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| Author(s): |
Sarah Santos de Lima Melchert
Total Authors: 1
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| Document type: | Master's Dissertation |
| Press: | São Paulo. |
| Institution: | Universidade de São Paulo (USP). Faculdade de Medicina (FM/SBD) |
| Defense date: | 2024-03-12 |
| Examining board members: |
Luiz Felipe Domingues Passero;
André Gustavo Tempone Cardoso;
João Henrique Ghilardi Lago;
Marcia Dalastra Laurenti
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| Advisor: | Luiz Felipe Domingues Passero |
| Abstract | |
This work aims to evaluate the sensitivity of different species to 8-hydroxyquinoline (8-HQ), formulate a cream containing 8-HQ for topical use, and evaluate its effectiveness in experimentally detected leishmaniasis. Studies with L. (L.) amazonensis, L. (L.) infantum, L. (V.) guyanensis, L. (V.) lainsoni, L. (V.) naiffi and L. (V.) shawi discoveries that 8-HQ was selected in promastigotes and amastigotes after 24 and 72 h of incubation, with species of the subgenus Viannia were more susceptible to the compound; Furthermore, 8-HQ was more selective than miltefosine in all species evaluated. Infected macrophages treated with 8-HQ produced NO mainly within 72 h, indicating that the molecule has an immunomodulatory action. 8-HQ was formulated based on Beeler at 1 and 2% and from a physical point of view, it was observed that the 2% cream contained larger particles than the 1% cream and only the cream without the addition of 8-HQ. Permeation experiments on porcine skin revealed a higher steady-state flux (g/cm²/h), permeability coefficient (cm²/h) and diffusion coefficient (cm/h) of the 1% cream compared to 2%. The diffusion coefficient of 1 and 2% creams in artificial membrane and porcine skin was higher than the 8-HQ EC50 for L. (L.) amazonensis, indicating that both have permeation capacity at EC50 to exert a leishmanicidal action in vivo. There were no histological changes in porcine skin exposed to the cream during the demonstrative permeation test, and when tested in BALB/c mice, the creams did not induce macroscopic or histological changes in the skin. To evaluate the effectiveness of the creams, BALB/c mice were infected at the base of the tail with L. (L.) amazonensis and after 4 weeks they were subjected to topical treatment with creams containing 1 or 2% 8-HQ for 14 days. Compared to infected control animals; it was observed that treatment with 1 or 2% creams reduced the size of the lesion in the animals and the parasite load in the skin and inguinal lymph nodes. It is noteworthy that in the last week of treatment, the 1% cream showed more significant reductions in the size of the lesion compared to the other groups, reducing the size of the lesions by 56.4% in relation to the infected group. Intralesional treatment with Glucantime® (50 mg/kg) was used as a control and demonstrated a reduction in the diameter of the lesions and the parasitic load of the animals. In immunological evaluation, control groups produced high levels of IL-4 and low levels of IFN-, correlated with a diffuse inflammatory infiltrate in the skin, with a high density of amastigotes and areas of tissue necrosis. On the other hand, treatment with 1 and 2% creams caused a reduction in tissue amastigotes, associated with moderate inflammatory infiltrate and low density of infected macrophages; in addition to a decrease in IL-4 levels and an increase in IFN-. Treatment with Glucantime® also reduced the parasite load, IL-4 levels and an increase in IFN-. However, an intense inflammatory infiltrate and tissue necrosis areas were observed in intralesional treatment. Therefore, topical treatment with 1 and 2% was effective in the treatment of experimental cutaneous leishmaniasis and can be considered an alternative treatment for this neglected disease (AU) | |
| FAPESP's process: | 21/02392-0 - Topical treatment of experimental cutaneous leishmaniasis with the 8-hydroxyquinoline |
| Grantee: | Sarah Santos de Lima Melchert |
| Support Opportunities: | Scholarships in Brazil - Master |