Visceral leishmaniasis caused by Leishmania (Leishmania) amazonensis associated with Hodgkin’s lymphoma

Pôrto, Victor Bertollo Gomes; Carvalho, Laína Bubach; Buzo, Bruno Fernando; Litvoc, Marcelo Nóbrega; Santos, Ana Catharina S.; Rocci, Rafael Avila; Soares, Sandra Regina; Zampieri, Ricardo Andrade; Duarte, Maria Irma Seixas; Lindoso, José Ângelo Lauletta

doi:10.1590/s1678-9946202264051

Cited by 4 publications

(5 citation statements)

References 15 publications

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“…The clinical manifestations of this illness depend on the host’s immune background and status [ 5 ]. For instance, Leishmania amazonenis is the etiologic agent of either localized or diffuse CL in Brazil; however, it has also been implicated in the etiology of VL in immunosuppressed patients, including those with hematologic disorders [ 6 ]. Another relevant issue is the phenotypical and genotypical backgrounds of the Leishmania isolates/species, which will drive the ability to express mechanisms of resistance as well as different and multiple virulence factors to cause more or less severe clinical manifestations [ 5 ].…”

Section: Introductionmentioning

confidence: 99%

Silver(I) and Copper(II) 1,10-Phenanthroline-5,6-dione Complexes as Promising Antivirulence Strategy against Leishmania: Focus on Gp63 (Leishmanolysin)

et al. 2023

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Leishmaniasis, caused by protozoa of the genus Leishmania, encompasses a group of neglected diseases with diverse clinical and epidemiological manifestations that can be fatal if not adequately and promptly managed/treated. The current chemotherapy options for this disease are expensive, require invasive administration and often lead to severe side effects. In this regard, our research group has previously reported the potent anti-Leishmania activity of two coordination compounds (complexes) derived from 1,10-phenanthroline-5,6-dione (phendione): [Cu(phendione)3].(ClO4)2.4H2O and [Ag(phendione)2].ClO4. The present study aimed to evaluate the effects of these complexes on leishmanolysin (gp63), a virulence factor produced by all Leishmania species that plays multiple functions and is recognized as a potential target for antiparasitic drugs. The results showed that both Ag-phendione (−74.82 kcal/mol) and Cu-phendione (−68.16 kcal/mol) were capable of interacting with the amino acids comprising the active site of the gp63 protein, exhibiting more favorable interaction energies compared to phendione alone (−39.75 kcal/mol) or 1,10-phenanthroline (−45.83 kcal/mol; a classical gp63 inhibitor) as judged by molecular docking assay. The analysis of kinetic parameters using the fluorogenic substrate Z-Phe-Arg-AMC indicated Vmax and apparent Km values of 0.064 µM/s and 14.18 µM, respectively, for the released gp63. The effects of both complexes on gp63 proteolytic activity were consistent with the in silico assay, where Ag-phendione exhibited the highest gp63 inhibition capacity against gp63, with an IC50 value of 2.16 µM and the lowest inhibitory constant value (Ki = 5.13 µM), followed by Cu-phendione (IC50 = 163 µM and Ki = 27.05 µM). Notably, pretreatment of live L. amazonensis promastigotes with the complexes resulted in a significant reduction in the expression of gp63 protein, including the isoforms located on the parasite cell surface. Both complexes markedly decreased the in vitro association indexes between L. amazonensis promastigotes and THP-1 human macrophages; however, this effect was reversed by the addition of soluble gp63 molecules to the interaction medium. Collectively, our findings highlight the potential use of these potent complexes in antivirulence therapy against Leishmania, offering new insights for the development of effective treatments for leishmaniasis.

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Section: Introductionmentioning

confidence: 99%

Silver(I) and Copper(II) 1,10-Phenanthroline-5,6-dione Complexes as Promising Antivirulence Strategy against Leishmania: Focus on Gp63 (Leishmanolysin)

et al. 2023

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“…A report of visceral leishmaniasis in a human patient with a lung tumor highlights leishmaniasis as a possibility to be considered in the diagnosis of causes of fever in patients undergoing chemotherapy in an endemic area [59]. In humans, visceral leishmaniasis was also reported in association with Hodgkin's lymphoma [60], melanoma…”

Section: Tumor and Leishmania Infection Associationmentioning

confidence: 99%

Current Challenges in the Association between Canine Leishmaniasis and Malignant Disorders

Silva Ribeiro,

de Oliveira Cardoso,

Lucia Abreu-Silva

et al. 2024

Leishmania Parasites - Epidemiology, Immunopathology and Hosts

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Neoplasms in dogs are estimated to account for up to 83% of all canine malignancies, while canine leishmaniasis is endemic and highly incident in areas like Brazil, east Africa, and India. The worldwide incidence of both diseases may indicate the presence of these two pathologies in the same tissue sample as eventual cases. However, a relationship between leishmaniasis and malignant disorders has been postulated in human and veterinary medicine. Depending on several direct or indirect factors, leishmaniasis can affect the clinical manifestation, diagnosis, therapeutic protocols, and the outcome of various malignant disorders. In addition, the similarity of the clinical presentation of cutaneous or visceral leishmaniasis with the clinical signs observed in many tumors may lead to misdiagnosis. Clinical cases of co-localization of Leishmania parasites and tumor cells in dogs were more associated with transmissible venereal tumors than histiocytic tumors, non-histiocytic lymphoma, or squamous cell carcinoma. This chapter reviews the circumstances involving canine leishmaniasis and malignant disorders, and the current challenge that the association between them represents to misdiagnosis or tumor-promoting potential of leishmaniasis, providing an overview of dog cases.

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“…Among them, cutaneous leishmaniasis is the most common, and characterized by a wide range of clinical variations because of the involvement of the skin and mucous membranes of individuals (de Vries et al, 2015;Ornellas-Garcia et al, 2023). In this work, we used the species L. amazonensis, which is related to all types of clinical manifestations of leishmaniasis (Gatti et al, 2017;Gonçalves et al, 2023;Porto et al, 2022;Valdivia et al, 2017).…”

Section: Introductionmentioning

confidence: 99%

“…In this work, we used the species L . amazonensis , which is related to all types of clinical manifestations of leishmaniasis (Gatti et al., 2017; Gonçalves et al., 2023; Porto et al., 2022; Valdivia et al., 2017).…”

Section: Introductionmentioning

confidence: 99%

4‐Quinolinylhydrazone analogues kill Leishmania (Leishmania) amazonensis by inducing apoptosis and mitochondria‐dependent pathway cell death

Granato,

Silva,

Lemos

et al. 2024

Chem Biol Drug Des

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Despite efforts, available alternatives for the treatment of leishmaniasis are still scarce. In this work we tested a class of 15 quinolinylhydrazone analogues and presented data that support the use of the most active compound in cutaneous leishmaniasis caused by Leishmania amazonensis. In general, the compounds showed activity at low concentrations for both parasitic forms (5.33–37.04 μM to promastigotes, and 14.31–61.98 μM to amastigotes). In addition, the best compound (MHZ15) is highly selective for the parasite. Biochemical studies indicate that the treatment of promastigotes with MHZ15 leads the loss of mitochondrial potential and increase in ROS levels as the primary effects, which triggers accumulation of lipid droplets, loss of plasma membrane integrity and apoptosis hallmarks, including DNA fragmentation and phosphatidylserine exposure. These effects were similar in the intracellular form of the parasite. However, in this parasitic form there is no change in plasma membrane integrity in the observed treatment time, which can be attributed to metabolic differences and the resilience of the amastigote. Also, ultrastructural changes such as vacuolization suggesting autophagy were observed. The in vivo effectiveness of MHZ15 in the experimental model of cutaneous leishmaniasis was carried out in mice of the BALB/c strain infected with L. amazonensis. The treatment by intralesional route showed that MHZ15 acted with great efficiency with significantly reduction in the parasite load in the injured paws and draining lymph nodes, without clinical signs of distress or compromise of animal welfare. In vivo toxicity was also evaluated and null alterations in the levels of hepatic enzymes aspartate aminotransferase, and alanine aminotransferase was observed. The data presented herein demonstrates that MHZ15 exhibits a range of favorable characteristics conducive to the development of an antileishmanial agent.

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Visceral leishmaniasis caused by Leishmania (Leishmania) amazonensis associated with Hodgkin’s lymphoma

Cited by 4 publications

References 15 publications

Silver(I) and Copper(II) 1,10-Phenanthroline-5,6-dione Complexes as Promising Antivirulence Strategy against Leishmania: Focus on Gp63 (Leishmanolysin)

Silver(I) and Copper(II) 1,10-Phenanthroline-5,6-dione Complexes as Promising Antivirulence Strategy against Leishmania: Focus on Gp63 (Leishmanolysin)

Current Challenges in the Association between Canine Leishmaniasis and Malignant Disorders

4‐Quinolinylhydrazone analogues kill Leishmania (Leishmania) amazonensis by inducing apoptosis and mitochondria‐dependent pathway cell death

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