-8

[5] Banday A.A., Farooq N., Priyamvada S. et al. Time dependent effects of gentamicin on the enzymes of carbohydrate metabolism, brush border membrane and oxidative stress in rat kidney tissues. Life Sci. 2008; 82: 450-459. http://dx.doi.org/10.1016/j.lfs.2007.11.014

[6] Ben Ismail T.H., Ali B.H., Bashir A.A. Influence of iron, deferoxamine and ascorbic acid on gentamicin-induced nephrotoxicity in rats. Gen. Pharmacol. 1994; 25 (6): 1249-1252. http://dx.doi.org/10.1016/0306-3623(94)90145-7

[7] Cachofeiro V., Goicochea M., de Vinuesa S.G. et al. Oxidative stress and inflammation, a link between chronic kidney disease and cardiovascular disease. Kidney Int. 2008; suppl.: S4-S9. http://dx.doi.org/10.1038/ki.2008.516

[8] De la Cruz Rodríguez L.C., Araujo C.R., Posleman S.E. et al. Attenuation of gentamicin-induced nephrotoxicity: trimetazidine versus N-acetyl cysteine. J. Appl. Toxicol. 2010; 30 (4): 343-353. http://dx.doi.org/10.1002/jat.1502

[9] Hanaa M., El-Fattah A., El-Sheikh N.M. Evaluation of chemoprotective role of N-acetylcysteine and vitamin E on gentamicin-induced nephrotoxicity. Australian J. Basic Applied Sci. 2012; 6 (3): 263-270.

[10] Kohanski M.A., Dwyer D.J., Hayete B. et al. A common mechanism of cellular death induced by bactericidal antibiotics. Cell. 2007; 130: 797-810. http://dx.doi.org/10.1016/j.cell.2007.06.049

[11] Koyner J.L., Sher Ali R., Murray P.T. Antioxidants. Do they have a place in the prevention or therapy of acute kidney injury? Nephron Exp. Nephrol. 2008; 109: e109-e117. http://dx.doi.org/10.1159/000142935

[12] Morales A.I., Detaille D., Prieto M. et al. Metformin prevents experimental gentamicin-induced nephropathy by a mitochondria-dependent pathway. Kidney Int. 2010; 77: 861-869. http://dx.doi.org/10.1038/ki.2010.11

[13] Selby N.M., Shaw S., Woodier N. et al. Gentamicin-associated acute kidney injury. QJ. Med. 2009; 102: 873-880. http://dx.doi.org/10.1093/qjmed/hcp143

[14] Stojiljkovic N., Stoiljkovic M., Randjelovic P. et al. Cytoprotective effect of vitamin C against gentamicin-induced acute kidney injury in rats. Exp. Toxicol. Pathol. 2012; 64 (1-2): 69-74. http://dx.doi.org/10.1016/j.etp.2010.06.008

RIGHTS & PERMISSIONS

Miroshnichenko A.G., Brukhanov V.M., Gossen I.Y., Perfilyev V.Y.