Natural sesquiterpene lactones induce oxidative stress on Leishmania mexicana

BARRERA P; SULSEN, VALERIA; LOZANO E; RIVERA M; BEER MF; TONN C; MARTINO V; SOSA MA

EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE

OXFORD UNIV PRESS

Lugar: Oxford; Año: 2013 p. 1 - 6

1741-427X

eishmaniasis is a parasitic disease, worldwide distributed and is caused by monoflagellate parasites of the genus Leishmania. In the search for effective agents against parasites, it has been attempted to identify molecular targets, to ensure the efficiency of the drugs and to avoid collateral damages on the host cells. In this work, we have tried to explain some of the mechanisms of action of sesquiterpene lactones that are effective against promastigotes of Leishmania mexicana mexicana, through one of the most vulnerable points on the trypanosomatids; their particular defense system against oxidative stress. We first observed that the antiproliferative effect of mexicanin (Mxc), dehydroleucodine (DhL), and psilostachyin (Psi), but at lesser extent psilostachyin C (Psi C), is blocked by 1.5 mM reduced glutathione. The reducing agent was also able to reverse the early effect of compounds, suggesting that lactones may interfere with sulfhydryl groups inside the cells. Moreover, we have shown that all sesquiterpene lactones, except Psi C, decreased significantly concentrations of endogenous molecules carrying reduced thiol groups in parasites. Consistent with these findings, the active lactones increased between 2.7 and 5.4 times the generation of ROS by parasites. These results indicate that the induction of oxidative stress is at least one of the mechanisms of action of DhL, Mxc and Psi on parasites and that Psi C could act by other mechanisms.