Effect of Certain Antibiotics Against Filarial Parasite Brugia malayi In Vitro: Possible Role of Oxidative Stress

Abstract

WHO-Tropical Disease Research scheme highlighted the need for development of new anti-filarial drugs. Certain antibiotics have recently been found effective against Wolbachia, co-existing symbiotically with filarial parasites. Inflammatory response entails oxidative mechanism to educe direct anti-microbial effect. In the present study microfilariae were maintained in vitro in medium supplemented with varying concentrations of tetracycline, doxycycline (20-100 μg/ml) or ciprofloxacin (50-250 μg/ml) separately to find out any involvement of oxidative mechanism in the anti-filarial effect of these antibiotics. Loss of motility of the microfilariae was measured after 48 h and correlated with the levels of MDA, nitric oxide and protein-carbonylation. Significant loss of microfilarial motility was recorded with increasing concentration of tetracycline and doxycycline but with ciprofloxacin the effect was not marked. Agents with high antifilarial activity revealed significant association with oxidative parameters in a dose dependent manner. The result suggests that oxidative effect might be exploited to design novel antifilarial drug candidate.

Keywords: Antibiotics; B. malayi; Drug design; Oxidative stress.

Fig. 1

a MDA levels of antibiotics (nM/ml) in culture supernatants obtained after 48 h incubation with each of the antibiotics. MDA levels in control (RPMI medium): 2.5 nM/ml (tetracycline: y = 0.0426x, R² = 8153; doxycycline: y = 0.0333x, R² = 0.9464). b Carbonyl content of antibiotics (nmol/mg of protein) in culture supernatants obtained after 48 h incubation with each of the antibiotics. Carbonyl content in control (RPMI medium): 0.0244 nM/mg of protein (tetracycline: y = 0.0077x, R² = 0.8465; doxycycline: y = 0.0025x, R² = 0.2349). c Nitric oxide levels of antibiotics (in mM/ml) in culture supernatants obtained after 48 h incubation with each of the antibiotics. Control value (RPMI): 0.0004 mM/ml (tetracycline: y = 0.0008x, R² = 0.847; doxycycline: y = 0.0009x, R² = 0.9477)