Crotoxin from Crotalus durissus terrificus venom: In vitro cytotoxic activity of a heterodimeric phospholipase A2 on human cancer-derived cell lines

Muller, Silvana Pinotti; Silva, Viviane Aline Oliveira; Silvestrini, Ana Vitória Pupo; Macedo, Luana Henrique de; Caetano, Guilherme Ferreira; Reis, Rui Manuel; Mazzi, Maurício Ventura

doi:10.1016/j.toxicon.2018.10.306

Cited by 43 publications

(33 citation statements)

References 47 publications

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“…The yellowish venom of Crotalus durissus terrificus (South American rattlesnake) was purchased from Koemitã (Mococa, São Paulo, Brazil). CTX was isolated and purified from the Crotalus durissus terrificus venom through two steps of DEAE-Sepharose and Heparin Sepharose FF chromatography, and protein identification was performed in a Waters ® Q-Tof Premier™ Mass Spectrometer, nanoACQUITY UPLC™ system, using a silica-based C18 Atlantis™ column (Waters Corporation, Milford, MA, USA), as extensively described previously [36]. The purity of CTX was determined by 13% (w/v) SDS-PAGE in a Tris-glycine buffer of pH 8.3, for 120 min at 30 mA/100 V. The molecular mass was measured using the Carestream Molecular Imaging Software (Carestream Health Inc., Rochester, NY, USA) and at 5-40 kDa molecular weight calibration standards PageRuler Low Range Unstained Protein Ladder (Thermo Fisher Scientific, Waltham, MA, USA).…”

Section: Purification Of Crotoxinmentioning

confidence: 99%

Evaluation of the Effectiveness of Crotoxin as an Antiseptic against Candida spp. Biofilms

Canelli

Rodrigues

Góes

et al. 2020

Toxins

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The growing number of oral infections caused by the Candida species are becoming harder to treat as the commonly used antibiotics become less effective. This drawback has led to the search for alternative strategies of treatment, which include the use of antifungal molecules derived from natural products. Herein, crotoxin (CTX), the main toxin of Crotalus durissus terrificus venom, was challenged against Candida tropicalis (CBS94) and Candida dubliniensis (CBS7987) strains by in vitro antimicrobial susceptibility tests. Minimum inhibitory concentration (MIC), minimum fungicidal concentration (MFC), and inhibition of biofilm formation were evaluated after CTX treatment. In addition, CTX-induced cytotoxicity in HaCaT cells was assessed by MTT (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide) colorimetric assay. Native CTX showed a higher antimicrobial activity (MIC = 47 μg/mL) when compared to CTX-containing mouthwash (MIC = 750 μg/mL) and nystatin (MIC = 375 μg/mL). Candida spp biofilm formation was more sensitive to both CTX and CTX-containing mouthwash (IC100 = 12 μg/mL) when compared to nystatin (IC100 > 47 μg/mL). Moreover, significant membrane permeabilization at concentrations of 1.5 and 47 µg/mL was observed. Native CTX was less cytotoxic to HaCaT cells than CTX-containing mouthwash or nystatin between 24 and 48 h. These preliminary findings highlight the potential use of CTX in the treatment of oral candidiasis caused by resistant strains.

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Section: Purification Of Crotoxinmentioning

confidence: 99%

Evaluation of the Effectiveness of Crotoxin as an Antiseptic against Candida spp. Biofilms

Canelli

Rodrigues

Góes

et al. 2020

Toxins

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“…(2) the toxin has promising medicinal applications due to its anti-inflammatory, immunosuppressive, antitumor, and analgesic properties [84,[90][91][92]. The potential medicinal application of CTX, as demonstrated in phase I clinical trials against cancer [18,93], stresses the importance of analyzing the side effects of the toxin that may occur in possible cases of intoxication during its therapeutic use.…”

Section: Discussionmentioning

confidence: 99%

Crotoxin-Induced Mice Lung Impairment: Role of Nicotinic Acetylcholine Receptors and COX-Derived Prostanoids

et al. 2020

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Respiratory compromise in Crotalus durissus terrificus (C.d.t.) snakebite is an important pathological condition. Considering that crotoxin (CTX), a phospholipase A2 from C.d.t. venom, is the main component of the venom, the present work investigated the toxin effects on respiratory failure. Lung mechanics, morphology and soluble markers were evaluated from Swiss male mice, and mechanism determined using drugs/inhibitors of eicosanoids biosynthesis pathway and autonomic nervous system. Acute respiratory failure was observed, with an early phase (within 2 h) characterized by enhanced presence of eicosanoids, including prostaglandin E2, that accounted for the increased vascular permeability in the lung. The alterations of early phase were inhibited by indomethacin. The late phase (peaked 12 h) was marked by neutrophil infiltration, presence of pro-inflammatory cytokines/chemokines, and morphological alterations characterized by alveolar septal thickening and bronchoconstriction. In addition, lung mechanical function was impaired, with decreased lung compliance and inspiratory capacity. Hexamethonium, a nicotinic acetylcholine receptor antagonist, hampered late phase damages indicating that CTX-induced lung impairment could be associated with cholinergic transmission. The findings reported herein highlight the impact of CTX on respiratory compromise, and introduce the use of nicotinic blockers and prostanoids biosynthesis inhibitors as possible symptomatic therapy to Crotalus durissus terrificus snakebite.

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“…CTX exerted anticoagulant and profibrinolytic action in the presence of LPS, decreasing the levels of vWF and t-PA and increasing the levels of the proteins C and PAI-1, thereby representing a potential tool against the development of thrombosis [ 99 ]. The antitumor activity has also been reported against glioma (GAMG and HCB151), and pancreatic (PSN-1 and PANC-1) cancer cells showed greater sensitivity with IC50 of <0.5, 4.1, 0.7, and <0.5 μg/mL, respectively [ 100 ].…”

Section: Nanosystems and Nanocarriersmentioning

confidence: 99%

Nanobiotechnology with Therapeutically Relevant Macromolecules from Animal Venoms: Venoms, Toxins, and Antimicrobial Peptides

et al. 2022

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Some diseases of uncontrolled proliferation such as cancer, as well as infectious diseases, are the main cause of death in the world, and their causative agents have rapidly developed resistance to the various existing treatments, making them even more dangerous. Thereby, the discovery of new therapeutic agents is a challenge promoted by the World Health Organization (WHO). Biomacromolecules, isolated or synthesized from a natural template, have therapeutic properties which have not yet been fully studied, and represent an unexplored potential in the search for new drugs. These substances, starting from conglomerates of proteins and other substances such as animal venoms, or from minor substances such as bioactive peptides, help fight diseases or counteract harmful effects. The high effectiveness of these biomacromolecules makes them promising substances for obtaining new drugs; however, their low bioavailability or stability in biological systems is a challenge to be overcome in the coming years with the help of nanotechnology. The objective of this review article is to describe the relationship between the structure and function of biomacromolecules of animal origin that have applications already described using nanotechnology and targeted delivery.

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Crotoxin from Crotalus durissus terrificus venom: In vitro cytotoxic activity of a heterodimeric phospholipase A2 on human cancer-derived cell lines

Abstract: Crotoxin from Crotalus durissus terrificus venom: in vitro cytotoxic activity of a heterodimeric phospholipase A 2 on human cancer-derived cell lines

Cited by 43 publications

References 47 publications

Evaluation of the Effectiveness of Crotoxin as an Antiseptic against Candida spp. Biofilms

Evaluation of the Effectiveness of Crotoxin as an Antiseptic against Candida spp. Biofilms

Crotoxin-Induced Mice Lung Impairment: Role of Nicotinic Acetylcholine Receptors and COX-Derived Prostanoids

Nanobiotechnology with Therapeutically Relevant Macromolecules from Animal Venoms: Venoms, Toxins, and Antimicrobial Peptides

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