Acetazolamide with caffeine causes exencephaly in "resistant" SWV mice.
Pregnant SWV mice were treated on day 9 of gestation (PC) with 50 mg/kg of caffeine (CAFF), 200 mg/kg (LD) or 1000 mg/kg (HD) of acetazolamide (ACZM), or a combination of both agents, or on day 8 PC with both agents (ACZM + CAFF). Untreated (UNTD) and vehicle-treated (VEH) groups served as controls. The SWV strain is widely reported to be resistant to ACZM; it was resistant to ACZM or CAFF + ACZM when treated on day 9 of gestation, but a significant frequency of malformations, primarily exencephaly, was produced by ACZM + CAFF on day 8 PC. This study provides evidence that ACZM, coupled with a subteratogenic dose of caffeine can produce abnormalities in the "resistant" SWV mice, using the endpoint of exencephaly on day 8 of gestation. The mean number of ossified caudal vertebrae in day-9 treatments and ossified cervical vertebral centra in day-8 treatments were reduced. The frequency of ossification of the first cervical vertebra (C1) was reduced from 93% in UNTD to 39% in HD-ACZM day 9 PC and 69% in HD-ACZM + CAFF day 9 PC groups, and was also significantly reduced in the HD-ACZM + CAFF day-8 treated group.
Biology Department, DePaul University, Chicago, Illinois 60614.
S L
SL
Beck
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Urbano
D000086:Acetazolamide / Q000633:toxicity*; D000818:Animals; D001724:Birth Weight / Q000187:drug effects; D001921:Brain / Q000002:abnormalities*; D002110:Caffeine / Q000633:toxicity*; D002574:Cervical Vertebrae / Q000002:abnormalities; D004622:Embryo, Mammalian / Q000187:drug effects; D005260:Female; D005313:Fetal Death / Q000139:chemically induced; D008098:Litter Size / Q000187:drug effects; D051379:Mice; D008815:Mice, Inbred Strains; D010012:Osteogenesis / Q000187:drug effects; D011247:Pregnancy
D002110:Caffeine; D000086:Acetazolamide