The Role of Oxidative Stress in the Pathogenesis and Treatment of Leishmaniasis: Impact on Drug Toxicity and Therapeutic Potential of Natural Products
Abstract
1. Introduction
2. Human Infection by the Leishmania Parasite, Immune Response, and Oxidative Stress
3. Treatment of Leishmaniasis and Possible Involvement of Oxidative Stress
4. New Therapeutic Alternatives for the Treatment of Leishmaniasis and Their Toxic Potential
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
Abbreviations
LC | Cutaneous leishmaniasis |
LV | Visceral leishmaniasis |
GLP | Glycosylphosphatidylinositol |
CRP | C-reactive protein |
CR4 | Complement receptor 4 |
PKC | Protein kinase C |
CL | Langerhans cells |
LTA | American tegumentary leishmaniasis |
NO | Nitric oxide |
NOS2 | Nitric oxide synthase type 2 |
ROS | Reactive oxygen species |
O2− | Superoxide anions |
H2O2 | Hydrogen peroxide |
NADPH oxidase | Nicotinamide Adenine Dinucleotide Phosphate Oxidase |
O2 | Molecular oxygen |
RNS | Reactive nitrogen species |
TXNPx | Thioredoxin peroxidase |
FeSOD | Iron superoxide dismutase |
MA | Meglumine antimoniate |
ZnNPs | Zinc nanoparticles synthesized by green synthesis |
CC50 | 50% cytotoxic concentration |
HEVS | Hexane extract |
SI | Selectivity index |
IC50 | 50% inhibitory concentration |
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Samples | Antileishmania Activity | Toxicity Profile | SI | Mechanism of Action | |
---|---|---|---|---|---|
Promastigote | Amastigote | ||||
Virola surinamensis (hexanic extract) | IC50 = 86.40 µg/mL (L. chagasi), 79.7 ± 1.3 µg/mL (L. amazonensis) | Inactive | (CC50 > 500 µg/mL) Low toxicity | >5.78 >6.27 | Modulation of oxidative stress and apoptosis in the parasite |
(-)-5-Demethoxygrandisin B | IC50 = 7.0 µM | IC50 = 26.04 µM | (CC50 = 26.04 µM) High selectivity, low toxicity | 3.7 | Mitochondrial damage, interaction with TryR |
β-Sitosterol | IC50 = 17.7 ± 0.43 µg/mL | Induction of apoptosis | (>500 µg/mL) Low toxicity | >28.2 | Increased ROS and mitochondrial depolarization |
Sterculia villosa (methanolic extract) | IC50 = 17.5 µg/mL | DNA fragmentation | Low toxicity | ND | ROS overproduction and oxidative stress |
Flavopereirine (Geissospermum vellosii) | IC50 = 0.23 µg/mL (24 h) | IC50 = 0.15 µg/mL (72 h) | (CC50 = 499.3 µg/mL) High selectivity | 3328.7 | Inhibition of oligopeptidase B |
Aspidosperma nitidum (ethanol extract) | IC50 = 23.87 µg/mL | Reduction of parasite load in vivo | (CC50 = 500 µg/mL) in vitro No toxicity in vivo | 21 | Inhibition of trypanothione reductase, apoptosis |
Aspidosperma nitidum (alkaloidal fraction) | IC50 = 18.5 µg/mL | Reduction of parasite load in vivo | (CC50 = 200 µg/mL) in vitro No toxicity in vivo | 11 | Inhibition of trypanothione reductase, apoptosis |
Artemether (ART) | IC50 = 16.43 µg/mL | IC50 = 37.12 µg/mL | Reduced toxicity | ND | Interference in mitochondrial phosphorylation |
Artemether (NLC-ART) | IC50 = 15.42 µg/mL | IC50 = 32.1 µg/mL | Reduced toxicity | ND | Interference in mitochondrial phosphorylation |
Salidroside (Rhodiola spp.) | Reduction of promastigote growth | Reduction of parasite load | Low liver and kidney toxicity | ND | Modulation of the immune response, increased NO and ROS |
Iridoid glycosides (Nyctanthes arbortristis) | Induction of apoptosis via oxidative stress | ROS-induced cell death | Low cytotoxicity in normal cells | ND | Mitochondrial oxidative damage, apoptosis |
HO-3867 (Curcumin analogue) | Cell cycle arrest | Interruption of intracellular charge | Low cytotoxicity to macrophages | ND | Disruption of the STAT3 pathway and activation of apoptotic pathways |
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Brígido, H.P.C.; dos Santos, L.G.A.; de Barros, R.C.; Correa-Barbosa, J.; Santos, P.V.B.d.; Paz, R.F.L.; Pereira, A.R.; Albuquerque, K.C.O.d.; Campos, M.B.; Silveira, F.T.; et al. The Role of Oxidative Stress in the Pathogenesis and Treatment of Leishmaniasis: Impact on Drug Toxicity and Therapeutic Potential of Natural Products. Toxics 2025, 13, 190. https://doi.org/10.3390/toxics13030190
Brígido HPC, dos Santos LGA, de Barros RC, Correa-Barbosa J, Santos PVBd, Paz RFL, Pereira AR, Albuquerque KCOd, Campos MB, Silveira FT, et al. The Role of Oxidative Stress in the Pathogenesis and Treatment of Leishmaniasis: Impact on Drug Toxicity and Therapeutic Potential of Natural Products. Toxics. 2025; 13(3):190. https://doi.org/10.3390/toxics13030190
Chicago/Turabian StyleBrígido, Heliton Patrick Cordovil, Laís Gabrielly Abreu dos Santos, Renilson Castro de Barros, Juliana Correa-Barbosa, Paulo Victor Barbosa dos Santos, Rayana Franciele Lopes Paz, Amanda Ramos Pereira, Kelly Cristina Oliveira de Albuquerque, Marliane Batista Campos, Fernando Tobias Silveira, and et al. 2025. "The Role of Oxidative Stress in the Pathogenesis and Treatment of Leishmaniasis: Impact on Drug Toxicity and Therapeutic Potential of Natural Products" Toxics 13, no. 3: 190. https://doi.org/10.3390/toxics13030190
APA StyleBrígido, H. P. C., dos Santos, L. G. A., de Barros, R. C., Correa-Barbosa, J., Santos, P. V. B. d., Paz, R. F. L., Pereira, A. R., Albuquerque, K. C. O. d., Campos, M. B., Silveira, F. T., Percário, S., & Dolabela, M. F. (2025). The Role of Oxidative Stress in the Pathogenesis and Treatment of Leishmaniasis: Impact on Drug Toxicity and Therapeutic Potential of Natural Products. Toxics, 13(3), 190. https://doi.org/10.3390/toxics13030190