Biochemical mechanism of corticoid-induced cleft palate in rats linked to anti-inflammatory action

Abstract

Glucocorticoids produce cleft palate in offspring of rodents in direct relation to their anti-inflammatory potency. Recently,the anti-inflammatory action of glucocorticoids has been shown to be inhibition of arachidonic acid release from membrane phospholipids in several different models of inflammation in direct relation to anti-inflammatory potency. Thus,we have determined whether the production of cleft palate in rat fetuses by dexamethasone 3.5 mg/kg on days 12 to 15 of gestation is affected by concurrent injections of arachidonic acid 300 mg/kg. This produced a marked correction of the degree of cleft palate produced by dexamethasone (59/146, 40.4% vs. 129/180, 71.7%; P=0. 034 Mann-Whitney test). Pregnant rats were also treated with either dexamethasone or saline on days 12 to 14 and 3H-arachidonic acid on day 15. After four hours fetuses of dexamethasone-treated animals had significantly increased uptake of 3H vs. controls. Moreover, the increased 3H was incorporated chiefly into phospholipid demonstrating a reverse of release of fetal palatal arachidonic acid.Thus, the teratogenic action of corticoids appears to be due to their anti-inflammatory action.