Plasmodium falciparum: Erythrocytic stages die by autophagic-like cell death under drug pressure

Totino, Paulo Renato Rivas; Daniel-Ribeiro, Cláudio Tadeu; Cortê-Real, Suzana; Ferreira-da-Cruz, Maria de Fátima

doi:10.1016/j.exppara.2007.10.017

Cited by 67 publications

(65 citation statements)

References 40 publications

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“…The apoptosis mechanism of P. falciparum in erythrocytic stages is not fully elucidated, although there are some reports of apoptosis using existing drugs, such a chloroquine and staurosporine. [20][21][22][23] Recently, it was reported that macrolide antibiotics, such as azithromycin, caused the 'delayed death' of P. falciparum and their target was the apicoplast. [24][25][26] Although borrelidin is also a macrolide, its mode of action may well be different because borrelidin did not show 'delayed death' in this experiment.…”

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confidence: 99%

Borrelidin, a potent antimalarial: stage-specific inhibition profile of synchronized cultures of Plasmodium falciparum

et al. 2011

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confidence: 99%

Borrelidin, a potent antimalarial: stage-specific inhibition profile of synchronized cultures of Plasmodium falciparum

et al. 2011

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“…However，there is the possibility that L-Arg acts directly on the viability of malaria parasite. It was reported that P. falciparum parasites under the pressure of S-nitroso-N-acetyl-penicillamine (SNAP), the NO donor, died by autophagic-like cell death (Totino et al 2008). Another study showed that NO production increased in P. falciparum parasites incubated with L-Arg in vitro (Rey et al 2014).…”

Section: Discussionmentioning

confidence: 95%

L-Arginine Exacerbates Experimental Cerebral Malaria by Enhancing Pro-Inflammatory Responses

Feng

Chen³

et al. 2015

Tohoku J. Exp. Med.

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L-Arginine (L-Arg), the substrate for nitric oxide (NO) synthase, has been used to treat malaria to reverse endothelial dysfunction in adults. However, the safety and efficacy of L-Arg remains unknown in malaria patients under the age of five, who are at the greatest risk of developing cerebral malaria (CM), a severe malaria complication. Here, we tested effects of L-Arg treatment on the outcomes of CM using a mouse model. Experimental cerebral malaria (ECM) was induced in female C57BL/6 mice infected with Plasmodium berghei ANKA, and L-Arg was administrated either prophylactically or after parasite infection. ) in the spleen. The levels of pro-inflammatory cytokines, IFN-γ and TNF-α, in splenocyte cultures were also increased by L-Arg treatment. The above changes were accompanied with a rise in the number of dendritic cells (DCs) and an increase in their maturation. However, L-Arg did not affect the population of regulatory T cells or the level of IL-10 in the spleen. Taken together, these data suggest that L-Arg may enhance the Th1 immune response, which is essential for a protective response in uncomplicated malaria but could be lethal in CM patients. Therefore, the prophylactic use of L-Arg to treat CM, based on the assumption that restoring the bioavailability of endothelial NO improves the outcome of CM, may need to be reconsidered especially for children.

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“…Other authors have also demonstrated that the interruption of secretory organelles has antiparasitic effects (Udenya, 2004;Totino et al, 2008;Sturm et al, 2009). We have demonstrated that antiproliferative drugs that arrest intracellular development lead to protozoan death and elimination (Melo et al, 2000;Melo & Beiral, 2003;Tenorio et al, 2005;De Aquino et al, 2008).…”

Section: Discussionmentioning

confidence: 99%

“…Leaves of the Meliaceae species Azadirachta indica (neem) and Melia azedarach (cinnamon or Santa Barbara in Brazil) have been reported to exhibit immunomodulatory, anti-inflammatory, antihyperglycemic, anticarcinogenic, nematicidal, antiparasitic, antiviral, insecticidal and antioxidant properties (Khan et al, 2001;Salehzadeh et al, 2003;Wandscheera et al, 2004;Anthony et al, 2005). However, there is no knowledge about their biological action on intracellular Toxoplasma gondii.…”

Section: Introductionmentioning

confidence: 99%

Effects of aqueous leaf extracts of Azadirachta indica A. Juss. (neem) and Melia azedarach L. (Santa Barbara or cinnamon) on the intracellular development of Toxoplasma gondii

Melo

Vilela

Carvalho

2011

Rev. bras. plantas med.

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RESUMO: Efeito de extrato aquoso de folhas de Azadirachta indica A. Juss. (nim) e Melia azedarach L. (canela ou Santa Bárbara) sobre o desenvolvimento intracelular de Toxoplasma gondii. Melia azedarach (canela) e Azadirachta indica (nim) apresenta grande variedade de ingredientes biologicamente ativos contra vírus, bactérias e protozoários, mas nenhum efeito sobre o desenvolvimento intracelular do Toxoplasma gondii é conhecido. Toxoplasma gondii infecta todos os tipos de células Eucarióticas, onde se estabelece no meio intracelular em vacúolo modificado conhecido como vacúolo parasitóforo. Neste vacúolo ocorre a replicação levando a ruptura da célula hospedeira e reinfecção de novas células, perpetuando a infecção. A quimioterapia utilizada não é capaz de eliminar o parasita além de induzir fortes efeitos colaterais. Neste estudo, nós demonstramos o efeito in vitro de extratos aquosos da canela e nim sobre o desenvolvimento intracelular do taquizoíto do Toxoplasma gondii. Após tratamento de nim e canela por 24 h, a porcentagem de infecção e o número de taquizoítos intracelulares decaiu drasticamente. Este efeito foi concentração-dependente. Durante incubação dos extratos, uma progressiva desorganização morfológica e ultraestrutural levaram a formação de intensa vesiculação e completa destruição do parasita, que passou a uma estrutura amorfa, antes da completa eliminação do meio intracelular. No entanto durante o tratamento com os extratos, efeitos morfológicos não foram observados nas estruturas da célula hospedeira. Estes resultados sugerem que os extratos aquosos de nim e canela foram capazes de interferir e eliminar o desenvolvimento intracelular do Toxoplasma gondii. Palavras-chave: toxoplasma, nim, canela, citotoxicologiaABSTRACT: Melia azedarach (cinnamon) and Azadirachta indica (neem) have a variety of biologically active ingredients against virus, bacteria and protozoan parasites; however, little is known about their action on Toxoplasma gondii intracellular development. Toxoplasma gondii infects all eukaryotic cells, where it establishes and multiplies inside a modified vacuole called the parasitophorous vacuole until the cell ruptures, re-infecting other cells and establishing the infection. There are no efficient chemotherapies for the elimination of T. gondii, minimizing side effects. In this study, we performed in vitro assays with neem and cinnamon aqueous extracts against the intracellular development of T. gondii tachyzoites. After treatment with neem and cinnamon for 24 h, the percentage of infected cells and the number of intracellular parasites drastically decreased. This effect was concentration-dependent. During the incubation of the extracts, progressive morphological and ultrastructure alterations led to intense vesiculation and complete elimination of the parasite from the intracellular medium. However, during the treatment with extracts, no morphological effects were observed in the structure of the host cell. These results suggest that the aqueous extracts of neem and cinnamon were capa...

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Plasmodium falciparum: Erythrocytic stages die by autophagic-like cell death under drug pressure

Cited by 67 publications

References 40 publications

Borrelidin, a potent antimalarial: stage-specific inhibition profile of synchronized cultures of Plasmodium falciparum

Borrelidin, a potent antimalarial: stage-specific inhibition profile of synchronized cultures of Plasmodium falciparum

L-Arginine Exacerbates Experimental Cerebral Malaria by Enhancing Pro-Inflammatory Responses

Effects of aqueous leaf extracts of Azadirachta indica A. Juss. (neem) and Melia azedarach L. (Santa Barbara or cinnamon) on the intracellular development of Toxoplasma gondii

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