Teratogenic effects of combined use of anti-kidney serum and E-64 in the rat.

The teratogenic effects of rabbit anti-rat-kidney serum (AKS) combined with E-64 (a thiol protease inhibitor) were examined. Wistar rats were injected with 10 or 20 mg/kg of E-64 on days 9 and 10 of gestation, and with a subteratogenic dose (1 ml/kg) of AKS on day 9 or day 10. The most common malformations were hydronephrosis, hydrocephalus, ureteral dilatation, microphthalmia, anophthalmia, and heart defects. When AKS was given on day 9 or 10, the incidence of malformations was about 7% (10 mg/kg group) and 24% (20 mg/kg group). This indicated that the types of malformations are similar to those produced by AKS and E-64, and there is a synergistic effect between AKS and E-64.