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Carolina Nunes da Silva
Faculty of Pharmacy, Federal University of Minas Gerais, Pampulha, Av. Antônio Carlos, 6627, Belo Horizonte, Minas Gerais, 31270-901, Brazil

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Journal article
Published: 26 November 2020 in Biomedicine & Pharmacotherapy
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Retinal ischemia, one of the most common cause of visual loss, is associated with blood flow inadequacy and subsequent tissue injury. In this setting, some treatments that can counteract glutamate increase, arouse interest in ischemic pathogenesis. Ketamine, a potent N-methyl-d-aspartate (NMDA) receptor antagonist, provides a neuroprotective pathway via decreasing the excitotoxicity triggered by excess glutamatergic. Thus, the goal of this study was to evaluate the safety of intravitreal use of ketamine and their potential protective effects on retinal cells in retinal ischemia/reperfusion model. Initially, ketamine toxicity was evaluated by cytotoxicity assay and Hen's egg chorioallantoic membrane (HET-CAM) method. Afterward, some ketamine concentrations were tested in rat's eyes to verify the safety of the intravitreal use. To investigate the neuroprotective effect on retinal, a single intravitreal injection of ketamine in concentrations of 0.059 mmol.L−1 and 0.118 mmol.L−1 was performed one day before the retinal injury by ischemia/reperfusion model. After 7 and 15 days, the retina activity was evaluated by electroretinogram (ERG) records and, lastly, by morphological analyzes. Cytotoxicity assay reveals that the maximum ketamine concentration that could reach retinal pigmented epithelium cells is 0.353 mmol.L−1. HET-CAM assay showed that concentrations above 0.237 mmol.L−1 are irritants to the eye. Thus, Ketamine in concentrations of 0.0237 mmol.L−1, 0.118 mmol.L-1, and 0.059 mmol.L-1 were selected for in vivo toxicity test. ERG records reveal a tendency of b-wave amplitude to decrease as the luminous intensity increased, in the group receiving ketamine at 0.237 mmol.L−1. Therefore, ketamine in concentrations at 0.059 mmol.L−1 and 0.118 mmol.L-1 were chosen for the following tests. In the ischemia retinal degeneration model, pretreatment with ketamine was capable to promote a recovery of retinal electrophysiological function minimizing the ischemic effects. In histological analysis, the groups that received intravitreal ketamine showed a number of retinal cells significantly higher than the vehicle group. In TUNEL assay a reduction on TUNEL-positive cells was observed in all the layers for both concentrations which allow to affirm that ketamine contributes to reducing cell death in the retina. Transmission electron microscopy (TEM) reaffirms this finding. Ketamine intravitreal pretreatment showed reduced ultrastructural changes. Our findings demonstrate that ketamine is safe for intravitreal use in doses up to 0.118 mmol.L−1. They seem to be particularly efficient to protect the retina from ischemic injury.

ACS Style

Lays Fernanda Nunes Dourado; Lucas Gomes Oliveira; Carolina Nunes da Silva; Cibele Rodrigues Toledo; Silvia Ligório Fialho; Rodrigo Jorge; Armando Silva-Cunha. Intravitreal ketamine promotes neuroprotection in rat eyes after experimental ischemia. Biomedicine & Pharmacotherapy 2020, 133, 110948 .

AMA Style

Lays Fernanda Nunes Dourado, Lucas Gomes Oliveira, Carolina Nunes da Silva, Cibele Rodrigues Toledo, Silvia Ligório Fialho, Rodrigo Jorge, Armando Silva-Cunha. Intravitreal ketamine promotes neuroprotection in rat eyes after experimental ischemia. Biomedicine & Pharmacotherapy. 2020; 133 ():110948.

Chicago/Turabian Style

Lays Fernanda Nunes Dourado; Lucas Gomes Oliveira; Carolina Nunes da Silva; Cibele Rodrigues Toledo; Silvia Ligório Fialho; Rodrigo Jorge; Armando Silva-Cunha. 2020. "Intravitreal ketamine promotes neuroprotection in rat eyes after experimental ischemia." Biomedicine & Pharmacotherapy 133, no. : 110948.

Conference abstract
Published: 19 June 2020 in Toxicon
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C.N. Silva; L.F.D. Dourado; M.E. De Lima; A. Silva Cunha. PNPP-19, A synthetic peptide designed from Phoneutria nigriventer spider toxin is effective for glaucoma treatment in rats. Toxicon 2020, 182, S23 .

AMA Style

C.N. Silva, L.F.D. Dourado, M.E. De Lima, A. Silva Cunha. PNPP-19, A synthetic peptide designed from Phoneutria nigriventer spider toxin is effective for glaucoma treatment in rats. Toxicon. 2020; 182 ():S23.

Chicago/Turabian Style

C.N. Silva; L.F.D. Dourado; M.E. De Lima; A. Silva Cunha. 2020. "PNPP-19, A synthetic peptide designed from Phoneutria nigriventer spider toxin is effective for glaucoma treatment in rats." Toxicon 182, no. : S23.

Journal article
Published: 04 April 2019 in Toxins
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Bacterial keratitis is an ocular infection that can lead to severe visual disability. Staphylococcus aureus is a major pathogen of the eye. We recently demonstrated the strong antimicrobial activity of LyeTxI-b, a synthetic peptide derived from a Lycosa erithrognatha toxin. Herein, we evaluated a topical formulation (eye drops) containing LyeTxI-b to treat resistant bacterial keratitis. Keratitis was induced with intrastromal injection of 4 × 105 cells (4 µL) in New Zealand female white rabbits. Minimum inhibitory concentration (MIC) and biofilm viability were determined. LyeTxI-b ocular toxicity was evaluated through chorioallantoic membrane and Draize tests. One drop of the formulation (LyeTxI-b 28.9 µmol/L +0.5% CMC in 0.9% NaCl) was instilled into each eye four times a day, for a week. Slit-lamp biomicroscopy analysis, corneal histopathological studies and cellular infiltrate quantification through myeloperoxidase (MPO) and N-acetylglucosaminidase (NAG) detection were performed. LyeTxI-b was very effective in the treatment of keratitis, with no signs of ocular toxicity. Planktonic bacteria MIC was 3.6 µmol/L and LyeTxI-b treatment reduced biofilm viability in 90%. LyeTxI-b eliminated bacteria and reduced inflammatory cellular activity in the eyes. Healthy and treated animals showed similar NAG and MPO levels. LyeTxI-b is a potent new drug to treat resistant bacterial keratitis, showing effective antimicrobial and anti-inflammatory activity.

ACS Style

Carolina Nunes Da Silva; Flavia Rodrigues Da Silva; Lays Fernanda Nunes Dourado; Pablo Victor Mendes Dos Reis; Rummenigge Oliveira Silva; Bruna Lopes Da Costa; Paula Santos Nunes; Flávio Almeida Amaral; Vera Lúcia Dos Santos; Maria Elena De Lima; Armando Da Silva Cunha Júnior. A New Topical Eye Drop Containing LyeTxI-b, A Synthetic Peptide Designed from A Lycosa erithrognata Venom Toxin, Was Effective to Treat Resistant Bacterial Keratitis. Toxins 2019, 11, 203 .

AMA Style

Carolina Nunes Da Silva, Flavia Rodrigues Da Silva, Lays Fernanda Nunes Dourado, Pablo Victor Mendes Dos Reis, Rummenigge Oliveira Silva, Bruna Lopes Da Costa, Paula Santos Nunes, Flávio Almeida Amaral, Vera Lúcia Dos Santos, Maria Elena De Lima, Armando Da Silva Cunha Júnior. A New Topical Eye Drop Containing LyeTxI-b, A Synthetic Peptide Designed from A Lycosa erithrognata Venom Toxin, Was Effective to Treat Resistant Bacterial Keratitis. Toxins. 2019; 11 (4):203.

Chicago/Turabian Style

Carolina Nunes Da Silva; Flavia Rodrigues Da Silva; Lays Fernanda Nunes Dourado; Pablo Victor Mendes Dos Reis; Rummenigge Oliveira Silva; Bruna Lopes Da Costa; Paula Santos Nunes; Flávio Almeida Amaral; Vera Lúcia Dos Santos; Maria Elena De Lima; Armando Da Silva Cunha Júnior. 2019. "A New Topical Eye Drop Containing LyeTxI-b, A Synthetic Peptide Designed from A Lycosa erithrognata Venom Toxin, Was Effective to Treat Resistant Bacterial Keratitis." Toxins 11, no. 4: 203.

Journal article
Published: 01 March 2019 in The Journal of Sexual Medicine
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With the aim of overcoming the high toxicity of PnTx2-6 (or δ-CNTX-Pn2a), a toxin from the venom of the armed spider (Phoneutria nigriventer), the 19-aminoacid peptide, PnPP-19 (P nigriventer potentiator peptide), was synthesized based on molecular modeling studies of PnTx2-6. PnPP-19 improved the erectile function of normotensive rats and mice, without eliciting side effects, and no signs of toxicity were observed. In addition, PnPP-19 was able to potentiate the effect of sildenafil. To evaluate the efficacy of PnPP-19 in hypertensive and diabetic mouse/rat models in restoring erectile function, after topical administration; verify the biodistribution of PnPP-19 administration (topical and intravenous), permeation, and cyclic guanosine monophosphate (cGMP)/nitric oxide via implication. Corpus cavernosum relaxation was evaluated using cavernous strips from male spontaneous hypertensive rats (SHR) and from streptozotocin (STZ)-diabetic mice contracted with phenylephrine and submitted to electrical field stimulation before and after incubation with PnPP-19 (10-8 mol/L, 10 minutes) or vehicle. This procedure was also used to determine cGMP/nitric oxide levels, at 8 Hz and to check the effect of PnPP-19 with sildenafil citrate. Biodistribution assays were performed using iodine 123-radiolabeled PnPP-19. In vivo erectile function was evaluated using intracavernosal pressure/main arterial pressure ratio in STZ-diabetic rats after PnPP-19 topical administration. PnPP-19 may become a new drug able to fill the gap in the pharmacologic treatment of erectile dysfunction, especially for hypertensive and diabetic individuals RESULTS: PnPP-19 potentiated corpus cavernosum relaxation, in both control and SHR rats. SHR-cavernosal tissue treated with PnPP-19 (1-32 Hz) reached the same relaxation levels as control Wistar rats (16 and 32 Hz). PnPP-19 treatment improved cavernosal tissue relaxation in STZ-diabetic mice and rats. PnPP-19 enhanced cGMP levels in STZ-diabetic mice corpus cavernosum strips. After topical or intravenous administration in rats, 123I-PnPP-19 was mainly recruited to the penis. When topically administered (400 μg/rat), PnPP-19 restores erectile function in STZ-diabetic rats, also improving it in healthy rats by increasing the intracavernosal pressure/main arterial pressure ratio. PnPP-19 exhibited an additive effect when co-administered with sildenafil, showing a novel mode of action regardless of phosphodiesterase type 5 inhibition. PnPP-19 seems to be an indicated drug to be tested to treat ED in diabetic and hypertensive patients. PnPP-19, although active by topical application and showing safety to human beings (not shown), has low permeability, about 10% of the applied dose. Our results showed that PnPP-19 may emerge as a potent new drug that can be topically administered, becoming a promising alternative for erectile dysfunction treatment. Nunes da Silva C, Pedrosa Nunes K, De Marco Almeida F, et al. PnPP-19 Peptide Restores Erectile Function In Hypertensive And Diabetic Animals Through Intravenous And Topical Administration. J Sex Med 2019;16:365-374.

ACS Style

Carolina Nunes da Silva; Kênia Pedrosa Nunes; Flávia De Marco Almeida; Fábio Lucas Silva Costa; Perla Villani Borges; Paulo Lacativa; Adriano Monteiro C. Pimenta; Maria Elena de Lima. PnPP-19 Peptide Restores Erectile Function in Hypertensive and Diabetic Animals Through Intravenous and Topical Administration. The Journal of Sexual Medicine 2019, 16, 365 -374.

AMA Style

Carolina Nunes da Silva, Kênia Pedrosa Nunes, Flávia De Marco Almeida, Fábio Lucas Silva Costa, Perla Villani Borges, Paulo Lacativa, Adriano Monteiro C. Pimenta, Maria Elena de Lima. PnPP-19 Peptide Restores Erectile Function in Hypertensive and Diabetic Animals Through Intravenous and Topical Administration. The Journal of Sexual Medicine. 2019; 16 (3):365-374.

Chicago/Turabian Style

Carolina Nunes da Silva; Kênia Pedrosa Nunes; Flávia De Marco Almeida; Fábio Lucas Silva Costa; Perla Villani Borges; Paulo Lacativa; Adriano Monteiro C. Pimenta; Maria Elena de Lima. 2019. "PnPP-19 Peptide Restores Erectile Function in Hypertensive and Diabetic Animals Through Intravenous and Topical Administration." The Journal of Sexual Medicine 16, no. 3: 365-374.

Journal article
Published: 01 August 2018 in Toxicon
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PhTx2 is the most toxic fraction from the venom of the spider Phoneutria nigriventer, being responsible to sodium entry into cortical synaptosomes, increasing the release of neurotransmitters, such as l-glutamate (L-Glu) and; acetylcholine. In this study, we investigated the action of a toxin purified from; PhTx2 fraction, called PnTx2-6 or δ-CNTX-Pn2a, on L-Glu release from rat; brain cortex synaptosomes, as well as its ability to induce blood-brain barrier permeability. PnTx2-6 increased L-Glu release from rat cortical brain synaptosomes in a time- and dose-dependent manner (EC50 = ∼20 nM; Tm = 16min), as measured by a fluorimetric method. The increase of L-Glu by PnTx2-6 was inhibited by tetrodotoxin. and partially inhibited by EGTA. Calcium channel blockers ω-conotoxin MVIIC (P/Q-types) and ω-conotoxin GVIA (N-type), were able to reduce the PnTx2-6-induced release of L-Glu, while nifedipine (L-type) did not show any inhibition. These findings suggest that thew release of L-Glu by PnTx2-6 is due its primary action on sodium channels, well-known to be target of this toxin. PnTx2-6 is able to potentiate penile erection and this effect may be related with the release of l-glutamate from the CNS, besides a local effect on corpus carvenosum, as previously shown by our group. If L-Glu release and penile erection potentiation are indeed correlated, then this toxin should be able to cross the blood brain barrier (BBB). Results by immunoblotting assays indicated a change in the expression of proteins associated with the paracellular and transcellular transport at the blood-brain barrier, suggesting a BBB dysfunction mediated by PnTx2-6. Therefore, PnTx2-6 may induce the release l-glutamate in the central nervous system, when injected peripherally.

ACS Style

Carolina Nunes da Silva; Rosângela Silva Lomeo; Fernanda Silva Torres; Marcia Helena Borges; Marta Cordeiro Nascimento; Maria Helena Rodrigues Mesquita-Britto; Catarina Rapôso; Adriano Monteiro De Castro Pimenta; Maria Alice Da Cruz-Höfling; Dawidson Assis Gomes; Maria Elena De Lima. PnTx2-6 (or δ-CNTX-Pn2a), a toxin from Phoneutria nigriventer spider venom, releases l-glutamate from rat brain synaptosomes involving Na+ and Ca2+ channels and changes protein expression at the blood-brain barrier. Toxicon 2018, 150, 280 -288.

AMA Style

Carolina Nunes da Silva, Rosângela Silva Lomeo, Fernanda Silva Torres, Marcia Helena Borges, Marta Cordeiro Nascimento, Maria Helena Rodrigues Mesquita-Britto, Catarina Rapôso, Adriano Monteiro De Castro Pimenta, Maria Alice Da Cruz-Höfling, Dawidson Assis Gomes, Maria Elena De Lima. PnTx2-6 (or δ-CNTX-Pn2a), a toxin from Phoneutria nigriventer spider venom, releases l-glutamate from rat brain synaptosomes involving Na+ and Ca2+ channels and changes protein expression at the blood-brain barrier. Toxicon. 2018; 150 ():280-288.

Chicago/Turabian Style

Carolina Nunes da Silva; Rosângela Silva Lomeo; Fernanda Silva Torres; Marcia Helena Borges; Marta Cordeiro Nascimento; Maria Helena Rodrigues Mesquita-Britto; Catarina Rapôso; Adriano Monteiro De Castro Pimenta; Maria Alice Da Cruz-Höfling; Dawidson Assis Gomes; Maria Elena De Lima. 2018. "PnTx2-6 (or δ-CNTX-Pn2a), a toxin from Phoneutria nigriventer spider venom, releases l-glutamate from rat brain synaptosomes involving Na+ and Ca2+ channels and changes protein expression at the blood-brain barrier." Toxicon 150, no. : 280-288.

Journal article
Published: 12 July 2018 in Current Drug Delivery
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Flávia De Marco Almeida; Carolina Nunes Silva; Sávia Caldeira De Araújo Lopes; Daniel Moreira Santos; Fernanda Silva Torres; Felipe Lima Cardoso; Patrícia Massara Martinelli; Elizabeth Ribeiro Da Silva; Maria Elena De Lima; Lucas Antonio Ferreira Miranda; Mônica Cristina Oliveira. Physicochemical Characterization and Skin Permeation of Cationic Transfersomes Containing the Synthetic Peptide PnPP-19. Current Drug Delivery 2018, 15, 1064 -1071.

AMA Style

Flávia De Marco Almeida, Carolina Nunes Silva, Sávia Caldeira De Araújo Lopes, Daniel Moreira Santos, Fernanda Silva Torres, Felipe Lima Cardoso, Patrícia Massara Martinelli, Elizabeth Ribeiro Da Silva, Maria Elena De Lima, Lucas Antonio Ferreira Miranda, Mônica Cristina Oliveira. Physicochemical Characterization and Skin Permeation of Cationic Transfersomes Containing the Synthetic Peptide PnPP-19. Current Drug Delivery. 2018; 15 (7):1064-1071.

Chicago/Turabian Style

Flávia De Marco Almeida; Carolina Nunes Silva; Sávia Caldeira De Araújo Lopes; Daniel Moreira Santos; Fernanda Silva Torres; Felipe Lima Cardoso; Patrícia Massara Martinelli; Elizabeth Ribeiro Da Silva; Maria Elena De Lima; Lucas Antonio Ferreira Miranda; Mônica Cristina Oliveira. 2018. "Physicochemical Characterization and Skin Permeation of Cationic Transfersomes Containing the Synthetic Peptide PnPP-19." Current Drug Delivery 15, no. 7: 1064-1071.

Review
Published: 24 February 2016 in Spider Venoms
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ACS Style

Maria Elena De Lima; Suely Gomes Figueiredo; Alessandra Matavel; Kenia Pedrosa Nunes; Carolina Nunes Da Silva; Flávia De Marco Almeida; Marcelo Ribeiro Vasconcelos Diniz; Marta Nascimento Do Cordeiro; Maria Stankiewicz; Paulo Sérgio Lacerda Beirão. Phoneutria nigriventer Venom and Toxins: A Review. Spider Venoms 2016, 71 -99.

AMA Style

Maria Elena De Lima, Suely Gomes Figueiredo, Alessandra Matavel, Kenia Pedrosa Nunes, Carolina Nunes Da Silva, Flávia De Marco Almeida, Marcelo Ribeiro Vasconcelos Diniz, Marta Nascimento Do Cordeiro, Maria Stankiewicz, Paulo Sérgio Lacerda Beirão. Phoneutria nigriventer Venom and Toxins: A Review. Spider Venoms. 2016; ():71-99.

Chicago/Turabian Style

Maria Elena De Lima; Suely Gomes Figueiredo; Alessandra Matavel; Kenia Pedrosa Nunes; Carolina Nunes Da Silva; Flávia De Marco Almeida; Marcelo Ribeiro Vasconcelos Diniz; Marta Nascimento Do Cordeiro; Maria Stankiewicz; Paulo Sérgio Lacerda Beirão. 2016. "Phoneutria nigriventer Venom and Toxins: A Review." Spider Venoms , no. : 71-99.

Journal article
Published: 01 November 2015 in Journal of Urology
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We designed a peptide, PnPP-19, comprising the potential active core of the Phoneutria nigriventer native toxin PnTx2-6. We investigated its role on erectile function, and its toxicity and immunogenicity. Erectile function was evaluated by the intracavernous pressure-to-mean arterial pressure ratio during electrical field stimulation on rat pelvic ganglia. Cavernous strips were contracted with phenylephrine and relaxation was induced by electrical field stimulation with or without PnPP-19 (10(-8) M). Activity on sodium channels was evaluated by electrophysiological screening of transfected channels on Xenopus oocytes and dorsal root ganglion cells. Antibodies were detected by indirect enzyme-linked immunosorbent assay in mice previously treated with the peptide. Histopathological studies were performed with mouse organs treated with different doses of PnPP-19. PnPP-19 was able to potentiate erection at 4 and 8 Hz in vivo and ex vivo. It showed no toxicity and low immunogenicity in mice, and did not affect sodium channels or rat hearts. PnPP-19 increased cyclic guanosine monophosphate levels at 8 Hz. This effect was inhibited by L-NAME (10(-4) M). Erectile function was partially inhibited by 7-nitroindazole (10(-5) M), a selective inhibitor of neuronal nitric oxide synthase. PnPP-19 potentiates erection in vivo and ex vivo via the nitric oxide/cyclic guanosine monophosphate pathway. It does not affect sodium channels or rat hearts and shows no toxicity and low immunogenicity. These findings make it a promising candidate as a novel drug in the therapy of erectile dysfunction.

ACS Style

Carolina Nunes Silva; Kenia Pedrosa Nunes; Fernanda Silva Torres; Juliana Silva Cassoli; Daniel Moreira Santos; Flávia De Marco Almeida; Alessandra Matavel; Jader Santos Cruz; Arthur Santos-Miranda; Allancer Divino C. Nunes; Carlos Henrique Castro; Ricardo Andrés Machado De Ávila; Carlos Chávez-Olórtegui; Stephanie Stransky Láuar; Liza Felicori; Jarbas Magalhães Resende; Elizabeth Ribeiro Da Silva Camargos; Márcia Helena Borges; Marta Nascimento Cordeiro; Steve Peigneur; Jan Tytgat; Maria Elena De Lima. PnPP-19, a Synthetic and Nontoxic Peptide Designed from a Phoneutria nigriventer Toxin, Potentiates Erectile Function via NO/cGMP. Journal of Urology 2015, 194, 1481 -1490.

AMA Style

Carolina Nunes Silva, Kenia Pedrosa Nunes, Fernanda Silva Torres, Juliana Silva Cassoli, Daniel Moreira Santos, Flávia De Marco Almeida, Alessandra Matavel, Jader Santos Cruz, Arthur Santos-Miranda, Allancer Divino C. Nunes, Carlos Henrique Castro, Ricardo Andrés Machado De Ávila, Carlos Chávez-Olórtegui, Stephanie Stransky Láuar, Liza Felicori, Jarbas Magalhães Resende, Elizabeth Ribeiro Da Silva Camargos, Márcia Helena Borges, Marta Nascimento Cordeiro, Steve Peigneur, Jan Tytgat, Maria Elena De Lima. PnPP-19, a Synthetic and Nontoxic Peptide Designed from a Phoneutria nigriventer Toxin, Potentiates Erectile Function via NO/cGMP. Journal of Urology. 2015; 194 (5):1481-1490.

Chicago/Turabian Style

Carolina Nunes Silva; Kenia Pedrosa Nunes; Fernanda Silva Torres; Juliana Silva Cassoli; Daniel Moreira Santos; Flávia De Marco Almeida; Alessandra Matavel; Jader Santos Cruz; Arthur Santos-Miranda; Allancer Divino C. Nunes; Carlos Henrique Castro; Ricardo Andrés Machado De Ávila; Carlos Chávez-Olórtegui; Stephanie Stransky Láuar; Liza Felicori; Jarbas Magalhães Resende; Elizabeth Ribeiro Da Silva Camargos; Márcia Helena Borges; Marta Nascimento Cordeiro; Steve Peigneur; Jan Tytgat; Maria Elena De Lima. 2015. "PnPP-19, a Synthetic and Nontoxic Peptide Designed from a Phoneutria nigriventer Toxin, Potentiates Erectile Function via NO/cGMP." Journal of Urology 194, no. 5: 1481-1490.

Review
Published: 07 March 2015 in Spider Venoms
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The venom of Phoneutria nigriventer spider has been extensively studied. It is highly neurotoxic, with clinical manifestations occurring a few minutes after the bite, mainly in children. Among the intoxication signs that may lead to neurogenic shock are agitation, somnolence, sweating, nausea, profuse vomiting, lacrimation, excessive salivation, hypertension, tachycardia, tachypnea, tremors, muscle spasms, and priapism. Many toxins from this venom have been purified and characterized for their structure and/or function. The most studied Phoneutria nigriventer toxins are PnTx1, PnTx2-5, and PnTx2-6, which show complex effects on sodium channel kinetics. PnTx2-5 and PnTx2-6 are both described as responsible for priapism; PnTx4(6-1) and PnTx4(5-5) show insecticidal activities and act on insect sodium channels; PnTkPs are muscle-active peptides; and nigriventrine is a piperidine derivative that has neuroactive properties and causes convulsive spells. PnTx3-3 and PnTx3-4 toxins were demonstrated to be effective on preventing cell death after ischemia injury. On the other hand, PnTx3-6 was shown to be efficient in the treatment of persistent pathological pain. The present chapter compiles biochemical, physiological, and pharmacological studies of fractions and purified toxins from Phoneutria nigriventer venom, showing their great potential as new tools for pharmacological studies and drug development.

ACS Style

Maria Elena de Lima; Suely Gomes Figueiredo; Alessandra Matavel; Kenia Pedrosa Nunes; Carolina Nunes da Silva; Flávia De Marco Almeida; Marcelo Ribeiro Vasconcelos Diniz; Marta Nascimento Do Cordeiro; Maria Stankiewicz; Paulo Sérgio Lacerda Beirão. Phoneutria nigriventer Venom and Toxins: A Review. Spider Venoms 2015, 1 -24.

AMA Style

Maria Elena de Lima, Suely Gomes Figueiredo, Alessandra Matavel, Kenia Pedrosa Nunes, Carolina Nunes da Silva, Flávia De Marco Almeida, Marcelo Ribeiro Vasconcelos Diniz, Marta Nascimento Do Cordeiro, Maria Stankiewicz, Paulo Sérgio Lacerda Beirão. Phoneutria nigriventer Venom and Toxins: A Review. Spider Venoms. 2015; ():1-24.

Chicago/Turabian Style

Maria Elena de Lima; Suely Gomes Figueiredo; Alessandra Matavel; Kenia Pedrosa Nunes; Carolina Nunes da Silva; Flávia De Marco Almeida; Marcelo Ribeiro Vasconcelos Diniz; Marta Nascimento Do Cordeiro; Maria Stankiewicz; Paulo Sérgio Lacerda Beirão. 2015. "Phoneutria nigriventer Venom and Toxins: A Review." Spider Venoms , no. : 1-24.

Journal article
Published: 01 July 2014 in Toxicon
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Crotoxin (Crtx), the main toxin in the venom of Crotalus durissus terrificus snake, is a heterodimer with a basic subunit, CB, and an acidic subunit, CA. CB is a phospholipase A2 that depends on CA to specifically bind to the cell membrane. This toxin acts in the central nervous system (CNS) causing chronic seizure effects and other cytotoxic effects. Here, we report its action on glutamate release in rat cerebral cortex synaptosomes. Aiming at a better understanding of the mechanism of action of Crtx, calcium channel blockers were used and internalization studies were performed in cerebellar granule neurons. Our results show that Crtx induces calcium-dependent glutamate release via N and P/Q calcium channels. In addition, the CB subunit of Crtx is shown to be internalized. This internalization does not depend on the presence of CA subunit neither on the PLA2 activity of CB. A correlation between CB internalization and glutamate release remains to be established.

ACS Style

Rosangela Da Silva Lomeo; Ana Paula De Faria Gonçalves; Carolina Nunes da Silva; André Tunes de Paula; Danielle Oliveira Costa Santos; Consuelo Latorre Fortes-Dias; Dawidson Gomes; Maria Elena de Lima. Crotoxin from Crotalus durissus terrificus snake venom induces the release of glutamate from cerebrocortical synaptosomes via N and P/Q calcium channels. Toxicon 2014, 85, 5 -16.

AMA Style

Rosangela Da Silva Lomeo, Ana Paula De Faria Gonçalves, Carolina Nunes da Silva, André Tunes de Paula, Danielle Oliveira Costa Santos, Consuelo Latorre Fortes-Dias, Dawidson Gomes, Maria Elena de Lima. Crotoxin from Crotalus durissus terrificus snake venom induces the release of glutamate from cerebrocortical synaptosomes via N and P/Q calcium channels. Toxicon. 2014; 85 ():5-16.

Chicago/Turabian Style

Rosangela Da Silva Lomeo; Ana Paula De Faria Gonçalves; Carolina Nunes da Silva; André Tunes de Paula; Danielle Oliveira Costa Santos; Consuelo Latorre Fortes-Dias; Dawidson Gomes; Maria Elena de Lima. 2014. "Crotoxin from Crotalus durissus terrificus snake venom induces the release of glutamate from cerebrocortical synaptosomes via N and P/Q calcium channels." Toxicon 85, no. : 5-16.

Journal article
Published: 15 December 2010 in Toxicon
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In the current study, the putative cDNA for PnTx2-6 toxin of the Phoneutria nigriventer spider venom was cloned and expressed as tioredoxin fusion protein in the cytoplasm of Escherichia coli. The fusion protein was purified from the bacterial extracts by combination of immobilized Ni–ion affinity and gel filtration chromatographies. Then, it was cleaved by enterokinase and the generated recombinant PnTx2-6 (rPnTx2-6) was further purified by reverse-phase HPLC. Likewise the native toxin purified from the spider venom, rPnTx2-6 potentiates the erectile function when injected in rats. This result indicates that the production of functional recombinant PnTx2-6 might be an alternative to provide this basic and valuable tool for study, as well as for further understanding such complex physiological system, including its correlation with the central nervous system and local tissue factors.

ACS Style

F.S. Torres; C.N. Silva; L.F. Lanza; Agenor V. Santos; A.M.C. Pimenta; M.E. De Lima; M.R.V. Diniz. Functional expression of a recombinant toxin – rPnTx2-6 – active in erectile function in rat. Toxicon 2010, 56, 1172 -1180.

AMA Style

F.S. Torres, C.N. Silva, L.F. Lanza, Agenor V. Santos, A.M.C. Pimenta, M.E. De Lima, M.R.V. Diniz. Functional expression of a recombinant toxin – rPnTx2-6 – active in erectile function in rat. Toxicon. 2010; 56 (7):1172-1180.

Chicago/Turabian Style

F.S. Torres; C.N. Silva; L.F. Lanza; Agenor V. Santos; A.M.C. Pimenta; M.E. De Lima; M.R.V. Diniz. 2010. "Functional expression of a recombinant toxin – rPnTx2-6 – active in erectile function in rat." Toxicon 56, no. 7: 1172-1180.