In vitro assessment of cytotoxic activities of Lachesis muta muta snake venom.
Envenomation by the bushmaster snake Lachesis muta muta is considered severe, characterized by local effects including necrosis, the main cause of permanent disability. However, cellular mechanisms related to cell death and tissue destruction, triggered by snake venoms, are poorly explored. The purp...
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ftdoajarticles:oai:doaj.org/article:1b7ccbb2b2fc461d940650430bf11fde 2023-05-15T15:11:49+02:00 In vitro assessment of cytotoxic activities of Lachesis muta muta snake venom. Stephanie Stransky Fernanda Costal-Oliveira Letícia Lopes-de-Souza Clara Guerra-Duarte Carlos Chávez-Olórtegui Vania Maria Martin Braga 2018-04-01T00:00:00Z https://doi.org/10.1371/journal.pntd.0006427 https://doaj.org/article/1b7ccbb2b2fc461d940650430bf11fde EN eng Public Library of Science (PLoS) https://doi.org/10.1371/journal.pntd.0006427 https://doaj.org/toc/1935-2727 https://doaj.org/toc/1935-2735 1935-2727 1935-2735 doi:10.1371/journal.pntd.0006427 https://doaj.org/article/1b7ccbb2b2fc461d940650430bf11fde PLoS Neglected Tropical Diseases, Vol 12, Iss 4, p e0006427 (2018) Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 article 2018 ftdoajarticles https://doi.org/10.1371/journal.pntd.0006427 2022-12-31T04:02:48Z Envenomation by the bushmaster snake Lachesis muta muta is considered severe, characterized by local effects including necrosis, the main cause of permanent disability. However, cellular mechanisms related to cell death and tissue destruction, triggered by snake venoms, are poorly explored. The purpose of this study was to investigate the cytotoxic effect caused by L. m. muta venom in normal human keratinocytes and to identify the cellular processes involved in in cellulo envenomation. In order to investigate venom effect on different cell types, Alamar Blue assay was performed to quantify levels of cellular metabolism as a readout of cell viability. Apoptosis, necrosis and changes in mitochondrial membrane potential were evaluated by flow cytometry, while induction of autophagy was assessed by expression of GFP-LC3 and analyzed using fluorescence microscopy. The cytotoxic potential of the venom is shown by reduced cell viability in a concentration-dependent manner. It was also observed the sequential appearance of cells undergoing autophagy (by 6 hours), apoptosis and necrosis (12 and 24 hours). Morphologically, incubation with L. m. muta venom led to a significant cellular retraction and formation of cellular aggregates. These results indicate that L. m. muta venom is cytotoxic to normal human keratinocytes and other cell lines, and this toxicity involves the integration of distinct modes of cell death. Autophagy as a cell death mechanism, in addition to apoptosis and necrosis, can help to unravel cellular pathways and mechanisms triggered by the venom. Understanding the mechanisms that underlie cellular damage and tissue destruction will be useful in the development of alternative therapies against snakebites. Article in Journal/Newspaper Arctic Directory of Open Access Journals: DOAJ Articles Arctic PLOS Neglected Tropical Diseases 12 4 e0006427 |
institution |
Open Polar |
collection |
Directory of Open Access Journals: DOAJ Articles |
op_collection_id |
ftdoajarticles |
language |
English |
topic |
Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 |
spellingShingle |
Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 Stephanie Stransky Fernanda Costal-Oliveira Letícia Lopes-de-Souza Clara Guerra-Duarte Carlos Chávez-Olórtegui Vania Maria Martin Braga In vitro assessment of cytotoxic activities of Lachesis muta muta snake venom. |
topic_facet |
Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 |
description |
Envenomation by the bushmaster snake Lachesis muta muta is considered severe, characterized by local effects including necrosis, the main cause of permanent disability. However, cellular mechanisms related to cell death and tissue destruction, triggered by snake venoms, are poorly explored. The purpose of this study was to investigate the cytotoxic effect caused by L. m. muta venom in normal human keratinocytes and to identify the cellular processes involved in in cellulo envenomation. In order to investigate venom effect on different cell types, Alamar Blue assay was performed to quantify levels of cellular metabolism as a readout of cell viability. Apoptosis, necrosis and changes in mitochondrial membrane potential were evaluated by flow cytometry, while induction of autophagy was assessed by expression of GFP-LC3 and analyzed using fluorescence microscopy. The cytotoxic potential of the venom is shown by reduced cell viability in a concentration-dependent manner. It was also observed the sequential appearance of cells undergoing autophagy (by 6 hours), apoptosis and necrosis (12 and 24 hours). Morphologically, incubation with L. m. muta venom led to a significant cellular retraction and formation of cellular aggregates. These results indicate that L. m. muta venom is cytotoxic to normal human keratinocytes and other cell lines, and this toxicity involves the integration of distinct modes of cell death. Autophagy as a cell death mechanism, in addition to apoptosis and necrosis, can help to unravel cellular pathways and mechanisms triggered by the venom. Understanding the mechanisms that underlie cellular damage and tissue destruction will be useful in the development of alternative therapies against snakebites. |
format |
Article in Journal/Newspaper |
author |
Stephanie Stransky Fernanda Costal-Oliveira Letícia Lopes-de-Souza Clara Guerra-Duarte Carlos Chávez-Olórtegui Vania Maria Martin Braga |
author_facet |
Stephanie Stransky Fernanda Costal-Oliveira Letícia Lopes-de-Souza Clara Guerra-Duarte Carlos Chávez-Olórtegui Vania Maria Martin Braga |
author_sort |
Stephanie Stransky |
title |
In vitro assessment of cytotoxic activities of Lachesis muta muta snake venom. |
title_short |
In vitro assessment of cytotoxic activities of Lachesis muta muta snake venom. |
title_full |
In vitro assessment of cytotoxic activities of Lachesis muta muta snake venom. |
title_fullStr |
In vitro assessment of cytotoxic activities of Lachesis muta muta snake venom. |
title_full_unstemmed |
In vitro assessment of cytotoxic activities of Lachesis muta muta snake venom. |
title_sort |
in vitro assessment of cytotoxic activities of lachesis muta muta snake venom. |
publisher |
Public Library of Science (PLoS) |
publishDate |
2018 |
url |
https://doi.org/10.1371/journal.pntd.0006427 https://doaj.org/article/1b7ccbb2b2fc461d940650430bf11fde |
geographic |
Arctic |
geographic_facet |
Arctic |
genre |
Arctic |
genre_facet |
Arctic |
op_source |
PLoS Neglected Tropical Diseases, Vol 12, Iss 4, p e0006427 (2018) |
op_relation |
https://doi.org/10.1371/journal.pntd.0006427 https://doaj.org/toc/1935-2727 https://doaj.org/toc/1935-2735 1935-2727 1935-2735 doi:10.1371/journal.pntd.0006427 https://doaj.org/article/1b7ccbb2b2fc461d940650430bf11fde |
op_doi |
https://doi.org/10.1371/journal.pntd.0006427 |
container_title |
PLOS Neglected Tropical Diseases |
container_volume |
12 |
container_issue |
4 |
container_start_page |
e0006427 |
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1766342603518771200 |