Journal Article

The Embryolethality of Lipopolysaccharide in CD-1 and Metallothionein I–II Null Mice: Lack of a Role for Induced Zinc Deficiency or Metallothionein Induction

Tyra M. Leazer, George P. Daston, Carl L. Keen and John M. Rogers

in Toxicological Sciences

Volume 73, issue 2, pages 442-447
Published in print June 2003 | ISSN: 1096-6080
Published online June 2003 | e-ISSN: 1096-0929 | DOI: http://dx.doi.org/10.1093/toxsci/kfg088
The Embryolethality of Lipopolysaccharide in CD-1 and Metallothionein I–II Null Mice: Lack of a Role for Induced Zinc Deficiency or Metallothionein Induction

More Like This

Show all results sharing these subjects:

  • Medical Toxicology
  • Toxicology (Non-medical)

GO

Show Summary Details

Preview

Lipopolysaccharide (LPS) is embryolethal in CD-1 mice. LPS induces metallothionein (MT) via cytokines, including TNF-α, IL-1, and IL-6, which initiate and maintain the acute phase response. Maternal hepatic MT induction in pregnant rats, by diverse toxicants, can result in maternal hypozincemia and subsequent embryonal zinc (Zn) deficiency. We examined the hypothesis that LPS causes embryo toxicity in CD-1 mice via MT induction and subsequent embryo Zn deficiency by (1) determining whether LPS induces maternal hepatic MT and causes Zn redistribution, (2) assessing the effects of maternal Zn supplementation on LPS developmental toxicity, and (3) assessing the role of MT with MT I-II null mice (MTKO). Timed pregnant CD-1 mice were dosed i.p. with LPS (S. typhimurium) (0.05 mg/kg) on gestation day (gd) 9. Zn supplementation was administered on gd 8 (10 mg/kg, pretreatment) or on gd 9 as a cotreatment (5 or 10 mg/kg). MTKO and wild type (WT) mice were dosed with LPS (0.05 or 0.1 mg/kg) on gd 9, and maternal liver MT and Zn and plasma Zn were measured. In CD-1 mice, maternal hepatic MT was elevated 24 h after LPS treatment, and cotreatment with Zn caused further elevation of MT. Maternal hepatic Zn concentrations paralleled hepatic MT concentrations. Maternal plasma Zn on gd 10 showed no consistent effect of LPS treatment or Zn cotreatment on gd 9. Zn pretreatment (10 mg/kg) on gd 8 did not ameliorate LPS embryolethality, while Zn cotreatment (5 or 10 mg/kg) on gd 9 exacerbated the toxicity of LPS. LPS produced a similar incidence of embryolethality in MTKO and WT strains on gd10. Plasma Zn concentrations were similar in both strains, while hepatic Zn concentrations were significantly higher in WT than in the MTKO strain. In conclusion, while LPS can induce maternal hepatic MT and Zn redistribution in CD-1 mice, this does not appear to be a key mechanism leading to LPS embryotoxicity.

Keywords: lipopolysaccharide; embryolethality; metallothionein; metallothionein null mice; zinc deficiency

Journal Article.  4192 words.  Illustrated.

Subjects: Medical Toxicology ; Toxicology (Non-medical)

Full text: subscription required

How to subscribe Recommend to my Librarian

Users without a subscription are not able to see the full content. Please, subscribe or login to access all content.