title: Complementarity of in vitro and in vivo models for the evaluation of gastro-protective effects of pharmacological substances.
abstract: Gastric mucosa is frequently exposed to various gastric irritants, and there is a continuing requirement to develop new gastro-protective agents. This study compares the effects of three such agents, sucralfate, rebamipide, and cimetidine in both in vivo and in vitro indomethacin-induced gastric damage models. For the in vivo approach, rats were orally administered sucralfate, rebamipide, and cimetidine at 300 mg/kg before an acute dose of indomethacin (30 mg/kg). Gastric lesions were then macroscopically examined. For the in vitro approach, gastric mucosal cells were incubated with sucralfate (3 and 5 mg/mL), rebamipide (0.3 and 1 mm), and cimetidine (10 and 50 μg/mL) before exposure to indomethacin (3.8 mm). The release of lactate dehydrogenase (LDH) and mitochondrial function were then measured. Sucralfate, rebamipide, and cimetidine displayed gastro-protective effects in vivo (decreased number of gastric ulcers: -50% P < 0.05, -22% NS, and -69% P < 0.05, respectively, and reduced length of gastric lesions: -62% P < 0.05, -29% NS, and -70% P < 0.001, respectively). Cell damage induced by indomethacin in vitro was inhibited by sucralfate (LDH release) and by rebamipide and cimetidine (mitochondrial function and LDH release). In contrast, sucralfate accentuated the indomethacin-induced decrease in mitochondrial function. Although cultured gastric cells offer a promising tool for evaluating the cytotoxic or protective effects of test compounds, data from in vivo models are still needed to confirm in vitro data. Using both approaches provides more comprehensive insight into the effects of test compounds on the gastric mucosa.
authors.affiliation: Porsolt S.A.S., Z.A. de Glatigné, 53940, Le Genest-Saint-Isle, France.
authors.forename: Sonia
authors.initials: S
authors.lastname: Goineau
authors.affiliation: Porsolt S.A.S., Z.A. de Glatigné, 53940, Le Genest-Saint-Isle, France.
authors.forename: Vincent
authors.initials: V
authors.lastname: Castagné
mesh_terms: D000409:Alanine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D000897:Anti-Ulcer Agents / Q000008:administration & dosage / Q000494:pharmacology; D002927:Cimetidine / Q000008:administration & dosage / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005753:Gastric Mucosa / Q000187:drug effects* / Q000473:pathology; D007213:Indomethacin / Q000633:toxicity; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008297:Male; D008928:Mitochondria / Q000473:pathology; D015363:Quinolones / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013276:Stomach Ulcer / Q000139:chemically induced / Q000517:prevention & control*; D013392:Sucralfate / Q000008:administration & dosage / Q000494:pharmacology*
chemical_list: D000897:Anti-Ulcer Agents; D015363:Quinolones; D013392:Sucralfate; D002927:Cimetidine; D007770:L-Lactate Dehydrogenase; C052785:rebamipide; D000409:Alanine; D007213:Indomethacin
keywords: gastric injury; indomethacin; primary cell culture; rat; ulcer