PMID- 9649612
OWN - NLM
STAT- MEDLINE
DCOM- 19980723
LR  - 20180330
IS  - 0022-3166 (Print)
IS  - 0022-3166 (Linking)
VI  - 128
IP  - 7
DP  - 1998 Jul
TI  - Zinc pretreatment inhibits isotretinoin teratogenicity and induces embryonic 
      metallothionein in CD-1 mice.
PG  - 1239-46
AB  - Isotretinoin (ITR), a teratogen in many species, is associated with increased 
      oxidative stress. Metallothionein (MT) is an important tissue antioxidant whose 
      concentrations are induced by zinc. To study the role of supplemental Zn as an 
      inducer of embryonic MT, we injected pregnant CD-1 mice subcutaneously with 
      saline vehicle, or 20 or 40 mg/kg Zn on gestational day (GD) 6.5. After 48 h, 
      embryonic MT concentrations increased in a dose-related manner (r = 0.64, P < 
      0.05) with Zn treatment. The possible protective role of Zn pretreatment against 
      ITR teratogenicity was investigated in vivo and in vitro. CD-1 mice were 
      pretreated with saline or Zn (20 and 40 mg/kg) on GD 8.5 and 9.5. ITR was 
      administered to both groups of mice via three intragastric intubations of 100 mg 
      ITR/kg at 4 h intervals on GD 10.5. On GD 18.5, Zn pre-treated mice demonstrated 
      decreased ITR-mediated growth retardation, cleft palates and postpartum 
      mortality. A reduction in embryonic MT concentrations was observed in mice 
      exposed to ITR. Mouse embryos cultured on GD 8.5 with an addition of 15 
      micromol/L Zn for 48 h had a sixfold greater MT concentration (688 microg/g 
      protein) than controls. The Zn pretreatment of cultured embryos prevented 
      malformations and lessened growth retardation caused by 24 h exposure to 17 
      micromol/L ITR. These results suggest that Zn-mediated induction of MT in mouse 
      embryos could protect against ITR teratogenicity.
FAU - Blain, D
AU  - Blain D
AD  - School of Dietetics and Human Nutrition, Macdonald Campus of McGill University, 
      Ste. Anne de Bellevue, Quebec, Canada H9X 3V9.
FAU - Kubow, S
AU  - Kubow S
FAU - Chan, H M
AU  - Chan HM
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Nutr
JT  - The Journal of nutrition
JID - 0404243
RN  - 9038-94-2 (Metallothionein)
RN  - EH28UP18IF (Isotretinoin)
RN  - J41CSQ7QDS (Zinc)
SB  - IM
MH  - Abnormalities, Drug-Induced/*prevention & control
MH  - Animals
MH  - Culture Techniques
MH  - Embryo, Mammalian/metabolism
MH  - Female
MH  - Fetus/*metabolism
MH  - Gestational Age
MH  - Isotretinoin/pharmacology/*toxicity
MH  - Metallothionein/*biosynthesis
MH  - Mice
MH  - Pregnancy
MH  - Yolk Sac/metabolism
MH  - Zinc/administration & dosage/metabolism/*therapeutic use
EDAT- 1998/07/03 00:00
MHDA- 1998/07/03 00:01
CRDT- 1998/07/03 00:00
PHST- 1998/07/03 00:00 [pubmed]
PHST- 1998/07/03 00:01 [medline]
PHST- 1998/07/03 00:00 [entrez]
AID - 10.1093/jn/128.7.1239 [doi]
PST - ppublish
SO  - J Nutr. 1998 Jul;128(7):1239-46. doi: 10.1093/jn/128.7.1239.