Ultrastructural alterations induced by the neolignan dihydrobenzofuranic eupomatenoid-5 on epimastigote and amastigote forms of Trypanosoma cruzi

Luize, Patrícia Shima; Ueda-Nakamura, Tânia; Filho, Benedito Prado Dias; Cortez, Diógenes Aparı́cio Garcia; Morgado‐Díaz, José Andrés; Souza, Wanderley de

doi:10.1007/s00436-006-0241-9

Cited by 27 publications

(17 citation statements)

References 18 publications

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“…with different inhibitors of sterol synthesis led to alterations in the organization of chromatin and to the presence of myelinlike figures and autophagosome-like structures suggesting the involvement of an autophagic cell death process (Lazardi et al, 1990;Vannier-Santos et al, 1995;Braga et al, 2004;Granthon et al, 2007;Rodrigues et al, 2007). In epimastigotes, the natural neolignan dihydrobenzofuranic eupomatenoid-5 induced characteristic features of an autophagic process (Luize et al, 2006). Our images obtained from the treatment of T. cruzi with different drugs showed alterations indicative of different cell death pathways.…”

Section: Discussionmentioning

confidence: 86%

Different cell death pathways induced by drugs in Trypanosoma cruzi: An ultrastructural study

Menna-Barreto

Salomão

Dantas

et al. 2009

Micron

139

109

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Section: Discussionmentioning

confidence: 86%

Different cell death pathways induced by drugs in Trypanosoma cruzi: An ultrastructural study

Menna-Barreto

Salomão

Dantas

et al. 2009

Micron

139

109

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“…1), a neolignan isolated from leaves of Piper regnellii var. pallescens [13,14]. As a consequence of these alterations, eupomatenoid-5 inhibited the growth of epimastigotes and intracellular amastigotes.…”

Section: Introductionmentioning

confidence: 99%

Trypanocidal action of eupomatenoid-5 is related to mitochondrion dysfunction and oxidative damage in Trypanosoma cruzi

Pelizzaro-Rocha¹,

Veiga-Santos²,

Lazarin-Bidóia³

et al. 2011

Microbes and Infection

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Because of its severe side effects and variable efficacy, the current treatment for Chagas disease is unsatisfactory. Natural compounds are good alternative chemotherapeutic agents for the treatment of this infection. Recently, our group reported the antiproliferative activity and morphological alterations in epimastigotes and intracellular amastigotes of Trypanosoma cruzi treated with eupomatenoid-5, a neolignan isolated from leaves of Piper regnellii var. pallescens. Here, we demonstrate that eupomatenoid-5 exhibited activity against trypomastigotes, the infective form of T. cruzi (EC₅₀ 40.5 μM), leading to ultrastructural alteration and lipoperoxidation in the cell membrane. Additionally, eupomatenoid-5 induced depolarization of the mitochondrial membrane, lipoperoxidation and increased G6PD activity in epimastigotes of T. cruzi. These findings support the possibility that different mechanisms may be targeted, according to the form of the parasite, and that the plasma membrane and mitochondria are the structures that are most affected in trypomastigotes and epimastigotes, respectively. Thus, the trypanocidal action of eupomatenoid-5 may be associated with mitochondrial dysfunction and oxidative damage, which can trigger destructive effects on biological molecules of T. cruzi, leading to parasite death.

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“…Ultrathin sections of intracellular tachyzoites of Toxoplasma gondii treated with quinuclidine derivatives showing a complete destruction of the mitochondrion. interferes with epimastigotes and amastigotes of T. cruzi [81]. In Fig.…”

Section: Mitochondrionmentioning

confidence: 91%

Ultrastructural Alterations in Organelles of Parasitic Protozoa Induced by Different Classes of Metabolic Inhibitors

Rodrigues

Souza²

2008

CPD

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Parasitic protozoa such as Leishmania, Trypanosoma, Plasmodium, Toxoplasma gondii, Giardia and Trichomonas are able to cause several diseases affecting millions of people around the world with dramatic consequences to the socio-economic life of the affected countries. Diseases like malaria, leishmaniasis and trypanosomiasis have been classified by the World Health Organization as neglected diseases, because they have been almost completely forgotten by the governments as well as the pharmaceutical companies. The specific chemotherapy currently employed for the treatment of these diseases has serious limitations due to lack of efficacy, toxic side effects, growth of drug-resistance and high costs. Thus, it is urgent to develop new chemotherapeutic agents that are more effective, safe and accessible. In this context, several works have been focused on understanding the effect of different drug-treatments on these parasitic protozoa. Organelles and structures such as mitochondrion, kinetoplast, apicoplast, glycosome, acidocalcisome, hydrogenosome, plasma membrane and the cytoskeleton have been studied using different approaches to identify new targets for the development of new chemotherapeutic agents that are required. Some studies on alterations in the fine structure, as assayed using electron microscopy, have indicated the nature of lesions induced by several drugs, allowing deductions on possible modes of action. Here, we briefly review the available data of the effects of several drugs on the ultrastructure of parasitic protozoa and show how electron microscopy can contribute to elucidate the different mechanisms of these anti-parasitic drugs.

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Ultrastructural alterations induced by the neolignan dihydrobenzofuranic eupomatenoid-5 on epimastigote and amastigote forms of Trypanosoma cruzi

Cited by 27 publications

References 18 publications

Different cell death pathways induced by drugs in Trypanosoma cruzi: An ultrastructural study

Different cell death pathways induced by drugs in Trypanosoma cruzi: An ultrastructural study

Trypanocidal action of eupomatenoid-5 is related to mitochondrion dysfunction and oxidative damage in Trypanosoma cruzi

Ultrastructural Alterations in Organelles of Parasitic Protozoa Induced by Different Classes of Metabolic Inhibitors

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