Exposure-disease continuum for @entity21653 , a prototype ocular teratogen. 3. Intervention with XXXX .

@entity17594 @entity19943 @entity2125 @entity353 @entity19 @entity899 @entity4353 @entity5 @entity16490 @entity2659 @entity21653 @entity735 @entity1245 @entity600 @entity19479 @entity10402 @entity14417
BACKGROUND: Treatment of pregnant @entity19 with @entity21653 ( @entity17594 ) on Day 8 of gestation induces @entity4353 through a mechanism linked to the @entity899 @entity5 suppressor pathway. The present study defines the response of Day 8 @entity19 embryos through time with respect to pharmacologic intervention with @entity19943 , a ligand of the mitochondrial peripheral @entity1245 receptor ( @entity19479 ). METHODS: Pregnant @entity2659 @entity19 dosed with @entity17594 with or without @entity19943 on gestation Day 8 provided fetuses for teratologic evaluation on Day 14 and Day 17; HPLC measured @entity10402 ( @entity2125 / @entity2125 +) at 1.5 hr, RT-PCR measured mitochondrial 16S rRNA abundance at 3.0 hr, and @entity899 protein induction was assessed with immunostaining at 4.5 hr postexposure. RESULTS: The mean incidences of malformed fetuses were significantly higher in the 7.5 mg/kg @entity17594 treatment group (50.2% malformed) vs. the @entity17594 + 4.0 mg/kg @entity19943 co-treatment group (4.4% malformed). Malformed fetuses displayed a range of @entity735 that included @entity4353 and @entity16490 ( @entity14417 ). No @entity600 were observed in the control or @entity19943 alone groups. @entity19943 also protected litters from increased resorption rates and fetal @entity353 . It did not rescue early effects on @entity2125 balance (1.5 hr) or 16S rRNA expression (3.0 hr); however, the @entity899 response (4.5 hr) was downgraded in @entity17594 + @entity19943 embryos vs. @entity17594 alone. By delaying the administration of @entity19943 in 1.5 hr intervals it was determined that the window for protection closed between 4.5 to 6.0 hr after @entity17594 . CONCLUSIONS: The capacity of @entity19943 to suppress the pathogenesis of @entity4353 implies a critical role for mitochondrial peripheral @entity1245 receptors in the @entity899 -dependent mode of action of @entity17594 on ocular development.
