Role of hypergastrinemia in the antiatrophy effect of 2,3,7,8-tetrachlorodibenzo-p-dioxin on oxyntic gland mucosa of the rat stomach.
Atrophy of the gastrointestinal mucosa that occurs in pair-fed control rats is not observed in 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)-treated rats (1). Our objective was to determine if the gastrointestinal trophic hormone, gastrin, is involved in the antiatrophy effect of TCDD on the gut mucosa. Adult male Sprague-Dawley rats treated with 100 micrograms/kg of TCDD were slightly hypergastrinemic 7 days after dosing and markedly hypergastrinemic 14 days after treatment whereas pair-fed control rats were normogastrinemic. After 14 days of feed restriction, atrophy of the oxyntic gland and ileum mucosa occurred in pair-fed control rats but only atrophy of the ileum mucosa developed in TCDD-treated animals. The oxyntic gland mucosa of TCDD-treated rats was protected from mucosa atrophy as well as from mucosa erosions. The protection against feed restriction-induced atrophy was demonstrated by measurements of oxyntic gland mucosal height and DNA and protein content. Since hypergastrinemia stimulates growth of oxyntic gland mucosa, but not ileum mucosa, the antiatrophy effect of TCDD on mucosa of the oxyntic gland might in part be due to hypergastrinemia. In support of this interpretation, TCDD treatment exerted an antiatrophy effect on the oxyntic gland mucosa only when TCDD-treated animals were hypergastrinemic. For example, hypergastrinemia does not develop within the first 48 hr after TCDD administration, and TCDD treatment affords no protection against fasting-induced atrophy of the oxyntic gland mucosa during this time. On the other hand, the ability of TCDD treatment to protect against feed restriction-induced erosions of the oxyntic gland mucosa might be mediated by hypergastrinemia since these events occur at a later time.(ABSTRACT TRUNCATED AT 250 WORDS)
Theobald
H M
HM
School of Pharmacy, University of Wisconsin, Madison 53706.
Mably
T A
TA
Ingall
G B
GB
Peterson
R E
RE
D000818:Animals; D000897:Anti-Ulcer Agents; D001284:Atrophy / Q000517:prevention & control; D001835:Body Weight / Q000187:drug effects; D004435:Eating / Q000187:drug effects; D005215:Fasting / Q000097:blood; D005753:Gastric Mucosa / Q000187:drug effects* / Q000254:growth & development / Q000473:pathology; D005755:Gastrins / Q000097:blood*; D008297:Male; D010295:Parietal Cells, Gastric / Q000187:drug effects*; D000072317:Polychlorinated Dibenzodioxins / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains
D000897:Anti-Ulcer Agents; D005755:Gastrins; D000072317:Polychlorinated Dibenzodioxins