PMID- 8032692
OWN - NLM
STAT- MEDLINE
DCOM- 19940815
LR  - 20191101
IS  - 1056-9014 (Print)
IS  - 1056-9014 (Linking)
VI  - 2
IP  - 1
DP  - 1994
TI  - Interaction of dimethylsulfoxide and arachidonic acid with the teratogenic 
      effects of caffeine in mice.
PG  - 29-35
AB  - Dose-response of the teratogenic effect of caffeine (CA) and the potential role 
      of facial hematomas in the pathogenesis of caffeine-induced cleft palate were 
      investigated using CD1 mice treated with 150, 200, or 250 mg CA/kg i.p. on 
      gestational day (GD) 12. Dimethylsulfoxide (DMSO; 20%) and arachidonic acid (AA, 
      200 mg/kg) were administered along with CA (200 mg/kg) to study their interaction 
      with CA-induced teratogenesis and elevation in maternal glucocorticoids (MGC, 
      measured by RIA) on GD 13 and 14. Dose-dependent increase in the incidence of 
      cleft palate (CP) was noted in CA-exposed mice. High maternal deaths, an 
      increased number of resorptions, gross facial hematomas (GFH), and club foot (CF) 
      were produced only by the highest (250 mg/kg) dose of CA. Palates from all 
      offspring with GFH were clefted at this dose level. None of the control or 
      CA-treated nonclefted offspring had GFH or microscopic hematomas (MH). At 200 
      mg/kg of CA, DMSO in combination with CA actually increased CA-induced CP from 
      30% to 100% and also produced 100% GFH as compared to 0% by CA alone at this 
      dose. Greater than 50% of clefted offspring without GFH, given either dose (200 
      or 250 mg/kg) of CA, had MH. Very high levels of MGC were present in CA-treated 
      mice on GD 13 and 14. Although simultaneous administration of DMSO reduced the 
      magnitude of CA-induced MGC elevations on GD 14, the MGC levels remained high for 
      greater than 24 hours following CA exposure. Increase in maternal mortality and 
      fetal resorptions, a decrease in the number of live pups and their body weights, 
      and no change in the incidence of CP were seen when CA-treated mice were 
      simultaneously exposed to AA. These results suggest a correlation between 
      caffeine-induced FH and CP; a role for increased hematomagenic effects of DMSO in 
      its potentiation of the cleft-palatogenic effect of caffeine; and absence of a 
      role for AA-mediated effects of MGC in the causation of CA-induced CP and other 
      malformations.
FAU - Reddy, R V
AU  - Reddy RV
AD  - Department of Veterinary Biomedical Sciences, College of Veterinary Medicine, 
      University of Missouri, Columbia 659211.
FAU - Reddy, C S
AU  - Reddy CS
FAU - Frappier, B L
AU  - Frappier BL
FAU - Brimer, G E
AU  - Brimer GE
FAU - Fraipier, B L
AU  - Fraipier BL
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Nat Toxins
JT  - Natural toxins
JID - 9212382
RN  - 27YG812J1I (Arachidonic Acid)
RN  - 3G6A5W338E (Caffeine)
RN  - W980KJ009P (Corticosterone)
RN  - YOW8V9698H (Dimethyl Sulfoxide)
SB  - IM
EIN - Nat Toxins 1994;2(4):252
MH  - Abnormalities, Drug-Induced/*pathology
MH  - Animals
MH  - Arachidonic Acid/*toxicity
MH  - Caffeine/*toxicity
MH  - Cleft Palate/chemically induced/pathology
MH  - Corticosterone/blood
MH  - Dimethyl Sulfoxide/*toxicity
MH  - Drug Synergism
MH  - Face/pathology
MH  - Female
MH  - Hematoma/chemically induced/pathology
MH  - Male
MH  - Mice
MH  - Mice, Inbred Strains
MH  - Pregnancy
EDAT- 1994/01/01 00:00
MHDA- 1994/01/01 00:01
CRDT- 1994/01/01 00:00
PHST- 1994/01/01 00:00 [pubmed]
PHST- 1994/01/01 00:01 [medline]
PHST- 1994/01/01 00:00 [entrez]
AID - 10.1002/nt.2620020107 [doi]
PST - ppublish
SO  - Nat Toxins. 1994;2(1):29-35. doi: 10.1002/nt.2620020107.