Objective:Mandate from WHO has boosted up anti-filarial drug research.Diethylcarbamazine citrate(DEC) was not known for any direct effect on filarial parasites.However,recent report proposed its direct apoptotic effec...Objective:Mandate from WHO has boosted up anti-filarial drug research.Diethylcarbamazine citrate(DEC) was not known for any direct effect on filarial parasites.However,recent report proposed its direct apoptotic effect.Oxidative stress has been implicated in apoptotic impact.A study was designed to explore the possibility of oxidative rationale to be operative in the direct anti-filarial effect of DEC.Methods:Various doses of DEC and potent oxidant H_2O_2 alone were used in vitro to check for the effects on B.malayi microfilariae,followed by the use of DEC in combination with H_2O_2.Reversal of the oxidative impact of the drug was tested using the antioxidant,vitamin C and also lipid peroxidation levels in the post incubation culture supematants were assayed.Result:As expected,DEC alone failed to record any anti-filarial effect.H_2O_2 alone also failed to show any significant effect until a very high dose was used.However,in combination significant anti-filarial effect was noticed,which allowed even 44%reduction in the dose of H_2O_2.Any significant lipid peroxidation was not found.Vitamin C demonstrated 30%inhibitory effect.Conclusion:DEC and H_2O_2 combination being able to educe synergistic anti-filarial effect and inhibition of the same by vitamin C hinted towards covert oxidative component in the mechanism of DEC.Further implication of non-significant lipid peroxidation was addressed in the perspective of subtle oxidative nexus that seems to be operative in observed anti-filarial effect. Exploration of such rationale might lead to novel drug development.展开更多
基金support from the project "Repository for filarial parasites and reagents", carried out by the project research grants from the Department of Biotechnology(DBT),Govt.of India
文摘Objective:Mandate from WHO has boosted up anti-filarial drug research.Diethylcarbamazine citrate(DEC) was not known for any direct effect on filarial parasites.However,recent report proposed its direct apoptotic effect.Oxidative stress has been implicated in apoptotic impact.A study was designed to explore the possibility of oxidative rationale to be operative in the direct anti-filarial effect of DEC.Methods:Various doses of DEC and potent oxidant H_2O_2 alone were used in vitro to check for the effects on B.malayi microfilariae,followed by the use of DEC in combination with H_2O_2.Reversal of the oxidative impact of the drug was tested using the antioxidant,vitamin C and also lipid peroxidation levels in the post incubation culture supematants were assayed.Result:As expected,DEC alone failed to record any anti-filarial effect.H_2O_2 alone also failed to show any significant effect until a very high dose was used.However,in combination significant anti-filarial effect was noticed,which allowed even 44%reduction in the dose of H_2O_2.Any significant lipid peroxidation was not found.Vitamin C demonstrated 30%inhibitory effect.Conclusion:DEC and H_2O_2 combination being able to educe synergistic anti-filarial effect and inhibition of the same by vitamin C hinted towards covert oxidative component in the mechanism of DEC.Further implication of non-significant lipid peroxidation was addressed in the perspective of subtle oxidative nexus that seems to be operative in observed anti-filarial effect. Exploration of such rationale might lead to novel drug development.
