Teratogenicity of edoferon kappa A, a molecule derived from salicylate, incultured rat embryos: Differences from salicylate and interaction with free oxygen radical scavenging enzymes

The effect of edoferon kappa A (E-KA), a non-specific immunomodulatory and anti-neoplastic chemical substance derived from the methyl form of salicyla te (acetyl salicylic acid; ASA), on mammalian embryos was studied and compa red to the effects of ASA. Rat embryos were cultured in vitro from 9.5 days of gestation for 48 h. E-KA (0.1-12.8 mg/ml) and ASA (0.1-0.6 mg/ml) were added to the whole rat serum. To investigate the interaction of these molec ules with antioxidant agents, the lowest effective concentrations of E-KA ( 0.6 mg/ml) and ASA (0.3 mg/ml) for all parameters were added to the culture media in the presence of superoxide dismutase (SOD) (30 U/ ml) or glutathi one (0.5 mu mol/ml). The growth and development of embryos was compared and each embryo was evaluated for the presence of any malformations. E-KA and ASA decreased growth and development in a concentration-responsive manner. There was also a concentration-related increase in overall dysmorphology (h aematoma in the yolk sac and neural system, open neural tube, abnormal tail torsion and the absence of fore limb bud). There were no statistically sig nificant differences between the control and embryos grown in the presence of 0.1-0.4 mg/ml E-KA, although the effects of ASA started at a concentrati on of 0.2 mg/ml. Embryos showed significant growth retardation in all scori ng criteria and severe malformations when 0.5-3.2 mg/ml E-KA and 0.3-0.6 mg /ml ASA were added. When SOD was added, there was a significant decrease in the incidence of malformations and growth and developmental parameters wer e increased but this decrease never reached the control level. We concluded that E-KA has direct toxic effects on the developing embryo but at much hi gher concentrations than ASA, and the teratogenic effects of these molecule s might be related to free oxygen radicals.