The toxin BjussuLAAO-II induces oxidative stress and DNA damage, upregulates the inflammatory cytokine genes TNF and IL6, and downregulates the apoptotic-related genes BAX, BCL2 and RELA in human Caco-2 cells

Machado, Ana Rita Thomazela; Aissa, Alexandre Ferro; Ribeiro, Diego Luís; Hernandes, Lívia Cristina; Machado, Cerilene Santiago; Bianchi, Marcelo; Sampaio, Suely Vilela; Antunes, L.M.G.

doi:10.1016/j.ijbiomac.2017.12.015

Cited by 19 publications

(12 citation statements)

References 47 publications

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“…The increase in TNF expression was to be expected, considering high levels of TNF-α have been observed in numerous experiments involving snake venoms. These experiments used either crude snake venoms [ 11 , 35 , 36 , 40 , 43 ] or isolated snake venom proteins, including SVMPs [ 19 , 20 , 57 ], svPLA 2 s [ 13 , 37 , 44 ], or LAAOs [ 23 , 58 ].…”

Section: Resultsmentioning

confidence: 99%

“…The release of hydrogen peroxide is linked to the apoptotic, cytotoxic, hemorrhagic, and edema inducing effect of LAAOs [ 8 , 21 ]. Furthermore, recent studies have demonstrated that administration of purified LAAOs induces the release of several proinflammatory mediators, such as IL-6, IL-8, TNF-α, PGE 2 , and leukotriene B4 (LTB 4 ) [ 22 , 23 , 24 ].…”

Section: Introductionmentioning

confidence: 99%

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Effect of Vipera ammodytes ammodytes Snake Venom on the Human Cytokine Network

Boda

Banfai

Garai

et al. 2018

Toxins

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Local inflammation is a well-known symptom of envenomation by snakes of the family Viperidae, attributed primarily to the phospholipase A2s, metalloproteinases and L-amino acid oxidases contained in their venom. The inflammatory effect of snake venoms has been associated with a marked increase of the cytokines IL-1β, IL-6, IL-8, IL-10 and TNF-α. To determine the impact of Vipera ammodytes ammodytes snake venom on the expression of inflammation-related genes, we incubated human U937 monocyte cells with dilutions of snake venom. Gene expression was quantified for 28 different genes using a TaqMan® Array Human Cytokine Network 96-well Plate in a RT-qPCR system. Our results have demonstrated that 1.0 μg/mL Vipera ammodytes ammodytes venom solution induces a notable change in the expression of several cytokine network genes. Among the upregulated genes, there were several that encode interleukins, interferons, and tumor necrosis factors. We further report the downregulation of three interleukin-related genes. Our findings come as supportive information for the known complex effect of snake venoms on the human cytokine network. It also provides relevant new information regarding the expression of genes that have not been previously associated with the effect of snake venoms.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Effect of Vipera ammodytes ammodytes Snake Venom on the Human Cytokine Network

Boda

Banfai

Garai

et al. 2018

Toxins

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“…Similar results are reported in the present study from BjussuLAAO-II since the toxin reduced the viability of the non-tumor HUVEC in the MTT assay. In a previous study, BjussuLAAO-II was tested against human colorectal adenocarcinoma cells (Caco-2) in a 24h treatment and also demonstrated the reduction of cell viability [34].…”

Section: Discussionmentioning

confidence: 99%

BjussuLAAO-II induces cytotoxicity and alters DNA methylation of cell-cycle genes in monocultured/co-cultured HepG2 cells

Machado

Aissa

Ribeiro

et al. 2019

J. Venom. Anim. Toxins incl. Trop. Dis

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Background: The use of animal venoms and their toxins as material sources for biotechnological applications has received much attention from the pharmaceutical industry. L-amino acid oxidases from snake venoms (SV-LAAOs) have demonstrated innumerous biological effects and pharmacological potential against different cancer types. Hepatocellular carcinoma has increased worldwide, and the aberrant DNA methylation of liver cells is a common mechanism to promote hepatic tumorigenesis. Moreover, tumor microenvironment plays a major role in neoplastic transformation. To elucidate the molecular mechanisms responsible for the cytotoxic effects of SV-LAAO in human cancer cells, this study aimed to evaluate the cytotoxicity and the alterations in DNA methylation profiler in the promoter regions of cell-cycle genes induced by BjussuLAAO-II, an LAAO from Bothrops jaracussu venom, in human hepatocellular carcinoma (HepG2) cells in monoculture and co-culture with endothelial (HUVEC) cells. Methods: BjussuLAAO-II concentrations were 0.25, 0.50, 1.00 and 5.00 μg/mL. Cell viability was assessed by MTT assay and DNA methylation of the promoter regions of 22 cell-cycle genes by EpiTect Methyl II PCR array. Results: BjussuLAAO-II decreased the cell viability of HepG2 cells in monoculture at all concentrations tested. In co-culture, 1.00 and 5.00 μg/mL induced cytotoxicity ( p < 0.05). BjussuLAAO-II increased the methylation of CCND1 and decreased the methylation of CDKN1A in monoculture and GADD45A in both cell-culture models ( p < 0.05). Conclusion: Data showed BjussuLAAO-II induced cytotoxicity and altered DNA methylation of the promoter regions of cell-cycle genes in HepG2 cells in monoculture and co-culture models. We suggested the analysis of DNA methylation profile of GADD45A as a potential biomarker of the cell cycle effects of BjussuLAAO-II in cancer cells. The tumor microenvironment should be considered to comprise part of biotechnological strategies during the development of snake-toxin-based novel drugs.

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“…The toxin BjussuLAAO-II from B. jararacussu induces oxidative stress and DNA damage and upregulates the inflammatory cytokine genes TNF and IL6, a potential anti-inflammatory effect for exploration [ 61 ].…”

Section: Introductionmentioning

confidence: 99%

Biomedical applications of snake venom: from basic science to autoimmunity and rheumatology

Cañas

Castaño-Valencia

Castro-Herrera

et al. 2021

Journal of Translational Autoimmunity

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Snake venoms have components with diverse biological actions that are extensively studied to identify elements that may be useful in biomedical sciences. In the field of autoimmunity and rheumatology, various findings useful for the study of diseases and potential drug development have been reported. The study of disintegrins, proteins that block the action of integrins, has been useful for the development of antiplatelet agents and principles for the development of immunosuppressants and antineoplastics. Several proteins in snake venoms act on the coagulation cascade, activating factors that have allowed the development of tests for the study of coagulation, including Russell’s viper venom time, which is useful in the diagnosis of antiphospholipid syndrome. Neurotoxins with either pre- or postsynaptic effects have been used to study neurogenic synapses and neuromuscular plaques and the development of analgesics, muscle relaxants and drugs for neurodegenerative diseases. Various components act by inhibiting cells and proteins of the immune system, which will allow the development of anti-inflammatory and immunosuppressive drugs. This review summarizes the usefulness of the components of snake venoms in the fields of autoimmunity and rheumatology, which can serve as a basis for diverse translational research.

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The toxin BjussuLAAO-II induces oxidative stress and DNA damage, upregulates the inflammatory cytokine genes TNF and IL6, and downregulates the apoptotic-related genes BAX, BCL2 and RELA in human Caco-2 cells

Cited by 19 publications

References 47 publications

Effect of Vipera ammodytes ammodytes Snake Venom on the Human Cytokine Network

Effect of Vipera ammodytes ammodytes Snake Venom on the Human Cytokine Network

BjussuLAAO-II induces cytotoxicity and alters DNA methylation of cell-cycle genes in monocultured/co-cultured HepG2 cells

Biomedical applications of snake venom: from basic science to autoimmunity and rheumatology

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