title: Lectin from Abelmoschus esculentus reduces zymosan-induced temporomandibular joint inflammatory hypernociception in rats via heme oxygenase-1 pathway integrity and tnf-α and il-1β suppression.
abstract: Temporomandibular joint (TMJ) disorders show inflammatory components, heavily impacting on quality of life. Abelmoschus esculentus is largely cultivated in Northeastern Brazil for medicinal purposes, having it shown anti-inflammatory activity. We evaluated A. esculentus lectin (AEL) efficacy in reducing zymosan-induced temporomandibular joint inflammatory hypernociception in rats along with the mechanism of action through which it exerts anti-inflammatory activity. Animals were pre-treated with AEL (0.01, 0.1 or 1mg/kg) before zymosan (Zy) injection in the TMJ to determine anti-inflammatory activity. To analyse the possible effect of the hemeoxygenase-1 (HO-1) and the nitric oxide (NO) pathways on AEL efficacy, animals were pre-treated with ZnPP-IX (3mg/kg), a specific HO-1 inhibitor, or aminoguanidine (30mg/kg), a selective iNOS inhibitor, before AEL administration. Von Frey test evaluated inflammatory hypernociception, synovial fluid collection was performed to determine leukocyte counting and myeloperoxidase (MPO) activity 6h after Zy injection, and Evans Blue extravasation determined vascular permeability. TMJ tissue was collected for histopathological analysis (H&E) and immunohistochemistry (TNF-α, IL-1β, HO-1). In addition, TMJ tissue and trigeminal ganglion collection was performed for TNF-α and IL-1β dosage (ELISA). AEL increased inflammatory nociceptive threshold, reduced leukocyte influx along with MPO activity, leukocyte influx into the synovial membrane, and Evans Blue extravasation. It promoted HO-1 overexpression whilst decreased TNF-α and IL-1β expression in the TMJ tissue. AEL reduced TNF-α and IL-1β levels in TMJ tissue and trigeminal ganglion. AEL effects, however, were not observed in the presence of ZnPP-IX. These findings suggest that AEL efficacy depends on TNF-α/IL-1β inhibition and HO-1 pathway integrity.
authors.affiliation: Master in Biotechnology, Federal University of Ceará, Avenida Comandante Maurocélio Rocha Pontes, 100 Derby, CEP: 62.042-280 Sobral, Ceará, Brazil. Electronic address: raul.sf2@gmail.com.
authors.forename: Raul Sousa
authors.initials: RS
authors.lastname: Freitas
authors.affiliation: Northeast Biotechnology Network (Renorbio), Federal University of Pernambuco, Av. Prof. Moraes Rego, 1235 Cidade Universitária, CEP: 50670-901 Recife, Pernambuco, Brazil. Electronic address: danielleval@hotmail.com.
authors.forename: Danielle Rocha
authors.initials: DR
authors.lastname: do Val
authors.affiliation: Faculty of Dentistry, Federal University of Ceará, Avenida Comandante Maurocélio Rocha Pontes, 100 Derby, CEP: 62.042-280 Sobral, Ceará, Brazil. Electronic address: esterfrota@hotmail.com.
authors.forename: Maria Ester Frota
authors.initials: ME
authors.lastname: Fernandes
authors.affiliation: Faculty of Dentistry, Federal University of Ceará, Avenida Comandante Maurocélio Rocha Pontes, 100 Derby, CEP: 62.042-280 Sobral, Ceará, Brazil. Electronic address: ffer9352@uni.sydney.edu.au.
authors.forename: Francisco Isaac Fernandes
authors.initials: FI
authors.lastname: Gomes
authors.affiliation: Department of Molecular Biology, Federal University of Paraíba, Cidade Universitária, CEP: 58059-900 João Pessoa, Paraíba, Brazil. Electronic address: thales_lacerda2@hotmail.com.
authors.forename: José Thalles Jocelino Gomes
authors.initials: JT
authors.lastname: de Lacerda
authors.affiliation: Department of Molecular Biology, Federal University of Paraíba, Cidade Universitária, CEP: 58059-900 João Pessoa, Paraíba, Brazil. Electronic address: santi.tatiane@gmail.com.
authors.forename: Tatiane
authors.initials: T
authors.lastname: SantiGadelha
authors.affiliation: Department of Molecular Biology, Federal University of Paraíba, Cidade Universitária, CEP: 58059-900 João Pessoa, Paraíba, Brazil. Electronic address: calbgadelha@gmail.com.
authors.forename: Carlos Alberto
authors.initials: CA
authors.lastname: de Almeida Gadelha
authors.affiliation: Faculty of Medicine, Federal University of Ceará, Avenida Comandante Maurocélio Rocha Pontes, 100 Derby, CEP: 62.042-280 Sobral, Ceará, Brazil. Electronic address: pintovicente@gmail.com.
authors.forename: Vicente
authors.initials: V
authors.lastname: de Paulo Teixeira Pinto
authors.affiliation: Faculty of Medicine, Federal University of Ceará, Avenida Comandante Maurocélio Rocha Pontes, 100 Derby, CEP: 62.042-280 Sobral, Ceará, Brazil. Electronic address: gerardocristino@uol.com.br.
authors.forename: Gerardo
authors.initials: G
authors.lastname: Cristino-Filho
authors.affiliation: Faculty of Dentistry, Federal University of Ceará, Avenida Comandante Maurocélio Rocha Pontes, 100 Derby, CEP: 62.042-280 Sobral, Ceará, Brazil. Electronic address: karuzaalves@yahoo.com.br.
authors.forename: Karuza Maria Alves
authors.initials: KM
authors.lastname: Pereira
authors.affiliation: Department of Morphology, Federal University of Ceará, Rua Delmiro de Farias, Porangabussu, CEP:60440-261 Fortaleza, Ceará, Brazil. Electronic address: gerlybrito@hotmail.com.
authors.forename: Gerly Anne
authors.initials: GA
authors.lastname: de Castro Brito
authors.affiliation: Northeast Biotechnology Network (Renorbio), Federal University of Pernambuco, Av. Prof. Moraes Rego, 1235 Cidade Universitária, CEP: 50670-901 Recife, Pernambuco, Brazil. Electronic address: mirnabrayner@gmail.com.
authors.forename: Mirna Marques
authors.initials: MM
authors.lastname: Bezerra
authors.affiliation: Faculty of Dentistry, Federal University of Ceará, Avenida Comandante Maurocélio Rocha Pontes, 100 Derby, CEP: 62.042-280 Sobral, Ceará, Brazil. Electronic address: helliadachaves@yahoo.com.br.
authors.forename: Hellíada Vasconcelos
authors.initials: HV
authors.lastname: Chaves
mesh_terms: D028483:Abelmoschus / Q000276:immunology*; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use*; D002199:Capillary Permeability / Q000187:drug effects; D051547:Heme Oxygenase-1 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D007249:Inflammation / Q000139:chemically induced / Q000188:drug therapy*; D053583:Interleukin-1beta / Q000378:metabolism; D008297:Male; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D044343:Overnutrition / Q000139:chemically induced / Q000188:drug therapy*; D037121:Plant Lectins / Q000627:therapeutic use*; D011524:Protoporphyrins / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction / Q000187:drug effects; D013704:Temporomandibular Joint / Q000187:drug effects* / Q000473:pathology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D015054:Zymosan
chemical_list: D000893:Anti-Inflammatory Agents; D053583:Interleukin-1beta; D037121:Plant Lectins; D011524:Protoporphyrins; D014409:Tumor Necrosis Factor-alpha; C017803:zinc protoporphyrin; D015054:Zymosan; D052247:Nitric Oxide Synthase Type II; D051547:Heme Oxygenase-1
keywords: Abelmoschus esculentus; HO-1 pathway; Hypernociception; Temporomandibular joint