Time dependent reduction in gentamicin nephrotoxicity may be unaffected by concurrent artesunate administration

Temidayo Olurishe, Hassan Kunama, Adam Musa. Ahmadu Bello University, Zaria, Kaduna, Nigeria

The oxidative stress related nephrotoxic effects of gentamicin (GM) are reduced with day time administration (Rouguier et al., 2003). GM is an aminoglycoside antibiotic with effective concentration dependent bactericidal effect. Microbiological investigation establishing the presence of GM sensitive bacteria, with malaria co morbidity will necessitate concomitant administration of GM and artesunate (ART) a major antimalaria drug. ART partly owes its antimalaria effects to free radical production from endoperoxide bridge cleavage (Mishra et al., 2007). We hypothesize that ART may negate the beneficial effect of daytime GM administration on renal function and biomarkers.

Non pregnant adult female Wistar rats (n=6) were treated with single daily doses of normal saline (1 ml/kg orally), GM 100 mg/kg (intraperitoneally) and ART 10 mg/kg (orally) alongside GM 100 mg/kg (intraperitoneally) respectively for seven consecutive days. Drug treatment was done during activity period between 1000hrs and 1200hrs daily. Body weight, relative kidney weight and renal biomarkers were determined at the end of treatment period. Animals were euthanized with light chloroform after which kidneys were removed and serum obtained was used for determination of biomarkers using an automated Bayer Analyzer in our Chemical Pathology Laboratory. Data from the study was analysed using ANOVA with Dunnett’s poshoc test.

Data from the study showed that there were no statistically significant differences in serum electrolytes, (namely sodium, chloride, potassium and bicarbonate) and urea. There was also no significant difference in serum albumin (38-40 mmol/l) and total protein (66-70 mmol/l) when treated groups were compared with the saline group. Body weight at start and end of the study also did not differ between groups. However, the relative kidney weights of the GM and GM-ART groups were significantly elevated (p < 0.05) when compared with the saline group at 0.35 and 0.40 percentage of body weight, showing that some nephrotoxic effects were still mediated despite the time of administration.

The ameliorative effect of daytime administration of gentamicin on nephrotoxicity does not appear to be significantly altered by concurrent administration of artesunate at the dose used in the current study.

References

Rougier F, Claude D, Maurin M, Sedoglavic A, Ducher M, Corvaisier S, Jelliffe R and Maire P. (2003). Antimicrob. Agents Chemother., 47(3):1010-1016.

Mishra LC, Bhattacharya A, and virendra K. Bhasin VK (2007). Am. J. Trop. Med. Hyg., 76(3):497–501