Bothropoides insularis venom cytotoxicity in renal tubular epithelia cells

Mello, Clarissa Perdigão; Morais, Isabel Cristina Oliveira de; Menezes, Ramon Róseo Paula Pessoa Bezerra de; Pereira, Gustavo J.S.; Torres, Alba; Lima, Dânya Bandeira; Pereira, Ticiana Praciano; Toyama, Marcos H.; Monteiro, Helena Serra Azul; Smaili, Soraya Soubhi; Martins, Alice Maria Costa

doi:10.1016/j.toxicon.2014.05.009

Cited by 17 publications

(14 citation statements)

References 28 publications

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“…Apoptosis caused by snake venoms is mediated by various different components, such as metalloprotease, phospholipase A2 and L-amino acid oxidase [4][5][6][7][8]. Several studies have confirmed the involvement of Bothrops and Bothropoides venom components in apoptosis [9,10]. BpV (7.5 µg/mL) caused a left dislocation in TMRE fluorescence after 12 hrs of treatment (Figure 2A).…”

Section: Resultsmentioning

confidence: 90%

“…B. alternatus [12], B. insularis [10] and B. leucurus [9] also showed caspases 3/7 activation in MDCK cells. …”

Section: Resultsmentioning

confidence: 91%

“…BpV (7.5 µg/mL) caused a left dislocation in TMRE fluorescence after 12 hrs of treatment (Figure 2A). It is believed that the loss of mitochondrial transmembrane potential is due to the opening of the permeability transition pore, a mitochondrial mega channel, which is strongly affected by oxidative stress conditions [10].…”

Section: Resultsmentioning

confidence: 99%

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Cytotoxicity of Bothrops pauloensis Venom on Madin-Darby Canine Kidney Cells: Cell Death Mechanism

Ad¹,

Ico²,

Db³

et al. 2017

J Kidney

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Bothrops is a genus of pit vipers (snakes) endemic to Central and South America. Snake envenomation (Bothrops genus) specifically Bothropoides pauloensis, a venomous snake popularly known as "Jararaca pintada", which is found in the Brazilian territory or more commonly in the southwest of the state of Sao Paulois. Acute kidney injury is one of the complications observed in Bothrops snakebite with relevant morbidity and mortality. Here, we showed the cytotoxic effect of Bothropoides pauloensis venom on MDCK cells, intracellular mitochondrial membrane potentiality (ΔΨm), BpV regulated Reactive Oxygen Species (ROS) and activation of caspases 3 and 7 in MDCK cells. MDCK cells were treated with different concentrations of B. pauloensis venom for 24 hrs and cell death were measured with annexin V and PI staining and detected by flow cytometry. MDCK cells were treated with two different concentrations (IC50 and 2 × IC50) of BpV after 24 hrs. All data are expressed as mean ± SEM of three independent experiments with six replicates (ANOVA and Dunnett test, *p<0.05). Cytotoxicity was assessed by MTT assay and the treatment with BpV caused decrease in cell viability, with an IC50 of 7.5 µg/mL. After the treatment, amounts of ROS in the BpV-treated MDCK-cells (7.5 µg/mL) showed significant right dislocation of the fluorescence peak in the histogram, when compared with the untreated control group. Caspase 3 and 7 activity was determined in presence of the fluorogenic Ac-DEVDafc substrate after treatment with Bothropoides pauloensis venom (12 hrs) then the result indicated apoptotic involvement in BpV-induced cell death. Similar results were also found for venoms of other Bothrops and Bothropoides genus snakes such as B. alternatus, B. insularis and B. leucurus.

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Section: Resultsmentioning

confidence: 90%

“…B. alternatus [12], B. insularis [10] and B. leucurus [9] also showed caspases 3/7 activation in MDCK cells. …”

Section: Resultsmentioning

confidence: 91%

See 1 more Smart Citation

Cytotoxicity of Bothrops pauloensis Venom on Madin-Darby Canine Kidney Cells: Cell Death Mechanism

Ad¹,

Ico²,

Db³

et al. 2017

J Kidney

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“…AKI has been described in injury by toxins from a variety of animals (Sitprija and Sitprija, 2012). The nephrotoxicity of B. insularis venom has been previously described by our group (Braga et al, 2006;Mello et al, 2014), but in vivo studies have not been performed. In this study, we evaluated the nephrotoxic effect of this venom in mice through histological analyses, determination of TBARS and GSH levels.…”

Section: Resultsmentioning

confidence: 99%

“…The ectodomain is heavily glycosylated and stable and appears in the urine after the injury (Bonventre, 2014). B. insularis venom has been reported and characterized by its nephrotoxic effects on renal distal tubular epithelial cells (Mello et al, 2014) and kidney in situ (Braga et al, 2006(Braga et al, , 2007(Braga et al, , 2008. The nephrotoxicity caused by Bothrops venom in vivo was evaluated in this study, as well as the cytotoxicity in renal proximal tubular epithelial cells, aiming to evaluate KIM-1 as an early biomarker of snakebite-induced AKI in mice.…”

Section: Introductionmentioning

confidence: 99%

Evaluation of KIM-1 as an early biomarker of snakebite-induced AKI in mice

Dantas

Sampaio

Lima

et al. 2018

Toxicon

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Acute kidney injury (AKI) is one of the most important complications of bothropic poisoning and its early identification remains challenging. The nephrotoxicity of Bothrops insularis venom (BinsV) was previously described by our research group. In this study, we continued to evaluate the effect of BinsV on kidney function in mice and LLC-MK2 proximal tubule cells, evaluating KIM-1 protein as an early AKI biomarker. Male Swiss mice were inoculated with BinsV intramuscularly and observed for 24 h in a metabolic cage model. Urine and blood were collected for biochemical analyses and the kidneys were examined for oxide-reducing balance and submitted to histological analysis. LLC-MK2 cells incubated with BinsV were assessed for cell viability and cell death mechanism by flow cytometry. Histological analysis of the kidneys indicated AKI and the oxide-reducing analyses demonstrated a decreasing in reduced glutathione (GSH) levels and an increasing on Malondialdehyde (MDA) levels. BinsV was cytotoxic to LLC-MK2 and the cytometry analyses suggested necrosis. Within 24 h after the envenomation, urinary creatinine did not increase, but the urinary levels of KIM-1 increased. In conclusion, we found AKI evidence in the kidney tissue and the increase in the KIM-1 levels suggest it can be used as an early AKI biomarker.

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Acute kidney injury due to tropical infectious diseases and animal venoms: a tale of 2 continents

Burdmann

Jha

2017

Kidney International

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South and Southeast Asia and Latin American together comprise 46 countries and are home to approximately 40% of the world population. The sociopolitical and economic heterogeneity, tropical climate, and malady transitions characteristic of the region strongly influence disease behavior and health care delivery. Acute kidney injury epidemiology mirrors these inequalities. In addition to hospital-acquired acute kidney injury in tertiary care centers, these countries face a large preventable burden of community-acquired acute kidney injury secondary to tropical infectious diseases or animal venoms, affecting previously healthy young individuals. This article reviews the epidemiology, clinical picture, prevention, risk factors, and pathophysiology of acute kidney injury associated with tropical diseases (malaria, dengue, leptospirosis, scrub typhus, and yellow fever) and animal venom (snakes, bees, caterpillars, spiders, and scorpions) in tropical regions of Asia and Latin America, and discusses the potential future challenges due to emerging issues.

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Bothropoides insularis venom cytotoxicity in renal tubular epithelia cells

Cited by 17 publications

References 28 publications

Cytotoxicity of Bothrops pauloensis Venom on Madin-Darby Canine Kidney Cells: Cell Death Mechanism

Cytotoxicity of Bothrops pauloensis Venom on Madin-Darby Canine Kidney Cells: Cell Death Mechanism

Evaluation of KIM-1 as an early biomarker of snakebite-induced AKI in mice

Acute kidney injury due to tropical infectious diseases and animal venoms: a tale of 2 continents

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