Amentoflavone as an Ally in the Treatment of Cutaneous Leishmaniasis: Analysis of Its Antioxidant/Prooxidant Mechanisms
| Autor: | Flávia de Oliveira Cardoso, Yasmin Silva Rizk, Sandy Santos-Pereira, Carlos Alexandre Carollo, Kátia da Silva Calabrese, Carla Cardozo Pinto de Arruda, Marcelo Pelajo-Machado, Luiza F. O. Gervazoni, Tânia Zaverucha-do-Valle, Elmo E. Almeida-Amaral, Celeste da Silva Freitas de Souza, Daiana de Jesus Hardoim |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
Microbiology (medical) intralesional treatment Immunology lcsh:QR1-502 Leishmaniasis Cutaneous Amentoflavone Pharmacology Microbiology lcsh:Microbiology Antioxidants Nitric oxide 03 medical and health sciences chemistry.chemical_compound cutaneous leishmaniasis Mice 0302 clinical medicine Cellular and Infection Microbiology Cutaneous leishmaniasis In vivo medicine prooxidant amentoflavone Animals Biflavonoids antileishmanial activity Amastigote IC50 Leishmaniasis Original Research chemistry.chemical_classification Leishmania Mice Inbred BALB C Glucantime Biflavonoid medicine.disease biflavonoid 030104 developmental biology Infectious Diseases chemistry 030220 oncology & carcinogenesis Toxicity Reactive Oxygen Species |
| Zdroj: | Frontiers in Cellular and Infection Microbiology Frontiers in Cellular and Infection Microbiology, Vol 11 (2021) |
| ISSN: | 2235-2988 |
| Popis: | Treatment of leishmaniasis is a challenging subject. Although available, chemotherapy is limited, presenting toxicity and adverse effects. New drugs with antileishmanial activity are being investigated, such as antiparasitic compounds derived from plants. In this work, we investigated the antileishmanial activity of the biflavonoid amentoflavone on the protozoan Leishmania amazonensis. Although the antileishmanial activity of amentoflavone has already been reported in vitro, the mechanisms involved in the parasite death, as well as its action in vivo, remain unknown. Amentoflavone demonstrated activity on intracellular amastigotes in macrophages obtained from BALB/c mice (IC50 2.3 ± 0.93 μM). No cytotoxicity was observed and the selectivity index was estimated as greater than 10. Using BALB/c mice infected with L. amazonensis we verified the effect of an intralesional treatment with amentoflavone (0.05 mg/kg/dose, in a total of 5 doses every 4 days). Parasite quantification demonstrated that amentoflavone reduced the parasite load in treated footpads (46.3% reduction by limiting dilution assay and 56.5% reduction by Real Time Polymerase Chain Reaction). Amentoflavone decreased the nitric oxide production in peritoneal macrophages obtained from treated animals. The treatment also increased the expression of ferritin and decreased iNOS expression at the site of infection. Furthemore, it increased the production of ROS in peritoneal macrophages infected in vitro. The increase of ROS in vitro, associated with the reduction of NO and iNOS expression in vivo, points to the antioxidant/prooxidant potential of amentoflavone, which may play an important role in the balance between inflammatory and anti-inflammatory patterns at the infection site. Taken together these results suggest that amentoflavone has the potential to be used in the treatment of cutaneous leishmaniasis, working as an ally in the control and development of the lesion. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|