Butylated hydroxyanisole (BHA) does not cause forestomach hyperplasia by inhibiting the release of gastric mucus.
High doses of BHA cause hyperplasia and subsequent neoplasia in the rodent forestomach and can inhibit gastric prostaglandin (PG) synthesis in vitro. This paper examines the hypothesis that BHA induced forestomach hyperplasia occurs in response to a reduction of gastric mucus, with consequent irritation of the forestomach. This could result from inhibition of the formation of the PG's which mediate the synthesis and release of protective mucus. Groups of 10 rats received 0 or 2% BHA in the diet for 1 or 3 weeks and a positive control group was fed a diet containing indomethacin (3.5 mg/kg), a potent inhibitor of PG synthesis. After 1 week BHA caused focal erosion and ulceration of the forestomach consistent with an irritant effect, but 2 weeks later the epithelium was healed, thickened and markedly hyperplastic. Histochemical staining for mucus showed that the development of forestomach hyperplasia was associated with increased amounts of gastric and duodenal mucus and increased numbers of serotonergic-cells in the gastric and duodenal epithelium. In contrast, indomethacin caused a marked reduction in both gastric and Brunner's gland mucus. Neither BHA nor indomethacin exerted an effect on one specific type of mucus (viz: neutral, acidic or mixed) in the stomach. These results do not support the hypothesis that forestomach hyperplasia arises from an inhibition of either the synthesis or release of gastric mucus. It is possible that the increased numbers of serotonergic-cells are related to the initial ulcerative, or subsequent hyperplastic response.
Lauriault
V
V
Robens Institute, Surrey University, Guildford, U.K.
Grasso
P
P
Powell
C J
CJ
D000284:Administration, Oral; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D002011:Brunner Glands / Q000187:drug effects / Q000473:pathology; D002083:Butylated Hydroxyanisole / Q000633:toxicity*; D016861:Cyclooxygenase Inhibitors; D005753:Gastric Mucosa / Q000187:drug effects*; D006965:Hyperplasia / Q000139:chemically induced; D007213:Indomethacin / Q000494:pharmacology*; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D013270:Stomach / Q000187:drug effects* / Q000473:pathology
D016861:Cyclooxygenase Inhibitors; D002083:Butylated Hydroxyanisole; D007213:Indomethacin