ArticleDigestive diseases and sciences1995
Chronic effects of misoprostol in combination with the NSAID, diclofenac, on gastrointestinal tract of pigs. Relation to diarrheagenic activity, leukocyte infiltration, and mucosal leukotrienes.
Article in Digestive diseases and sciences, 1995. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
2 citing papers in PubMed, 10 citations in OpenAlex.
- A Preliminary Study on the Relationship between Gastric Lesions and Anti-Inflammatory Drug Usage in Heavy Pigs.Veterinary sciences · 2023Article
- Effects of nitro-butoxyl- and butyl-esters of non-steroidal anti-inflammatory drugs compared with parent compounds on the contractility of digital arterial smooth muscle from the fallow deer (Dama dama).Inflammopharmacology · 2021Article
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Authors and funding
3 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
To determine the mode of protective effects of misoprostol against the chronic gastrointestinal ulceration from the NSAID, diclofenac, studies were undertaken in domestic pigs, a model of human gastrointestinal ulceration, to determine (1) the effects of repeated daily dosing for 10 days of diclofenac 5 mg/kg/day twice a day (as Voltaren tablets) on the gastrointestinal morphology, 59fe-red blood loss, mucosal myeloperoxidase (MPO) activity (as an indicator of leukocyte infiltration), and mucosal leukotrienes (LTS); and (2) the mucosal protective effects of 10-40 micrograms/kg/day misoprostol twice a day (as Cytotec tablets) given with diclofenac 5 mg/kg/day twice a day compared with diclofenac 5 mg/kg/day alone and aspirin 150 mg/kg/twice a day (USP tablets) as a standard. These effects were compared with the dose range for potential diarrheagenic effects of misoprostol (determined by fecal analysis of NA+, K+, CL-, CA2+, H2O, and phenol red transit) given alone or with diclofenac to determine if this could be discriminated from antiulcer effects of misoprostol. Plasma and gastric mucosal concentrations of the drugs were determined to establish if misoprostol affects diclofenac absorption/elimination, and vice versa. The results showed that: (1) diclofenac produced gastric mucosal damage without any prior or concurrent bleeding from the gastrointestinal tract, although aspirin significantly increased blood loss; (2) misoprostol produced a dose-related reduction in diclofenac-induced mucosal damage of the upper gastrointestinal tract; (3) no significant increase in mucosal MPO occurred with diclofenac despite mucosal damage being evident, (4) mucosal LTS were unaffected by the drug treatments; (5) plasma, gastric and intestinal concentrations of diclofenac were not affected by misoprostol, while conversely plasma misoprostol concentrations were not influenced by the diclofenac treatment; (6) no significant effects on fecal water, electrolyte, or phenol red transit times were observed with an of the drug-treatments; and (7) mild diarrhea observed as "loose bowel motions" was only observed in most pigs receiving the misoprostol treatments during fasting on days 9-10. Thus, misoprostol protects against chronic lesions/ulcers in the upper gastrointestinal tract from diclofenac without: (1) signs of diarrhea becoming evident (the latter occurring when there is reduced food intake), (2) generalized leukocyte infiltration or effects on mucosal LTs, or (3) any reduction in bioavailability of diclofenac.
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