Intermediate reactive oxygen and nitrogen from macrophages induced by Brazilian lichens

Santos, Lourdes Campaner dos; Honda, Nobuaki; Carlos, Iracilda Zeppone; Vilegas, Wagner

doi:10.1016/j.fitote.2004.04.002

Cited by 30 publications

(47 citation statements)

References 14 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Possibly the effects of epoxy-␣-lapachone in the control of lesions in mice are due to multifactorial actions on parasite physiology. The chemical structures of naphthoquinone derivatives, such as the compound in this study, contribute to the formation of reactive oxygen and accelerate intracellular hypoxic conditions, causing severe damage to the parasite cells (34,35).…”

Section: Discussionmentioning

confidence: 98%

Epoxy-α-Lapachone Has In Vitro and In Vivo Anti-Leishmania (Leishmania) amazonensis Effects and Inhibits Serine Proteinase Activity in This Parasite

Souza-Silva

Bourguignon

Pereira

et al. 2015

Antimicrob Agents Chemother

View full text Add to dashboard Cite

Leishmania (Leishmania) amazonensis is a protozoan that causes infections with a broad spectrum of clinical manifestations. The currently available chemotherapeutic treatments present many problems, such as several adverse side effects and the development of resistant strains. Natural compounds have been investigated as potential antileishmanial agents, and the effects of epoxy-␣-lapachone on L. (L.) amazonensis were analyzed in the present study. This compound was able to cause measurable effects on promastigote and amastigote forms of the parasite, affecting plasma membrane organization and leading to death after 3 h of exposure. This compound also had an effect in experimentally infected BALB/c mice, causing reductions in paw lesions 6 weeks after treatment with 0.44 mM epoxy-␣-lapachone (mean lesion area, 24.9 ؎ 2.0 mm 2 ), compared to untreated animals (mean lesion area, 30.8 ؎ 2.6 mm 2 ) or animals treated with Glucantime (mean lesion area, 28.3 ؎ 1.5 mm 2 ). In addition, the effects of this compound on the serine proteinase activities of the parasite were evaluated. Serine proteinase-enriched fractions were extracted from both promastigotes and amastigotes and were shown to act on specific serine proteinase substrates and to be sensitive to classic serine proteinase inhibitors (phenylmethylsulfonyl fluoride, aprotinin, and antipain). These fractions were also affected by epoxy-␣-lapachone. Furthermore, in silico simulations indicated that epoxy-␣-lapachone can bind to oligopeptidase B (OPB) of L. (L.) amazonensis, a serine proteinase, in a manner similar to that of antipain, interacting with an S1 binding site. This evidence suggests that OPB may be a potential target for epoxy-␣-lapachone and, as such, may be related to the compound's effects on the parasite.

show abstract

Section: Discussionmentioning

confidence: 98%

Epoxy-α-Lapachone Has In Vitro and In Vivo Anti-Leishmania (Leishmania) amazonensis Effects and Inhibits Serine Proteinase Activity in This Parasite

Souza-Silva

Bourguignon

Pereira

et al. 2015

Antimicrob Agents Chemother

View full text Add to dashboard Cite

show abstract

“…The compounds I, II and V were more representative in the production of this mediator; all of them showed a significative liberation of NO, approximately 23, 90 and 13 µmols/5 x 10 5 cells, respectively (p < 0.001). It is important to notice that compound V was also derivatived from compound II (Santos et al, 2004). The compound [2] (protocetraric acid) presents three functions: alcohol, acid and aldehyde that were modified in this study and showed high production of NO.…”

Section: Resultsmentioning

confidence: 82%

“…Compounds isolated from fungi had been shown to enhance immune response through the up-regulation of nitric oxide from peritoneal macrophages acting as an effective immunomodulator and an anti-tumoral agent. (Suzuki et al, 1985;Kim et al, 2004;Santos et al, 2004;Gao et al, 2005;Zheng et al, 2005). Since the symbiotic association of algae with fungus forms lichens and there are just few works about the pharmacological properties of lichens, in this research we decided to study pure compounds isolated from Brazilian lichens and their derivatives.…”

Section: Introductionmentioning

confidence: 99%

Immunostimulatory effects of the phenolic compounds from lichens on nitric oxide and hydrogen peroxide production

Carlos¹,

Carli²,

Maia³

et al. 2009

Rev. bras. farmacogn.

View full text Add to dashboard Cite

de peróxido de hidrogênio e óxido nítrico". Os efeitos dos compostos isolados de líquens brasileiros e seus derivados na produção de NO e H 2 O 2 foram estudados utilizando macrófagos murinos na tentativa de desvendar suas possíveis propriedades imunomodulatórias. A citotoxicidade dos compostos foi estudada utilizando o ensaio de MTT. A estimulação dos macrófagos foi avaliada através da determinação de NO (metodologia de Griess) e H 2 O 2 (peroxidase de raíz forte/vermelho de fenol) no sobrenadante de culturas de macrófagos peritoneais de camundongos Swiss. Este estudo demonstrou atividade estimulante de alguns compostos fenólicos e seus derivados na produção de NO e H 2 O 2 . A relação estrutura atividade sugere inúmeras direções sintéticas para futuros melhoramentos da atividade imunológica.Unitermos: líquens, peróxido de hidrogênio, óxido nítrico, macrófagos, compostos fenólicos. ABSTRACT:The effects of isolated compounds from Brazilian lichens and their derivatives on H 2 O 2 and NO production were studied using murine macrophages as a part of an attempt to understand their possible immunomodulatory properties. The compound cytotoxicity was studied using MTT assay. Macrophage stimulation was evaluated by the determination of NO (Griess assay) and H 2 O 2 (horseradish peroxidase/phenol red) in supernatants of peritoneal macrophage cultures of Swiss mice. This research demonstrated stimulatory activities of some phenolic compounds isolated from lichens and their derivatives on H 2 O 2 and NO production. Structure-activity relationships suggest several synthetic directions for further improvement of immunological activity.

show abstract

“…Usnic acid was initially used in the treatment of pulmonary tuberculosis (Plichet, 1955), and there are data regarding its biological activities as an antibiotic (Cocchietto et al, 2002), antiproliferative (Carderelli et al, 1997), analgesic and antipyretic (Okuyama et al, 1995), antiinflammatory (Vijayakumar et al, 2000), antiviral (Campanella et al, 2002;Scirpa et al, 1999), antifungal (Halama and Haluwin, 2004), against the parasite Trypanosoma cruzi (Carvalho et al, 2005) and as an immunologic modulator (Santos et al, 2004). Antitumor activity of usnic acid was shown for the first time by Kupchan and Kopperman (1975) against Lewis lung carcinoma in mice.…”

Section: Introductionmentioning

confidence: 99%

Does usnic acid affect microtubules in human cancer cells?

et al. 2010

View full text Add to dashboard Cite

Usnic acid, a lichen metabolite, is known to exert antimitotic and antiproliferative activities against normal and malignant human cells. Many chemotherapy agents exert their activities by blocking cell cycle progression, inducing cell death through apoptosis. Microtubules, protein structure involved in the segregation of chromosomes during mitosis, serve as chemotherapeutical targets due to their key role in cellular division as well as apoptosis. The aim of this work was to investigate whether usnic acid affects the formation and/or stabilisation of microtubules by visualising microtubules and determining mitotic indices after treatment. The breast cancer cell line MCF7 and the lung cancer cell line H1299 were treated with usnic acid 29 µM for 24 hours and two positive controls: vincristine (which prevents the formation of microtubules) or taxol (which stabilizes microtubules). Treatment of MCF7 and H1299 cells with usnic acid did not result in any morphological changes in microtubules or increase in the mitotic index. These results suggest that the antineoplastic activity of usnic acid is not related to alterations in the formation and/or stabilisation of microtubules.Keywords: usnic acid, microtubules, breast cancer, lung cancer. O ácido úsnico pode afetar microtúbulos em células cancerosas humanas?Resumo O ácido úsnico, um metabólito de liquens, é conhecido por sua atividade antimitótica e antiproliferativa em células humanas normais e malignas. Muitos quimioterápicos exercem suas atividades bloqueando a progressão do ciclo celular e induzindo morte celular por apoptose. Os microtúbulos, estruturas protéicas envolvidas na segregação dos cromossomos durante a mitose, servem como alvo quimioterapêutico devido ao seu importante papel tanto na divisão celular quanto nos mecanismos de morte celular por apoptose. O objetivo deste trabalho foi investigar se o ácido úsnico afeta a formação e/ou estabilização dos microtúbulos, a partir da visualização de microtúbulos e determinação de índices mitóticos após o tratamento. Células de câncer de mama MCF7 e de câncer de pulmão H1299 foram tratadas por 24 horas com 29 µM de ácido úsnico e dois controles positivos: vincristina (que impede a formação de microtúbulos) e taxol (que estabiliza microtúbulos). O tratamento das células MCF7 e H1299 com o ácido úsnico não resultou em aumento do índice mitótico. Os resultados sugerem que a atividade antineoplásica do ácido úsnico não está relacionada a alterações na formação e/ou estabilização de microtúbulos.Palavras-chave: ácido úsnico, microtúbulos, câncer de mama, câncer de pulmão.

show abstract

Intermediate reactive oxygen and nitrogen from macrophages induced by Brazilian lichens

Cited by 30 publications

References 14 publications

Epoxy-α-Lapachone Has In Vitro and In Vivo Anti-Leishmania (Leishmania) amazonensis Effects and Inhibits Serine Proteinase Activity in This Parasite

Epoxy-α-Lapachone Has In Vitro and In Vivo Anti-Leishmania (Leishmania) amazonensis Effects and Inhibits Serine Proteinase Activity in This Parasite

Immunostimulatory effects of the phenolic compounds from lichens on nitric oxide and hydrogen peroxide production

Does usnic acid affect microtubules in human cancer cells?

Contact Info

Product

Resources

About