Salicylate Intoxication and Congenital Anomalies

Publisher Website
Google Scholar
Abstract
The nature of the production of congenital malformations in rats by maternal salicylate poisoning has been investigated by studying possible teratogenic roles of several of the known metabolic effects of salicylate intoxication. A teratogenic role of the direct peripheral cytotoxic effect of salicylate poisoning, uncoupling of oxidative phospho-rylation, appears unlikely in that 2,4-dinitrophenolate, an agent with a specific uncoupling action nearly identical to that of salicylate, does not produce anomalies. Neither maternal adrenalectomy nor exogenous cortisone administration modifies the rate of anomalies produced by salicylate. Consequently, it is concluded that the indirect toxic stimulation of the maternal hypothalamus leading to the release of adreno-cortical hormones is not involved in the teratogenicity of salicylate. The interaction of exogenous cortisone, DNP, and an acidic salt load also does not produce anomalies. A partial teratogenic role of the indirect effect of salicylate poisoning on electrolyte balance has been indicated by the marked increase in the anomaly rate of salicylate with an ammonium chloride load to the mother, and by the prevention of anomaly production by salicylate in mothers given a saline or a sodium bicarbonate load. The pronounced synergistic effect of ammonium chloride on salicylate teratogenicity appears to be due either to its raising the blood level of salicylate through acidification of the urine or to its action as a maternal stressing agent, or to both. These experiments, as a whole, do not indicate a precise dysembryogenic pathway. However, it appears that maternal stress is an important synergistic pathway in teratogenesis.