Therapeutic trial in experimental tegumentary leishmaniasis caused by Leishmania (Leishmania) amazonensis. A comparative study between mefloquine and aminosidine

Abstract

One hundred and eighty-two male inbred C57/BL/6 mice were infected with 3 x 106 Leishmania (Leishmania) amazonensis promastigotes of the MHOM/BR/PH8 strain by means of a subcutaneous injection in the right ear. The animals were separated in three groups: 1) oral mefloquine hydrochloride treatment (16mg/kg/day/10 days), 2) intramuscular aminosidine (Paromomycin®) treatment (20mg/kg/20 days) and 3) control. Twenty six mice of each treated group were sacrificed, one at the end of treatment (nine weeks after inoculation), and one six weeks later (fifteen weeks after inoculation). Control Group animals were sacrificed at weeks six, nine and fifteen after inoculation. There was no significant difference between Group 1 (mefloquine) and Group 3 (control) subjects. Group 2 animals (aminosidine) presented the smallest differences of all, both at the end of the treatment and six weeks later. The histopato-logical parameters have shown the following findings: a) there was no significant difference between the mefloquine treated group and the control group; the group treated with aminosidine showed fewer of vacuolated macrophages than the control group, at week 9 (end of treatment). b) both at the end of treatment and six weeks later, evaluation of tissue necrosis and tissue fibrosis revealed no differences between the treated groups. It was found that six weeks after the end of treatment, mice in the control group presented significantly more severe degrees of fibrosis than mice in the other groups. It can be concluded that mefloquine showed limited therapeutic effect in this experimental model, whereas aminosidine had a significant effect. Nevertheless, neither of them resulted in cure of the lesions.

Development of a semi-automated image-based high-throughput drug screening system

“…Mefloquine hydrochloride is a medication used to prevent malaria. However, mefloquine hydrochloride was inactive against Leishmania amazonensis in vivo (32). One of the hits is pentamidine isethionate, which is a well-known anti-leishmanial drug (33).…”

Activity of antimalarial drugs in vitro and in a murine model of cutaneous leishmaniasis

“…However, the pharmacological effect of mefloquine in Leishmania infection remains controversial. According to Galvão et al (2000) and Laguna-Torres et al (1999), oral treatment with mefloquine had a limited therapeutic effect in C57BL/6 mice infected with L. amazonensis , as well as in the treatment of human cutaneous leishmaniasis caused by Leishmania braziliensis . However, Landires et al (1995) reported a promising therapeutic effect of mefloquine in human cutaneous leishmaniasis caused by Leishmania panamensis .…”

Programmed Cell Death Ligand (PD-L)-1 Contributes to the Regulation of CD4+ T Effector and Regulatory T Cells in Cutaneous Leishmaniasis

“…Infectivity of parasites was maintained through animal passage and parasites were used for infection after maximum five passages in culture. Viable parasites were counted, washed with PBS (pH 7.0), and the concentration was adjusted to 3 × 10 6 parasites in 10 µL volume, as described previously in other publications (37)(38)(39). Mice were kept under isoflurane/oxygen, the left ear was exposed, and 10 µL parasitedose were injected.…”