Leishmania strains causing self-healing cutaneous leishmaniasis have greater susceptibility towards oxidative stress

Area of Science:

• Parasitology
• Immunology
• Medicinal Chemistry

Background:

• Leishmania parasite survival within macrophages is modulated by free radical generation.
• Understanding factors influencing chemotherapeutic response is crucial for treating leishmaniasis.

Purpose of the Study:

• To investigate the influence of free radical generation on the chemotherapeutic response of Leishmania parasites.
• To evaluate the susceptibility of Leishmania isolates from different clinical forms of leishmaniasis to nitric oxide, antimony, and miltefosine.

Main Methods:

• Promastigotes from isolates causing self-healing or delayed/non-self-healing cutaneous leishmaniasis (CL) and visceral leishmaniasis (VL) were tested.
• Susceptibility assays were performed using nitric oxide (NO), antimony, and miltefosine.
• Free radical scavenging capacity and thiol levels were assessed.

Main Results:

• A Leishmania major strain (5ASKH) from self-healing CL showed higher susceptibility to NO and antimony compared to other species.
• A Leishmania amazonensis strain (M2269) also demonstrated greater susceptibility to NO and antimony, but not miltefosine.
• Both 5ASKH and M2269 exhibited poorer free radical scavenging capacity and lower thiol levels than VL-causing species.

Conclusions:

• Self-healing Leishmania isolates appear more susceptible to oxidative stress.
• Parasite susceptibility to certain chemotherapeutics correlates with their free radical scavenging ability and clinical presentation.