title: PhTx3-4, a Spider Toxin Calcium Channel Blocker, Reduces NMDA-Induced Injury of the Retina.
abstract: The in vivo neuroprotective effect of PhTx3-4, a spider toxin N-P/Q calcium channel blocker, was studied in a rat model of NMDA-induced injury of the retina. NMDA (N-Methyl-D-Aspartate)-induced retinal injury in rats reduced the b-wave amplitude by 62% ± 3.6%, indicating the severity of the insult. PhTx3-4 treatment increased the amplitude of the b-wave, which was almost equivalent to the control retinas that were not submitted to injury. The PhTx3-4 functional protection of the retinas recorded on the ERG also was observed in the neuroprotection of retinal cells. NMDA-induced injury reduced live cells in the retina layers and the highest reduction, 84%, was in the ganglion cell layer. Notably, PhTx3-4 treatment caused a remarkable reduction of dead cells in the retina layers, and the highest neuroprotective effect was in the ganglion cells layer. NMDA-induced cytotoxicity of the retina increased the release of glutamate, reactive oxygen species (ROS) production and oxidative stress. PhTx3-4 treatment reduced glutamate release, ROS production and oxidative stress measured by malondialdehyde. Thus, we presented for the first time evidence of in vivo neuroprotection from NMDA-induced retinal injury by PhTx3-4 (-ctenitoxin-Pn3a), a spider toxin that blocks N-P/Q calcium channels.
authors.affiliation: Institute of Education and Research Santa Casa Belo Horizonte-Laboratory of Toxins, Rua Domingos Vieira 590, Belo Horizonte, Minas Gerais 30150-240, Brazil. nancysbinda@yahoo.com.br.
authors.forename: Nancy Scardua
authors.initials: NS
authors.lastname: Binda
authors.affiliation: Institute of Education and Research Santa Casa Belo Horizonte-Laboratory of Toxins, Rua Domingos Vieira 590, Belo Horizonte, Minas Gerais 30150-240, Brazil. charlespetruceli@hotmail.com.
authors.forename: Charles Porto Petruceli
authors.initials: CP
authors.lastname: Carayon
authors.affiliation: Institute of Education and Research Santa Casa Belo Horizonte-Laboratory of Toxins, Rua Domingos Vieira 590, Belo Horizonte, Minas Gerais 30150-240, Brazil. rafaelagostini@uol.com.br.
authors.forename: Rafael Mourão
authors.initials: RM
authors.lastname: Agostini
authors.affiliation: Institute of Education and Research Santa Casa Belo Horizonte-Laboratory of Toxins, Rua Domingos Vieira 590, Belo Horizonte, Minas Gerais 30150-240, Brazil. anapinheirofar@gmail.com.
authors.forename: Ana Cristina do Nascimento
authors.initials: AC
authors.lastname: Pinheiro
authors.affiliation: Ezequiel Dias Foundation (FUNED), Laboratory of Biochemistry, Rua Conde Pereira Carneiro 80, Belo Horizonte, Minas Gerais 30510-010, Brazil. martadonascimento.phoneutria@gmail.com.
authors.forename: Marta Nascimento
authors.initials: MN
authors.lastname: Cordeiro
authors.affiliation: Faculty of Medicine, Minas Gerais Federal University, Neuroscience Laboratory, Av. Alfredo Balena 190, Belo Horizonte, Minas Gerais 30130-100, Brazil. romanosilva@gmail.com.
authors.forename: Marco Aurélio Romano
authors.initials: MA
authors.lastname: Silva
authors.affiliation: Institute of Education and Research Santa Casa Belo Horizonte-Laboratory of Toxins, Rua Domingos Vieira 590, Belo Horizonte, Minas Gerais 30150-240, Brazil. jufigueira2003@yahoo.com.br.
authors.forename: Juliana Figueira
authors.initials: JF
authors.lastname: Silva
authors.affiliation: Institute of Education and Research Santa Casa Belo Horizonte-Laboratory of Toxins, Rua Domingos Vieira 590, Belo Horizonte, Minas Gerais 30150-240, Brazil. elizetemrpereira@yahoo.com.br.
authors.forename: Elizete Maria Rita
authors.initials: EM
authors.lastname: Pereira
authors.affiliation: Institute of Education and Research Santa Casa Belo Horizonte-Laboratory of Toxins, Rua Domingos Vieira 590, Belo Horizonte, Minas Gerais 30150-240, Brazil. claudiojunior.biologia@gmail.com.
authors.forename: Claudio Antonio
authors.initials: CA
authors.lastname: da Silva Junior
authors.affiliation: Institute of Education and Research Santa Casa Belo Horizonte-Laboratory of Toxins, Rua Domingos Vieira 590, Belo Horizonte, Minas Gerais 30150-240, Brazil. celiojcjunior@gmail.com.
authors.forename: Célio José
authors.initials: CJ
authors.lastname: de Castro Junior
authors.affiliation: Department of Dentistry, Montes Claros State University, University Hospital, Health Laboratory Research, Montes Claros, Montes Claros, Minas Gerais 39401-001, Brazil. andreluizguimaraes@gmail.com.
authors.forename: Andre Luiz Sena
authors.initials: AL
authors.lastname: Guimarães
authors.affiliation: Institute of Education and Research Santa Casa Belo Horizonte-Laboratory of Toxins, Rua Domingos Vieira 590, Belo Horizonte, Minas Gerais 30150-240, Brazil. marcusvgomez@gmail.com.
authors.forename: Marcus Vinicius
authors.initials: MV
authors.lastname: Gomez
mesh_terms: D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology / Q000627:therapeutic use*; D004596:Electroretinography; D018698:Glutamic Acid / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D016202:N-Methylaspartate; D009479:Neuropeptides / Q000494:pharmacology / Q000627:therapeutic use*; D018696:Neuroprotective Agents / Q000494:pharmacology / Q000627:therapeutic use*; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism; D012164:Retinal Diseases / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D013111:Spider Venoms / Q000494:pharmacology / Q000627:therapeutic use*; D014822:Vitreous Body / Q000378:metabolism
chemical_list: D002121:Calcium Channel Blockers; D009479:Neuropeptides; D018696:Neuroprotective Agents; D017382:Reactive Oxygen Species; D013111:Spider Venoms; C098736:Tx3 neurotoxin; D018698:Glutamic Acid; D016202:N-Methylaspartate
keywords: Neuroprotection; PhTx3-4; phoneutria nigriventer; retina; spider toxins