Ultrastructural alterations and peroxide formation induced by naphthoquinones in different stages ofTrypanosoma cruzi

Abstract

Addition of beta-lapachone, an o-naphthoquinone with bactericidal, cytotoxic, and trypanocidal activities, to Trypanosoma cruzi epimastigote and amastigote stages induced the release of O2- and H2O2 from the whole cells into the suspending medium. In the presence of reduced nicotinamide adenine dinucleotide as reductant beta-lapachone was also able to stimulate O2- and H2O2 production by homogenates of these stages. Electron micrographs showed that in beta-lapachone-treated amastigotes and trypomastigotes, the chromatin is arranged in patches, clearly differing from the normal pattern of chromatin distribution. Alterations of the nuclear, mitochondrial, and cytoplasmic membranes, as well as swelling of the mitochondria were also observed.

Effects of a marine serine protease inhibitor on viability and morphology of Trypanosoma cruzi, the agent of Chagas disease

“…Here, we demonstrated morphological features closely similar to the autophagic phenomena previously studied in T. cruzi after treatment with drugs (Lazardi et al, 1990;Santa-Rita et al, 2005;Menna-Barreto et al, 2009b). These data together with the absence of typical morphological characteristics of apoptosis or necrosis such as chromatin condensation, blebbing of the plasma membrane or membrane rupture are suggestive of autophagy as part of the mechanism of action of ShPI-I in the parasite (Docampo et al, 1978;Menna-Barreto et al, 2009b) (Fig. 4).…”

Effects of a novel β–lapachone derivative on Trypanosoma cruzi : Parasite death involving apoptosis, autophagy and necrosis

“…Nevertheless it may furnish significant insights for the infection chemotherapy, as β-lapachone was reported to produce similar alterations in T. cruzi epimastigotes, amastigotes and trypomastigotes (Docampo et al., 1978), the developmental forms that multiply within mammalian host cells and spread via blood, respectively. In addition, different antiparasitic compounds may display similar effects upon epimastigotes and trypomastigotes and/or amastigotes, the developmental forms (Urbina et al., 1988, Urbina et al., 1993; Moreira et al., 2013a; Costa et al., 2011, Azeredo et al., 2014, Díaz et al., 2014; Jimenez et al., 2014; Veiga-Santos et al., 2014, Britta et al., 2015, Meira et al., 2015, Volpato et al., 2015, Beer et al., 2016) and the epimastigotes may therefore comprise and/or take part in experimental models (Kessler et al., 2013, Benítez et al., 2014, Sangenito et al., 2014, Wong-Baeza et al., 2015, Khare et al., 2015, Pessoa et al., 2016, Valera Vera et al., 2016).…”

“…Natural plant-derived quinones and their derivatives may exert multifactorial effects upon distinct targets on antiparasitic chemotherapy (Pinto and Castro, 2009, Salas et al., 2008, Belorgey et al., 2013). Naphtoquinones such as β–lapachone are natural products isolated from different higher plant families and shown to present antimalarial (Carvalho et al., 1988, De Andrade-Neto et al., 2004, Pérez-Sacau et al., 2005), giardicidal (Corrêa et al., 2009), leishmanicidal (Guimarães et al., 2013) and trypanocidal activity against T. brucei (De Pahn et al., 1988) and Trypanosoma cruzi (Boveris et al., 1978, Docampo et al., 1978, Goijman and Stoppani, 1985, Pinto et al., 1997, Pinto et al., 2000, Menna-Barreto et al., 2005, Menna-Barreto et al., 2007, Menna-Barreto et al., 2009a, 2014). Furthermore, lapachone derivatives/analogues may display enhanced antiparasitic activity upon T. cruzi (Pinto et al., 1997; Ferreira et al., 2011, Diogo et al., 2013).…”

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

“…The trypanocidal activity of b-lapachone is related to free radical generation and inhibition of macromolecule biosynthesis (Boveris et al, 1978;Lopes et al, 1978;Goijman and Stoppani, 1985). The treatment of the three forms of T. cruzi, with this naphthoquinone led to alterations of chromatin distribution, mitochondrion and plasma membrane (Docampo et al, 1977(Docampo et al, , 1978a alterations which are suggestive of an apoptosis-like process.…”