Sinefungin as Treatment for American Leishmania in Sensitive BALB/c and Resistant C57BL/6 Mice

José Luis AvilaInstituto de Biomedicina, Caracas, Venezuela

Search for other papers by José Luis Avila in
Current site
Google Scholar
PubMed
Close
,
Tamara RojasInstituto de Biomedicina, Caracas, Venezuela

Search for other papers by Tamara Rojas in
Current site
Google Scholar
PubMed
Close
,
Héctor MonzónInstituto de Biomedicina, Caracas, Venezuela

Search for other papers by Héctor Monzón in
Current site
Google Scholar
PubMed
Close
, and
Jacinto ConvitInstituto de Biomedicina, Caracas, Venezuela

Search for other papers by Jacinto Convit in
Current site
Google Scholar
PubMed
Close
Restricted access

Using inbred BALB/c and C57BL/6 mice as animal models for American cutaneous leishmaniasis, we evaluated the inhibitory effect of sinefungin on foot-pad infection produced by 5 different Leishmania isolates. When treatment was initiated a few days, or even 2 weeks, after infection, an obvious leishmanicidal effect was detected on mice infected with Leishmania mexicana or L. braziliensis isolates, which lasted at least 50 weeks for all isolates studied. The optimal dose schedule was 4 mg/kg body weight/day, injected ip for 10 consecutive days; lower doses produced only a short leishmanistatic effect. The optimal dose found was 50-fold lower than the LD50. In vitro studies using Leishmania-infected murine peritoneal macrophages showed sinefungin as a powerful inhibitory drug, mean ED50 for the several Leishmania isolates studied being 50 ng/ml. No correlation was found between in vitro sensitivity of culture promastigotes and in vivo sensitivity to sinefungin of an American Leishmania isolate.

Save