Phoneutria nigriventer Venom and Toxins: A Review

Lima, Maria Elena de; Figueiredo, Suely G.; Matavel, Alessandra; Nunes, Kênia Pedrosa; Silva, Carolina Nunes da; Almeida, Flávia De Marco; Diniz, Marcelo R.V.; Cordeiro, Marta N.; Stankiewicz, Maria; Beirão, Paulo Sérgio Lacerda

doi:10.1007/978-94-007-6646-4_6-1

Cited by 18 publications

(33 citation statements)

References 61 publications

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“…Particularly, the venom of the Brazilian armed spider Phoneutria nigriventer contains a large range of peptide toxins, which have several activities in biological systems. Toxins from this venom have been described to be acting on many different targets, such as sodium, calcium and potassium voltage‐gated ion channels (Matavel et al , ; de Lima et al , ; Silva et al , ). Some of these toxins are also able to induce an increase in vascular permeability (Marangoni et al , ) and potentiate penile erection (Nunes et al , ) Furthermore, other venom components can inhibit glutamate uptake by brain synaptosomes (Mafra et al , ), while others inhibit NMDA‐evoked currents in rat hippocampal neurons (Figueiredo et al , ).…”

Section: Introductionmentioning

confidence: 99%

PnPP‐19, a spider toxin peptide, induces peripheral antinociception through opioid and cannabinoid receptors and inhibition of neutral endopeptidase

Freitas

Pacheco

Machado

et al. 2016

British J Pharmacology

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Background and Purpose The synthetic peptide PnPP‐19 has been studied as a new drug candidate to treat erectile dysfunction. However, PnTx2–6, the spider toxin from which the peptide was designed, induces hyperalgesia. Therefore, we intended to investigate the role of PnPP‐19 in the nociceptive pathway. Experimental Approach Nociceptive thresholds were measured by paw pressure test. PnPP‐19 was administered intraplantarly alone or with selective cannabinoid or opioid receptor antagonists. The hydrolysis of PnPP‐19 by neutral endopeptidase (NEP) (EC 3.4.24.11), an enzyme that cleaves enkephalin, was monitored by HPLC and the cleavage sites were deduced by LC–MS. Inhibition by PnPP‐19 and Leu‐enkephalin of NEP enzyme activity was determined spectrofluorimetrically. Key Results PnPP‐19 (5, 10 and 20 μg per paw) induced peripheral antinociception in rats. Specific antagonists of μ opioid receptors (clocinnamox), δ opioid receptors (naltrindole) and CB1 receptors (AM251) partly inhibited the antinociceptive effect of PnPP‐19. Inhibition of fatty acid amide hydrolase by MAFP or of anandamide uptake by VDM11 enhanced PnPP‐19‐induced antinociception. NEP cleaved PnPP‐19 only after a long incubation, and Ki values of 35.6 ± 1.4 and 14.6 ± 0.44 μmol·L−1 were determined for PnPP‐19 and Leu‐enkephalin respectively as inhibitors of NEP activity. Conclusions and Implications Antinociception induced by PnPP‐19 appears to involve the inhibition of NEP and activation of CB1, μ and δ opioid receptors. Our data provide a greater understanding of the antinociceptive effects of PnPP‐19. This peptide could be useful as a new antinociceptive drug candidate.

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Section: Introductionmentioning

confidence: 99%

PnPP‐19, a spider toxin peptide, induces peripheral antinociception through opioid and cannabinoid receptors and inhibition of neutral endopeptidase

Freitas

Pacheco

Machado

et al. 2016

British J Pharmacology

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“…Astrocytes are key protagonists to maintain brain homeostasis, which involves the reuptake of both extracellular K + and excitatory amino acids and Ca 2+ balance after neuronal activity. PNV contains neurotoxins that activate or delay inactivation of Na + and block Ca 2+ and K + channels and interfere in glutamate handling (see [6] for review). Further studies are necessary to determine the potential role of each subfield in the regulation of water metabolism.…”

Section: Discussionmentioning

confidence: 99%

“…In this study, the Cav-1 immunoreactivity of pyramidal neurons of CA hippocampal subfields is documental for the role of the protein also in neuronal cells function; PNV seemed to enhance the protein labeling (compare the intensity of Cav-1 labeling of pyramidal neurons pictured in Figure 3C (control) and Figure 3D (PNV-treated)). In hippocampal neurons, there is indication that induction of Cav-1 is triggered through glutamate exposure, apparently through kainate and AMPA-type receptors [50], receptors that are involved in hypernociception caused by PNV [6,7,51,52]. …”

Section: Discussionmentioning

confidence: 99%

“…The P. nigriventer venom (PNV) produces important excitatory effects [2,3] and its mechanism of action indicates the nervous system a key target. A plethora of neurotoxic peptides contained in the venom shows activity on Na + , K + and Ca 2+ channels and chemical receptors of excitable membranes of insects and mammals ([4,5], see [6] for review). It is known that altered homeostasis in ion movements in the nervous tissue compartments underlies neuronal dysfunction and a number of pathologies of the nervous system.…”

Section: Introductionmentioning

confidence: 99%

“…It is known that altered homeostasis in ion movements in the nervous tissue compartments underlies neuronal dysfunction and a number of pathologies of the nervous system. Thereupon, a great therapeutic interest motivates the abundant number of physiological and pharmacological studies involving PNV aiming at the development of new drugs [6,7]. …”

Section: Introductionmentioning

confidence: 99%

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Age-Related Modulations of AQP4 and Caveolin-1 in the Hippocampus Predispose the Toxic Effect of Phoneutria nigriventer Spider Venom

Soares

Stávale

Mendonça

et al. 2016

IJMS

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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. Western blotting protein levels; immunohistochemistry (IHC) protein distribution in CA1, CA2, and CA3 subfields; and gene expression by Real Time-Polymerase Chain Reaction (qPCR) were assessed in post-natal Day 14 (P14) and 8–10-week-old rats over critical periods of envenomation. The intensity and duration of the toxic manifestations indicate P14 neonate rats more vulnerable to PNV than adults. Histologically, the capillaries of P14 and 8–10-week-old rats treated with PNV showed perivascular edema, while controls did not. The intensity of the toxic manifestations in P14 decreases temporally (2 > 5 > 24 h), while inversely the expression of AQP4 and Cav-1 peaked at 24 h when clinically PNV-treated animals do not differ from saline controls. IHC of AQP4 revealed that hippocampal CA1 showed the least expression at 2 h when toxic manifestation was maximal. Subfield IHC quantification revealed that in P14 rats Cav-1 peaked at 24 h when toxic manifestations were absent, whereas in 8–10-week-old rats Cav-1 peaked at 2 h when toxic signs were highest, and progressively attenuated such increases until 24 h, remaining though significantly above baseline. Considering astrocyte-endothelial physical and functional interactions, we hypothesize that age-related modulations of AQP4 and Cav-1 might be linked both to changes in functional properties of astrocytes during post-natal development and in the BBB breakdown induced by the venom of P. nigriventer.

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Envenomation by Wandering Spiders (Genus Phoneutria)

Bucaretchi¹,

Bertani²,

Capitani³

et al. 2017

Toxinology

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Spiders of the genus Phoneutria, commonly known as wandering or banana spiders, are found in southern Central America (Costa Rica) and throughout South America east of the Andes into northern Argentina. Eight species, classified as Amazonian (P. fera, P. reidyi, and P. boliviensis) and non-Amazonian (P. keyserlingi, P. pertyi, P. eickstedtae, P. bahiensis, and P. nigriventer), have been described. Most of the clinically important bites by this genus occur in Brazil (~4,000 cases per year), with only 0.5% being severe. Local pain is the major symptom reported after most bites and involves peripheral (tachykinin (neurokinin NK 1 and NK 2) and glutamate receptors) and central (spinal) mechanisms (neurokinins, excitatory amino acids, nitric oxide, proinflammatory cytokines, and prostanoids). Other local features observed in envenomed patients include edema, erythema, radiating pain, sweating, fasciculation, and paresthesia. Systemic manifestations are less common and may include diaphoresis, tachycardia, arterial hypertension, agitation, prostration, sialorrhea, vomiting, tachypnea, pallor, hypothermia, cyanosis, diarrhea, and priapism. Shock and pulmonary edema, the main severe complications, are uncommon and possibly related to increased sympathetic activity and a systemic inflammatory response, although no sequential serum catecholamine, nitric oxide, and interleukin levels have been measured in prospective case series of human envenomations by Phoneutria spp. Most cases are treated symptomatically, with antivenom being recommended only for patients who develop important systemic clinical manifestations; such manifestations occur in~3% of cases and involve mainly children <10 years old and adults >70 years old. Fifteen deaths attributed to Phoneutria spp. have been reported in Brazil since 1903, but in only two of these cases are there sufficient details to confirm a causal nexus.

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Phoneutria nigriventer Venom and Toxins: A Review

Cited by 18 publications

References 61 publications

PnPP‐19, a spider toxin peptide, induces peripheral antinociception through opioid and cannabinoid receptors and inhibition of neutral endopeptidase

PnPP‐19, a spider toxin peptide, induces peripheral antinociception through opioid and cannabinoid receptors and inhibition of neutral endopeptidase

Age-Related Modulations of AQP4 and Caveolin-1 in the Hippocampus Predispose the Toxic Effect of Phoneutria nigriventer Spider Venom

Envenomation by Wandering Spiders (Genus Phoneutria)

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