BACKGROUND: The mechanisms responsible for the gastric ulcerogenic effect of indomethacin are unclear. The importance of basal acid secretion on morphological changes by indomethacin was investigated. METHODS: Gastric lesions were macroscopically evaluated 6 h after indomethacin, 20 mg/kg intragastrically, in rats pre-treated with omeprazole (10-100 mumol/kg intragastrically) or lansoprazole (3-30 mumol/kg intragastrically). Glandular mucosa was processed for light, scanning and transmission electron microscopy 3 and 6 h after indomethacin in rats pre-treated with omeprazole (100 mumol/kg) or lansoprazole (30 mumol/kg). RESULTS: After 3 h, indomethacin caused extensive vasocongestion, oedema in the subepithelial region and superficial erosions. After 6 h, deeply extending focal necrosis involved 11% of the tissue. Leukocyte margination was occasionally seen at 3 h and consistently present at 6 h. Only at 6 h were endothelial cells altered. In rats pre-treated with omeprazole (100 mumol/kg) or lansoprazole (30 mumol/kg) grossly visible lesions were prevented. Oedema, erosions and necrosis were absent. Vasocongestion, vascular leakage and leukocytic margination were seen both at 3 and 6 h while no major damage of endothelial cells was observed. CONCLUSION: Indomethacin appears primarily to alter microcirculation, and microcirculation damage is dependent on acid for the progression to haemorrhagic lesions.
BACKGROUND: The mechanisms responsible for the gastric ulcerogenic effect of indomethacin are unclear. The importance of basal acid secretion on morphological changes by indomethacin was investigated. METHODS: Gastric lesions were macroscopically evaluated 6 h after indomethacin, 20 mg/kg intragastrically, in rats pre-treated with omeprazole (10-100 mumol/kg intragastrically) or lansoprazole (3-30 mumol/kg intragastrically). Glandular mucosa was processed for light, scanning and transmission electron microscopy 3 and 6 h after indomethacin in rats pre-treated with omeprazole (100 mumol/kg) or lansoprazole (30 mumol/kg). RESULTS: After 3 h, indomethacin caused extensive vasocongestion, oedema in the subepithelial region and superficial erosions. After 6 h, deeply extending focal necrosis involved 11% of the tissue. Leukocyte margination was occasionally seen at 3 h and consistently present at 6 h. Only at 6 h were endothelial cells altered. In rats pre-treated with omeprazole (100 mumol/kg) or lansoprazole (30 mumol/kg) grossly visible lesions were prevented. Oedema, erosions and necrosis were absent. Vasocongestion, vascular leakage and leukocytic margination were seen both at 3 and 6 h while no major damage of endothelial cells was observed. CONCLUSION:Indomethacin appears primarily to alter microcirculation, and microcirculation damage is dependent on acid for the progression to haemorrhagic lesions.
Authors: V Savarino; G S Mela; P Zentilin; M A Cimmino; M Parisi; M R Mele; M Pivari; G Bisso; G Celle Journal: Dig Dis Sci Date: 1998-03 Impact factor: 3.199
Authors: Márcia Fernanda Correia Jardim Paz; Marcus Vinícius Oliveira Barros de Alencar; Rodrigo Maciel Paulino de Lima; André Luiz Pinho Sobral; Glauto Tuquarre Melo do Nascimento; Cristiane Amaral Dos Reis; Maria do Perpetuo Socorro de Sousa Coêlho; Maria Luísa Lima Barreto do Nascimento; Antonio Luiz Gomes Júnior; Kátia da Conceição Machado; Ag-Anne Pereira Melo de Menezes; Rosália Maria Torres de Lima; José Williams Gomes de Oliveira Filho; Ana Carolina Soares Dias; Antonielly Campinho Dos Reis; Ana Maria Oliveira Ferreira da Mata; Sônia Alves Machado; Carlos Dimas de Carvalho Sousa; Felipe Cavalcanti Carneiro da Silva; Muhammad Torequl Islam; João Marcelo de Castro E Sousa; Ana Amélia de Carvalho Melo Cavalcante Journal: Oxid Med Cell Longev Date: 2020-03-28 Impact factor: 6.543