# Mn(III) Porphyrin MnTE-2-PyP5+ Associated with Ascorbate: A Redox-Active Therapeutic Strategy against Leishmaniasis

## TL;DR

This study explores a new treatment for leishmaniasis using a combination of a manganese porphyrin and vitamin C, which reduces parasite growth through oxidative stress.

## Contribution

The study introduces a redox-active therapeutic strategy using MnTE-2-PyP5+ and ascorbate as a potential alternative for leishmaniasis treatment.

## Key findings

- MnP ethyl/Asc reduced promastigote growth by up to 88% in L. amazonensis.
- The treatment increased ROS by 300% and caused mitochondrial depolarization.
- Catalase reversed the effect, confirming H2O2 as the key mediator.

## Abstract

Toxicity and rising
resistance to current leishmaniasis
drugs highlight
the need for alternative therapies. Manganese porphyrins (MnPs) have
demonstrated therapeutic potential in various oxidative stress-based
diseases/ailments due to their redox-modulating properties. Thus,
this study aimed to evaluate the redox-active effects of MnTE-2-PyP5+ (BMX-010, AEOL10113, MnP ethyl) combined with ascorbate
(Asc, vitamin C) on Leishmania amazonensis, Leishmania braziliensis, and Leishmania chagasi
in vitro. The
effects on promastigote growth were assessed, and the mechanism of
action was studied by quantifying reactive oxygen species (ROS) and
using catalase to evaluate H2O2 involvement.
The effects on intracellular amastigotes and the mitochondrial membrane
potential (ΔΨm) of promastigotes from the most susceptible
species were evaluated. Cytotoxicity assays were carried out on mammalian
cells. MnP ethyl alone had no impact on parasite growth; however,
MnP ethyl/Asc treatment led to a significant reduction in the promastigote
growth: 88% for L. amazonensis, 43%
for L. chagasi, and 37% for L. braziliensis after 48 h. MnP ethyl/Asc generated
about 300% more ROS than the untreated control and induced ΔΨm
depolarization. Catalase addition restored parasite survival, confirming
H2O2 as the primary mediator of the MnP ethyl/Asc
effect. Moreover, MnP ethyl/Asc exhibited minimal cytotoxicity on
mammalian cells. The MnP ethyl/Asc treatment reduced the infection
index by about 58% and the number of amastigotes per macrophage by
42% in L. amazonensis after 24 h. These
findings demonstrated that MnP ethyl/Asc exerted an antileishmanial
effect through oxidative stress, providing a promising alternative
for preclinical evaluation.