An organogold compound impairs Leishmania amazonensis amastigotes survival and delays lesion progression in murine cutaneous leishmaniasis: Mechanistic insights

Autor(es):Mostrar menos -

Minori, Karen ; Gadelha, Fernanda R. ; Bonsignore, Riccardo ; Alcantar, Guillermo Moreno ; Fontes, Josielle, V ; Abbehausen, Camilla ; Brioschi, Mariana B. C. ; de Sousa, Lizandra Maia ; Consonni, Silvio R. ; Casini, Angela ; Miguel, Danilo C.

• Tipo de documento: Artigo Científico
• Fonte: Biochemical Pharmacology; v. 232, p. 9-pg., 2024-12-16.

Resumo

Leishmaniasis is one of the most important neglected diseases, classically characterized by three clinical forms that if left untreated can lead to skin lesions, lifelong scarring, or death depending on the parasite species. Unfortunately, treatment is unsatisfactory and the search for an improved therapy has been a priority. Gold compounds have emerged as promising candidates and among them, Au(I)bis-N-heterocyclic carbene (Au (BzTMX)2) has stood out. We have shown that it alters the plasma membrane permeability of Leishmania amazonensis and L. braziliensis, with superior activity for L. amazonensis. Herein, we moved a step forward towards the elucidation of its mechanism of action in L. amazonensis axenic amastigotes in vitro and in vivo. After 24 h incubation, Au(BzTMX)2 induced changes in safranin O uptake, reflecting the ultrastructural changes observed in mitochondria, especially cristae swelling, and oxygen consumption rates. Besides mitochondrial alterations, plasma membrane blebbing and the formation of multilamellar structures were also observed suggesting an autophagy-like process induction. In vivo, Au(BzTMX)2 was capable of delaying lesion progression, decreasing the total ulcerated area and leading to a marked reduction in the parasite burden of infected BALB/c mice. Taking all into consideration, our results give support to the current knowledge of the importance of gold compounds in therapeutics and open new possibilities for leishmaniasis treatment. (AU)

• Processo FAPESP: 21/01504-9 - Efeitos da paridade e da idade na condrogênese e na osteogênese da sínfise púbica em camundongos: uma abordagem morfológica e molecular de potenciais fatores de risco para o prolapso de órgãos pélvicos
• Beneficiário: Sílvio Roberto Consonni
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 22/06410-5 - Complexos metálicos como inibidores enzimáticos específicos para o tratamento da Leishmaniose: cisteína protease e tripanotiona redutase
• Beneficiário: Josielle Vieira Fontes
• Modalidade de apoio: Bolsas no Brasil - Doutorado
• Processo FAPESP: 22/02618-0 - Desenvolvimento de novos metalofármacos e formas de administração inovadoras para tratamento de Leishmaniose
• Beneficiário: Camilla Abbehausen
• Modalidade de apoio: Auxílio à Pesquisa - Projeto Inicial
• Processo FAPESP: 14/21129-4 - O papel das proteínas ligantes de ácidos graxos na infecção de macrófagos por Leishmania: um alvo potencial para novas drogas contra leishmaniose
• Beneficiário: Danilo Ciccone Miguel
• Modalidade de apoio: Auxílio à Pesquisa - Jovens Pesquisadores