Buthionine sulfoximine increases the efficacy of arteether antimalarial activity in arteether-resistant

Background: L-buthionine (S,R)-sulfoximine (BSO) regulates the glutathione (GSH) level, which in turn exhibits remarkable regulation of several important aspects of cellular metabolism. We hypothesised that increasing the cellular levels of glutathione leads to an increased resistance to arteether, whereas decreasing these by using a GSH inhibitor increases the parasite sensitivity to arteether in the rodent malaria parasite Materials and Methods: We tested Results: A relatively stronger inhibition of GSH level was observed in the blood of mice infected with resistant parasites (62.64%; p<0.0001), whereas inhibition in sensitive strain-infected mice and uninfected mice was 32% (p=0.034) and 35% (p=0.034), respectively. The results also show an inverse relationship between GSH and hemozoin in the arteether-sensitive and -resistant strains. The hemozoin contents in the resistant strain are 0.27±0.09, 0.69±0.14 and 5.30±0.79 μmol/10 Conclusions: Treatment with BSO significantly reduces the level of GSH, which leads to insufficient growth of resistant parasites. These results suggest that BSO might be helpful in prolonging the persistence of the drug, and pose a promising lead to help reducing the chance of resistance development against artemisinin and its derivatives.