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Rodrigo B M Silva, Samuel Greggio, Gianina T Venturin, Jaderson C da Costa, Marcus V Gomez, Maria M Campos
Voltage-gated calcium channels (VGCCs) play a critical role in neuroinflammatory diseases, such as multiple sclerosis (MS). CTK 01512-2 is a recombinant version of the peptide Phα1β derived from the spider Phoneutria nigriventer, which inhibits N-type VGCC/TRPA1-mediated calcium influx. We investigated the effects of this molecule in the mouse model of experimental autoimmune encephalomyelitis (EAE). The effects of CTK 01512-2 were compared to those displayed by ziconotide-a selective N-type VGCC blocker clinically used for chronic pain-and fingolimod-a drug employed for MS treatment...
April 17, 2018: Molecular Neurobiology
Kelly L Wormwood, Armand Gatien Ngounou Wetie, Marcus Vinicius Gomez, Yue Ju, Paul Kowalski, Marius Mihasan, Costel C Darie
Native Phα1β is a peptide purified from the venom of the armed spider Phoneutria nigriventer that has been shown to have an extensive analgesic effect with fewer side effects than ω-conotoxin MVIIA. Recombinant Phα1β mimics the effects of the native Phα1β. Because of this, it has been suggested that Phα1β may have potential to be used as a therapeutic for controlling persistent pathological pain. The amino acid sequence of Phα1β is known; however, the exact structure and disulfide arrangement has yet to be determined...
April 16, 2018: Journal of the American Society for Mass Spectrometry
Ana C N Freitas, Steve Peigneur, Flávio H P Macedo, José E Menezes-Filho, Paul Millns, Liciane F Medeiros, Maria A Arruda, Jader Cruz, Nicholas D Holliday, Jan Tytgat, Gareth Hathway, Maria E de Lima
The synthetic peptide PnPP-19 comprehends 19 amino acid residues and it represents part of the primary structure of the toxin δ-CNTX-Pn1c (PnTx2-6), isolated from the venom of the spider Phoneutria nigriventer. Behavioural tests suggest that PnPP-19 induces antinociception by activation of CB1, μ and δ opioid receptors. Since the peripheral and central antinociception induced by PnPP-19 involves opioid activation, the aim of this work was to identify whether this synthetic peptide could directly activate opioid receptors and investigate the subtype selectivity for μ-, δ- and/or κ-opioid receptors...
January 15, 2018: Toxins
Matheus Pires Rincão, João Lucas Chavari, Antonio Domingos Brescovit, Ana Lúcia Dias
The present study aimed to cytogenetically analyse five Ctenidae species Ctenus ornatus (Keyserling, 1877), Ctenus medius (Keyserling, 1891), Phoneutria nigriventer (Keyserling, 1891), Viracucha andicola (Simon, 1906), and Enoploctenus cyclothorax (Philip Bertkau, 1880), from Brazil. All species presented a 2n♂ = 28 except for V. andicola , which showed 2n♂ = 29. Analysis of segregation and behavior of sex chromosomes during male meiosis showed a sex chromosome system of the type X1 X2 0 in species with 28 chromosomes and X1 X2 X3 0 in V...
2017: Comparative Cytogenetics
Flavia Karine Rigo, Mateus Fortes Rossato, Gabriela Trevisan, Samira Dal-Toé De Prá, Rafael Porto Ineu, Mariane Bernardo Duarte, Célio José de Castro Junior, Juliano Ferreira, Marcus Vinicius Gomez
BACKGROUND AND AIMS: Cholinergic agents cause antinociception by mimicking the release of acetylcholine (ACh) from spinal cholinergic nerves. PhKv is a peptide isolated from the venom of the armed spider Phoneutria nigriventer. It has an antiarrythmogenic activity that involves the enhanced release of acetylcholine. The aim of this study was to investigate whether PhKv had an antinociceptive action in mice. METHODS: Male albino Swiss mice (25-35g) were used in this study...
October 26, 2017: Scandinavian Journal of Pain
Katherine Garcia Ravelli, Adriana de Toledo Ramos, Luana Baracho Gonçalves, Fábio Carlos Magnoli, Lanfranco Ranieri Paolo Troncone
The Phoneutria nigriventer spider toxin Tx2-6 causes priapism in humans and mice. This toxin produces a delay in Sodium channel inactivation, generalized vascular congestion and death by respiratory failure. NO-Synthase inhibitors seem to abolish toxin-induced priapism. The understanding of the ultimate molecular mechanism involved in toxin-induced priapism may shed light on aspects of erectile function/dysfunction. This study investigates if cavernosal denervation can abolish the toxin-induced priapism. Surgical cavernosal nerve excision/denervation was performed in mice and confirmed by infertility, histological assessment of fibrosis and immunohistochemical staining for synaptophysin...
May 2017: Toxicon: Official Journal of the International Society on Toxinology
Edilene S Soares, Leila M Stávale, Monique C P Mendonça, Andressa Coope, Maria Alice da Cruz-Höfling
We have previously demonstrated that Phoneutria nigriventer venom (PNV) causes blood-brain barrier (BBB) breakdown, swelling of astrocytes end-feet and fluid permeation into brain interstitium in rats. Caveolae and water channels respond to BBB alterations by co-participation in shear stress response and edema formation/resolution. Herein, we showed post-natal developmental-related changes of two BBB-associated transporter proteins: the endothelial caveolin-1 (Cav-1), the major scaffolding protein from caveolae frame, and the astroglial aquaporin-4 (AQP4), the main water channel protein expressed in astrocytic peri-vascular end-feet processes, in the hippocampus of rats intraperitoneally-administered PNV...
November 23, 2016: International Journal of Molecular Sciences
Raquel Tonello, Camilla Fusi, Serena Materazzi, Ilaria M Marone, Francesco De Logu, Silvia Benemei, Muryel C Gonçalves, Elisabetta Coppi, Celio J Castro-Junior, Marcus Vinicius Gomez, Pierangelo Geppetti, Juliano Ferreira, Romina Nassini
BACKGROUND AND PURPOSE: Peptides from venomous animals have long been important for understanding pain mechanisms and for the discovery of pain treatments. Here, we hypothesized that Phα1β, a peptide from the venom of the armed spider Phoneutria nigriventer, produces analgesia by blocking the TRPA1 channel. EXPERIMENTAL APPROACH: Cultured rat dorsal root ganglion (DRG) neurons, human fetal lung fibroblasts (IMR90) or HEK293 cells expressing the human TRPA1 (hTRPA1-HEK293), human TRPV1 (hTRPV1-HEK293) or human TRPV4 channels (hTRPV4-HEK293), were used for calcium imaging and electrophysiology...
January 2017: British Journal of Pharmacology
Mahfouz Ahmad Al-Agroudi, Salwa Abdalla Mohammad Ahmed, Tosson A Morsy
Spider bites are uncommon medical events, since there are limited number of spiders world-wide with fangs strong enough to pierce human skin, and most spiders bite humans only as a final defense when being crushed between skin and another object. Thus, most lesions attributed to spider bites are caused by some other etiology. The spiders that can cause medically significant bites include widow and false widow spiders (worldwide), recluse spiders (mostly North and South America), Australian funnel web spiders (eastern coastal Australia) and Phoneutria spiders (Brazil)...
April 2016: Journal of the Egyptian Society of Parasitology
Catarina Rapôso, Ulrika Björklund, Evanguedes Kalapothakis, Björn Biber, Maria Alice da Cruz-Höfling, Elisabeth Hansson
Bites from genus Phoneutria (Ctenidae, Araneomorpha) are the second most frequent source of spider accidents in Southeast Brazil. Severe envenoming from Phoneutria nigriventer produces vision disturbance, tremor and convulsion, suggesting that the CNS is involved; however, the mechanisms by which P. nigriventer venom (PNV) affects the CNS remain poorly understood. The present study aimed to investigate whether PNV directly impairs astrocytes. Cultured astrocytes were exposed to PNV, and intracellular Ca(2+) release and signaling were measured (Fura-2/AM), Na(+)/K(+)-ATPase and Toll-like receptor 4 (TLR4) involvement were investigated, actin filaments were stained (Alexa™ 488-conjugated phalloidin probe), the G-actin/F-actin ratio was determined, and the expression level of connexin 43 (Cx43) was assessed...
June 2016: Neurochemistry International
Bruna Luiza Emerich, Renata C M Ferreira, Marta N Cordeiro, Márcia Helena Borges, Adriano M C Pimenta, Suely G Figueiredo, Igor Dimitri G Duarte, Maria Elena de Lima
PnTx4(6-1), henceforth renamed δ-Ctenitoxin-Pn1a (δ-CNTX-Pn1a), a peptide from Phoneutria nigriventer spider venom, initially described as an insect toxin, binds to site 3 of sodium channels in nerve cord synaptosomes and slows down sodium current inactivation in isolated axons in cockroaches (Periplaneta americana). δ-CNTX-Pn1a does not cause any apparent toxicity to mice, when intracerebroventricularly injected (30 μg). In this study, we evaluated the antinociceptive effect of δ-CNTX-Pn1a in three animal pain models and investigated its mechanism of action in acute pain...
April 12, 2016: Toxins
Edilene Siqueira Soares, Monique Culturato Padilha Mendonça, Thalita Rocha, Evanguedes Kalapothakis, Maria Alice da Cruz-Höfling
Upregulation of caveolin-3 (Cav-3) or connexin-43 (Cx43) in astrocytes has been associated with important brain pathologies. We used Phoneutria nigriventer spider venom (PNV), which induces blood-brain barrier breakdown in rats, in order to investigate Cav-3 and Cx43 expression in the cerebellum over critical periods of rat envenomation. By immunofluorescence, western blotting (WB), and transmission electron microscopy (TEM), we assessed changes at 1, 2, 5, 24, and 72 h post-venom. WB showed immediate increases in Cav-3 and Cx43 at 1 h (interval of greatest manifestations of envenomation) that persisted at 5 h (when there were signs of recovery) and peaked at 24 h when no signs of envenomation were detectable...
August 2016: Journal of Molecular Neuroscience: MN
Edilene Siqueira Soares, Monique Culturato Padilha Mendonça, Maria Alice da Cruz-Höfling
An important transcellular transport mechanism in the blood-brain barrier (BBB) involves caveolae, which are specialized delta-shaped domains of the endothelial plasma membrane that are rich in cholesterol, glycosphingolipids and the scaffolding protein Caveolina-1 (Cav-1). In this work, we investigated whether the increase in endocytosis and transendothelial vesicular trafficking in rat cerebellum after blood-brain barrier breakdown (BBBb) induced by Phoneutria nigriventer spider venom (PNV) was mediated by caveolae...
May 2016: Neurotoxicology
Sara M Oliveira, Cássia R Silva, Gabriela Trevisan, Jardel G Villarinho, Marta N Cordeiro, Michael Richardson, Márcia H Borges, Célio J Castro, Marcus V Gomez, Juliano Ferreira
The venom of the Brazilian armed spider Phoneutria nigriventer is a rich source of biologically active peptides that have potential as analgesic drugs. In this study, we investigated the analgesic and adverse effects of peptide 3-5 (Tx3-5), purified from P. nigriventer venom, in several mouse models of pain. Tx3-5 was administered by intrathecal injection to mice selected as models of postoperative (plantar incision), neuropathic (partial sciatic nerve ligation) and cancer-related pain (inoculation with melanoma cells) in animals that were either sensitive or tolerant to morphine...
May 2016: Pflügers Archiv: European Journal of Physiology
Tarcísio Liberato, Lanfranco Ranieri Paolo Troncone, Edson T Yamashiro, Solange M T Serrano, André Zelanis
Here we present a proteomic characterization of Phoneutria nigriventer venom. A shotgun proteomic approach allowed the identification, for the first time, of O-glycosyl hydrolases (chitinases) in P. nigriventer venom. The electrophoretic profiles under nonreducing and reducing conditions, and protein identification by mass spectrometry, indicated the presence of oligomeric toxin structures in the venom. Complementary proteomic approaches allowed for a qualitative and semi-quantitative profiling of P. nigriventer venom complexity, expanding its known venom proteome diversity...
March 2016: Amino Acids
Flavia R Silva, Edleusa M L Batista, Marcus V Gomez, Christopher Kushmerick, Juliana F Da Silva, Marta N Cordeiro, Luciene B Vieira, Fabiola M Ribeiro
Spider toxins are recognized as useful sources of bioactive substances, showing a wide range of pharmacological effects on neurotransmission. Several spider toxins have been identified biochemically and some of them are specific glutamate receptors antagonists. Previous data indicate that PnTx4-5-5, a toxin isolated from the spider Phoneutria nigriventer, inhibits the N-methyl-d-aspartate receptor (NMDAR), with little or no effect on AMPA, kainate or GABA receptors. In agreement with these results, our findings in this study show that PnTx4-5-5 reduces the amplitude of NMDAR-mediated EPSCs in hippocampal slices...
March 15, 2016: Toxicon: Official Journal of the International Society on Toxinology
Ana L B Paiva, Alessandra Matavel, Steve Peigneur, Marta N Cordeiro, Jan Tytgat, Marcelo R V Diniz, Maria Elena de Lima
The toxin PnTx4(5-5) from the spider Phoneutria nigriventer is extremely toxic/lethal to insects but has no macroscopic behavioral effects observed in mice after intracerebral injection. Nevertheless, it was demonstrated that it inhibits the N-methyl-d-aspartate (NMDA) - subtype of glutamate receptors of cultured rat hippocampal neurons. PnTx4(5-5) has 63% identity to PnTx4(6-1), another insecticidal toxin from P. nigriventer, which can slow down the sodium current inactivation in insect central nervous system, but has no effect on Nav1...
February 2016: Biochimie
Juliana Figueira da Silva, Célio José Castro-Junior, Sara Marchesan Oliveira, Gerusa Duarte Dalmolin, Cássia Regina Silva, Luciene Bruno Vieira, Danuza Montijo Diniz, Marta do Nascimento Cordeiro, Juliano Ferreira, Alessandra Hubner Souza, Marcus Vinícius Gomez
Venom-derived peptides constitute a unique source of drug prototypes for the pain management. Many of them can modulate voltage-gated calcium channels that are central in the processing of pain sensation. PhTx3-4 is a peptide isolated from Phoneutria nigriventer venom, which blocks high voltage-activated calcium channels with low specificity, thereby leading to neuroprotection in models of ischemia in vitro. The aim of the present work was evaluating the potential of intrathecal PhTx3-4 in the reversal of different nociceptive states in mice, furthermore assessing the potential of PhTx3-4 in triggering motor side effects...
December 15, 2015: Toxicon: Official Journal of the International Society on Toxinology
Richard S Vetter, Rodney L Crawford, Donald J Buckle
Spiders found in international cargo brought into North America are sometimes submitted to arachnologists for identification. Often, these spiders are presumed to be of medical importance because of size or a submitter's familiarity with a toxic spider genus from the continent of origin. Starting in 2006, requests were made for spiders found in international cargo brought into North America, in addition to the specimens from similar cargo shipments already in our museum collections. This was an ad hoc study that allowed us to focus on spiders of concern to the discoverer...
November 1, 2014: Journal of Medical Entomology
Sebastian Estrada-Gomez, Leidy Johana Vargas Muñoz, Paula Lanchero, Cesar Segura Latorre
We report on the first studies on the characterization of venom from Phoneutria boliviensis (Aranae:Ctenidae) (F. O. Pickard-Cambridge, 1897), done with Colombian species. After the electrostimulation extraction process, the venom showed physicochemical properties corresponding to a colorless and water-soluble liquid with a density of 0.86 mg/mL and 87% aqueous content. P. boliviensis venom and RP-HPLC fractions showed hemolytic activity and hydrolyzed the synthetic substrate 4-nitro-3-octanoyloxy-benzoic acid, indicating the presence of phospholipases A2 enzymes...
August 2015: Toxins
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