Bothrops moojeni Venom Kills Leishmania spp. with Hydrogen Peroxide Generated by Its -Amino Acid Oxidase

Tempone, André G.; Andrade, Heitor Franco de; Spencer, Patrick Jack; Lourenco, Corey; Rogero, J.R.; Nascimento, N.

doi:10.1006/bbrc.2000.4175

Cited by 111 publications

(84 citation statements)

References 29 publications

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“…(Tempone et al, 2001;Izidoro et al, 2006), Plasmodium falciparum (Zieler et al, 2001), and Trypanosoma cruzi (França et al, 2007). In the present study, we demonstrated for the first time the in vitro effects of a svLAAO isolated from Bothrops pirajai (BpirLAAO-I) on infection of T. gondii in human fibroblasts.…”

Section: Discussionsupporting

confidence: 62%

Bothrops pirajai snake venom L-amino acid oxidase: in vitro effects on infection of Toxoplasma gondii in human foreskin fibroblasts

Izidoro¹,

Alves²,

Rodrigues³

et al. 2011

Rev. bras. farmacogn.

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Abstract:The effect of an L-amino acid oxidase isolated from Bothrops pirajai snake venom (BpirLAAO-I) was investigated on infection of Toxoplasma gondii in human foreskin fibroblasts (HFF). The cytotoxic activity of BpirLAAO-I on HFF cells showed a dose-dependent toxicity with median cytotoxic dose (TD50) of 11.8 µg/mL. BpirLAAO-I induced considerable dose-dependent decrease in the T. gondii infection index under two different conditions, treatment of tachyzoites before infection or treatment of HFF cells after infection. A maximal inhibition of infection (56%) was found for treatment before infection, with a median inhibitory dose (ID50) at 1.83 µg/mL and selectivity index (SI) at 6.45. For treatment after infection, it was observed a maximal inhibition of infection at 65%, ID50 of 1.20 µg/mL and SI of 9.83. The treatment before infection was also effective to reduce intracellular parasitism up to 62%, although presenting higher values of ID50 (3.14 µg/mL) and lower values of SI (3.76). However, treatment after infection was not effective, suggesting that the enzyme seems to have no effect on the parasite intracellular replication for this condition. In conclusion, BpirLAAO-I was more effective to inhibit the infection of neighboring cells and consequently parasite dissemination than primary infection and parasite replication. Thus, the effect of BpirLAAO-I described herein could be taken into account for the development of new synthetic anti-parasite therapeutic agents.

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Section: Discussionsupporting

confidence: 62%

Bothrops pirajai snake venom L-amino acid oxidase: in vitro effects on infection of Toxoplasma gondii in human foreskin fibroblasts

Izidoro¹,

Alves²,

Rodrigues³

et al. 2011

Rev. bras. farmacogn.

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“…Venoms are a complex mixture with different biological effects, thus we can only speculate on the component(s) responsible for the induction of PCD in venom treated T. cruzi epimastigotes. However, Tempone et al (2001) have shown that the venom of Bothrops moojeni presents an L-amino acid oxidase responsible for growth inhibition of different Leishmania species. L-amino acid oxidase uses amino acids as substrate producing H 2 O 2 , which is a known inducer of PCD in metazoans (Hockenbery et al 1993, Clement & Pervaiz 1999 and also in unicellular organisms (Madeo et al 1999, Ridgley et al 1999, Mariante et al 2002.…”

Section: Discussionmentioning

confidence: 99%

Programmed cell death in Trypanosoma cruzi induced by Bothrops jararaca venom

Deolindo

Teixeira-Ferreira

Melo

et al. 2005

Mem. Inst. Oswaldo Cruz

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Cells die through a programmed process or accidental death, know as apoptosis or necrosis, respectively. Bothrops jararaca is a snake whose venom inhibits the growth ofIn multicellular organisms, programmed cell death (PCD), also known as apoptosis, is important to control cell number for proper development and tissue homeostasis, removal of unwanted cells and functional control of the immune, haemopoietic and nervous systems (Welburn et al. 1997). The process of PCD is activated by genetically controlled cell suicide machinery (Ameisen 1996). In vertebrate cells, PCD can be activated by external stimuli (ethanol, reactive oxygen species, and receptor ligands) and internal processes (mitotic catastrophe, replication failures, developmental programmed cell death) (Fröhlich & Madeo 2000). PCD is also a common response to cell stress caused by different toxins (Vaux 2002). Independent of the stimulus, PCD usually involves alteration in the mitochondrial membrane permeability, caspase activation, phosphatidylserine (PS) exposure, nuclear and cytoplasmic condensation, DNA fragmentation and breakage of the cell into apoptotic bodies, which are engulfed by the surrounding cells (Vaux & Strasser 1996). PCD is a process found in virtually all nucleated metazoan cells, and it has been recently associated with several species of unicellular eukaryotes, notably kinetoplastids (Ameisen et al. 1995, Welburn et al. 1996, Moreira et al. 1996 (Picot et al. 1997, Peng et al. 2003, and amitochondrion parasites (Chose et al. 2002, Mariante et al. 2003.Snake venoms have been identified as the richest source of enzymes among poisonous animal, displaying a variety of biological activities (Tan & Ponnudurai 1992). Bothrops jararaca is a snake of the viperidae family, largely distributed in Brazil and responsible for 90% of the ophidian envenomations in humans (Bochner & Struchiner 2003). Trypanosoma cruzi is the agent of Chagas disease affecting 16-18 million people in Latin America. We have previously demonstrated that B. jararaca venom inhibited the growth of epimastigote forms of T. cruzi, causing mitochondrion swelling and kinetoplast disorganization (Gonçalves et al. 2002). Because of the ultrastructural alteration observed in the mitochondrion after venom treatment it was suggested that impairment of this organelle was probably responsible for growth inhibition (Gonçalves et al. 2002). However, how epimastigotes were demising was not analyzed. Thus, the aim of the present work was to identify if PCD or necrosis was being induced in T. cruzi epimastigote forms during B. jararaca venom treatment. MATERIALS AND METHODSParasite and venom -Epimastigote forms of T. cruzi (Y strain) were maintained at 28°C by weekly transfers in liver infusion tryptose (LIT) medium (Camargo 1964) supplemented with 10% fetal bovine serum (FBS). Fourday-old cultured epimastigote forms (mid-log phase) were used for the experiments. 34 34 34 3 4 Cell death by snake venom • Poliana Deolindo et al.Lyophilized B. jararaca venom was purchased from the Instit...

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“…Diverse pharmacological activities have also been described for the crude venom of B. moojeni (BMV). For example, leishmanicidal activity (Castilhos et al, 2011), including a selective activity -a significant effect against promastigotes with no action on amastigotes forms (Tempone et al, 2001). BMV presented an antibacterial effect against Streptococcus mutans, the main etiological species of biofilms in dental caries (Mosca & Nascimento, 2011).…”

Section: Discussionmentioning

confidence: 99%

“…venoms have been shown to have antiparasitic activity, against Leishmania spp. (Tempone et al, 2001) and Trypanosoma cruzi (Deolindo et al, 2005); antimicrobial effects on Pseudomonas aeruginosa, Candida albicans, Escherichia coli, and Staphylococcus aureus (Ciscotto et al, 2009;Rodrigues et al, 2004;Torres et al, 2010); and inhibitory effect on in vitro invasion and replication of Toxoplasma gondii (Bastos et al, 2008).…”

Section: Introductionmentioning

confidence: 99%

In vitroandin vivogenotoxic evaluation ofBothrops moojenisnake venom

Zobiole

Caon

Bertól

et al. 2014

Pharmaceutical Biology

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Context: Bothrops moojeni Hoge (Viperidae) venom is a complex mixture of compounds with therapeutic potential that has been included in the research and development of new drugs. Along with the biological activity, the pharmaceutical applicability of this venom depends on its toxicological profile. Objective: This study evaluates the cytotoxicity and genotoxicity of the Bothrops moojeni venom (BMV). Material and methods: The in vitro cytotoxicity and genotoxicity of a pooled sample of BMV was assessed by the MTT and Comet assay, respectively. Genotoxicity was also evaluated in vivo through the micronucleus assay. Results: BMV displayed a 50% cytotoxic concentration (CC 50 ) on Vero cells of 4.09 mg/mL. Vero cells treated with 4 mg/mL for 90 min and 6 h presented significant (p50.05, ANOVA/NewmanKeuls test) higher DNA damage than the negative control in the Comet assay. The lower DNA damage found after 6 h compared with the 90 min treatment suggests a DNA repair effect. Mice intraperitoneally treated with BMV at 10, 30, or 80 mg/animal presented significant genotoxicity (p50.05, ANOVA/Newman-Keuls test) in relation to the negative control after 24 h of treatment. Contrary to the in vitro results, no DNA repair seemed to occur in vivo up to 96 h post-venom inoculation at a dose of 30 mg/animal. Discussion and conclusion: The results show that BMV presents cyto-and genotoxicity depending on the concentration/dose used. These findings emphasize the importance of toxicological studies, including assessment of genotoxicity, in the biological activity research of BMV and/or in the development of BMV-derived products.

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Bothrops moojeni Venom Kills Leishmania spp. with Hydrogen Peroxide Generated by Its -Amino Acid Oxidase

Cited by 111 publications

References 29 publications

Bothrops pirajai snake venom L-amino acid oxidase: in vitro effects on infection of Toxoplasma gondii in human foreskin fibroblasts

Bothrops pirajai snake venom L-amino acid oxidase: in vitro effects on infection of Toxoplasma gondii in human foreskin fibroblasts

Programmed cell death in Trypanosoma cruzi induced by Bothrops jararaca venom

In vitroandin vivogenotoxic evaluation ofBothrops moojenisnake venom

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