Oxonic acid and fetal development: I. Embryotoxicity in mice

Feeding the uricase inhibitor potassium oxonate (K Ox) as 3( of the diet to pregnant mice during days 8-10 postconception caused a 95-98% incidence of embryonic mortality with resorption. The same treatment during days 10-13 of gestation caused no changes in litter size and fetal weight; however, if in addition to feeding K Ox, three concurrent i.v. injections of 2.5 mg/day of Na urate (Na UR) were given then 47% of the mouse fetuses were killed and resorbed. Intravenous Na urate alone during the same stages of early and middle pregnancy had no effect on fetal survival or development. A 3.6% incidence of cleft palate was caused in mice treated with the combination of K Ox and Na UR during middle pregnancy. In groups of mature nonpregnant female mice exposed to the same treatment regimens, serum uric acid, potassium and sodium were elevated in a treatment-related manner. Serum urea levels were unchanged. K Ox is lethal to mouse fetuses during early embryonic development. Hyperuricemia, hyperkalemia or hypernatremia are maternal alterations which may be responsible for, or contribute to this effect.