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Activation of transient receptor potential vanilloid channel 4 contributes to the development of ethanol-induced gastric injury in mice.
Pacheco, Gabriella; Oliveira, Ana P; Noleto, Isabela R S G; Araújo, Andreza K; Lopes, André L F; Sousa, Francisca B M; Chaves, Letícia S; Alves, Even H P; Vasconcelos, Daniel F P; Araujo, Alyne R; Nicolau, LucasA D; Magierowski, Marcin; Medeiros, Jand Venes R.
Afiliação
  • Pacheco G; Biotechnology and Biodiversity Center Research (BIOTEC), Post-graduation Program in Biotechnology, Federal University of the Parnaíba Delta (UFDPar), Parnaíba, PI, Brazil.
  • Oliveira AP; The Northeastern Biotechnology Network (RENORBIO), Federal University of Piauí (UFPI), Teresina, PI, Brazil.
  • Noleto IRSG; The Northeastern Biotechnology Network (RENORBIO), Federal University of Piauí (UFPI), Teresina, PI, Brazil.
  • Araújo AK; Biotechnology and Biodiversity Center Research (BIOTEC), Post-graduation Program in Biotechnology, Federal University of the Parnaíba Delta (UFDPar), Parnaíba, PI, Brazil.
  • Lopes ALF; Biotechnology and Biodiversity Center Research (BIOTEC), Post-graduation Program in Biotechnology, Federal University of the Parnaíba Delta (UFDPar), Parnaíba, PI, Brazil.
  • Sousa FBM; The Northeastern Biotechnology Network (RENORBIO), Federal University of Piauí (UFPI), Teresina, PI, Brazil.
  • Chaves LS; Biotechnology and Biodiversity Center Research (BIOTEC), Post-graduation Program in Biotechnology, Federal University of the Parnaíba Delta (UFDPar), Parnaíba, PI, Brazil.
  • Alves EHP; Biotechnology and Biodiversity Center Research (BIOTEC), Post-graduation Program in Biotechnology, Federal University of the Parnaíba Delta (UFDPar), Parnaíba, PI, Brazil.
  • Vasconcelos DFP; Biotechnology and Biodiversity Center Research (BIOTEC), Post-graduation Program in Biotechnology, Federal University of the Parnaíba Delta (UFDPar), Parnaíba, PI, Brazil; The Northeastern Biotechnology Network (RENORBIO), Federal University of Piauí (UFPI), Teresina, PI, Brazil.
  • Araujo AR; Biotechnology and Biodiversity Center Research (BIOTEC), Post-graduation Program in Biotechnology, Federal University of the Parnaíba Delta (UFDPar), Parnaíba, PI, Brazil.
  • Nicolau LD; Biotechnology and Biodiversity Center Research (BIOTEC), Post-graduation Program in Biotechnology, Federal University of the Parnaíba Delta (UFDPar), Parnaíba, PI, Brazil.
  • Magierowski M; Gaseous Mediators and Experimental Gastroenterology Laboratory, Department of Physiology, Jagiellonian University Medical College, Cracow, Poland.
  • Medeiros JVR; Biotechnology and Biodiversity Center Research (BIOTEC), Post-graduation Program in Biotechnology, Federal University of the Parnaíba Delta (UFDPar), Parnaíba, PI, Brazil; The Northeastern Biotechnology Network (RENORBIO), Federal University of Piauí (UFPI), Teresina, PI, Brazil. Electronic address:
Eur J Pharmacol ; 902: 174113, 2021 Jul 05.
Article em En | MEDLINE | ID: mdl-33901460
ABSTRACT
The transient receptor potential vanilloid channel 4 (TRPV4) is associated with the development of several pathologies, particularly gastric disorders. However, there are no studies associating this receptor with the pathophysiology of gastric erosions. The aim of this study was to investigate the role of TRPV4 in the development of ethanol-induced gastric damage in vivo. Gastric lesions were induced by ethanol in Swiss mice pretreated with TRPV4 antagonists, GSK2193874 (0.1; 0.3 and 0.9 mg/kg) or Ruthenium red (0.03; 0.1 or 0.3 mg/kg) or its agonist, GSK1016790A (0.9 mg/kg). Gastric mucosal samples were taken for histopathology, immunohistochemistry, atomic force microscopy and evaluation of antioxidant parameters. The gastric mucus content and TRPV4 mRNA expression were analyzed. Ethanol exposure induced upregulation of gastric mRNA and protein expression of TRPV4. TRPV4 blockade promoted gastroprotection against ethanol-induced injury on macro- and microscopic levels, leading to reduced hemorrhage, cell loss and edema and enhanced gastric mucosal integrity. Moreover, an increase in superoxide dismutase (SOD) and glutathione (GSH) activity was observed, followed by a decrease in malondialdehyde (MDA) levels. TRPV4 blockade during alcohol challenge reestablished gastric mucus content. The combination of TRPV4 agonist and ethanol revealed macroscopic exacerbation of gastric damage area. Our results confirmed the association of TRPV4 with the development of gastric injury, showing the importance of this receptor for further investigations in the field of gastrointestinal pathophysiology and pharmacology.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Úlcera Gástrica / Canais de Cátion TRPV Limite: Animals Idioma: En Revista: Eur J Pharmacol Ano de publicação: 2021 Tipo de documento: Article País de afiliação: Brasil

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Úlcera Gástrica / Canais de Cátion TRPV Limite: Animals Idioma: En Revista: Eur J Pharmacol Ano de publicação: 2021 Tipo de documento: Article País de afiliação: Brasil