Gastric mucosal adaptation to diclofenac injury.
Adaptation occurs to the gastric injury produced by nonsteroidal antiinflammatory drugs during continued dosing. The aim of this study was to identify characteristics of this phenomenon that might help in the search for underlying mechanisms. The time frame for onset and offset of adaptation of diclofenac (damage assessed planimetrically) was examined in rats. Adaptation to oral diclofenac took three to five days to develop, and persisted for up to five days after the last dose. It was also demonstrable after subcutaneous dosing or when injury was measured by a change in mucosal potential difference. Diclofenac-adapted rats were protected against injury induced by subsequent exposure to ethanol, indomethacin, aspirin, or piroxicam, indicating that adaptation is not specific to injury by the adapting agent. This cross-adaptation was dose-dependent and characterized histologically by a reduction in deep damage. In conclusion, gastric adaptation to diclofenac is mediated by mechanisms that take several days to develop and be lost. The route of administration appears to be unimportant, but the development of both adaptation and cross-adaptation is influenced by dosage size.
Skeljo
M V
MV
University of Melbourne Department of Medicine, Western Hospital, Australia.
Cook
G A
GA
Elliott
S L
SL
Giraud
A S
AS
Yeomans
N D
ND
D000222:Adaptation, Physiological; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000633:toxicity*; D001241:Aspirin / Q000633:toxicity; D004008:Diclofenac / Q000008:administration & dosage / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D004361:Drug Tolerance; D000431:Ethanol / Q000633:toxicity; D005753:Gastric Mucosa / Q000187:drug effects* / Q000473:pathology / Q000503:physiopathology; D007213:Indomethacin / Q000633:toxicity; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D010894:Piroxicam / Q000633:toxicity; D051381:Rats; D011919:Rats, Inbred Strains; D013997:Time Factors
D000894:Anti-Inflammatory Agents, Non-Steroidal; D010894:Piroxicam; D004008:Diclofenac; D000431:Ethanol; D001241:Aspirin; D007213:Indomethacin