Abstract
We tested the hypothesis that tumor necrosis factor-α (TNF-α) would be teratogenic in mice due in part to its effects on zinc metabolism. In Experiment 1, nonpregnant mice were injected with a single dose of TNF-α (40,000 U) or PBS and then received a 65Zn-labeled meal. Mice killed 10 h after TNF-α treatment had high liver 65Zn and low plasma 65Zn, compared with controls. In Experiment 2, gestation day 8 (GD 8) mice were injected with PBS or TNF-α and then received a 65Zn-labeled meal. Dams killed 10 h after TNF-α treatment had higher liver and kidney 65Zn and lower plasma and embryonic 65Zn accumulation than controls. In Experiment 3, TNF-α dosing from GD 7-12 was associated with high maternal liver Zn and metallothionein concentrations on GD 13 and a high frequency of exencephaly on GD 18. In Experiment 4, dams fed diets containing 4.5, 12.5 or 50.0 μg Zn/g were given PBS or TNF-α on GD 7-12. Gross fetal defects were not observed in the PBS-treated litters evaluated on GD 18. In contrast, TNF-α- treated litters were characterized by multiple defects, with the incidence and severity being highest in the low Zn diet group. In Experiment 5, embryos cultured in serum from TNF-α-treated animals exhibited a high frequency of defects; the developmental toxicity of this serum was ameliorated when it was supplemented with Zn. Thus, the developmental toxicity of TNF-α is due in part to its influence on Zn metabolism.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 908-919 |
| Number of pages | 12 |
| Journal | Journal of Nutrition |
| Volume | 125 |
| Issue number | 4 |
| State | Published - 1995 |
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Keywords
- development
- metallothionein
- mice
- tumor necrosis factor-α
- zinc
ASJC Scopus subject areas
- Food Science
- Medicine (miscellaneous)
Cite this
Tumor necrosis factor-α alters maternal and embryonic zinc metabolism and is developmentally toxic in mice. / Taubeneck, M. W.; Daston, G. P.; Rogers, J. M.; Gershwin, M. Eric; Ansari, A.; Keen, Carl L.
In: Journal of Nutrition, Vol. 125, No. 4, 1995, p. 908-919.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Tumor necrosis factor-α alters maternal and embryonic zinc metabolism and is developmentally toxic in mice
AU - Taubeneck, M. W.
AU - Daston, G. P.
AU - Rogers, J. M.
AU - Gershwin, M. Eric
AU - Ansari, A.
AU - Keen, Carl L
PY - 1995
Y1 - 1995
N2 - We tested the hypothesis that tumor necrosis factor-α (TNF-α) would be teratogenic in mice due in part to its effects on zinc metabolism. In Experiment 1, nonpregnant mice were injected with a single dose of TNF-α (40,000 U) or PBS and then received a 65Zn-labeled meal. Mice killed 10 h after TNF-α treatment had high liver 65Zn and low plasma 65Zn, compared with controls. In Experiment 2, gestation day 8 (GD 8) mice were injected with PBS or TNF-α and then received a 65Zn-labeled meal. Dams killed 10 h after TNF-α treatment had higher liver and kidney 65Zn and lower plasma and embryonic 65Zn accumulation than controls. In Experiment 3, TNF-α dosing from GD 7-12 was associated with high maternal liver Zn and metallothionein concentrations on GD 13 and a high frequency of exencephaly on GD 18. In Experiment 4, dams fed diets containing 4.5, 12.5 or 50.0 μg Zn/g were given PBS or TNF-α on GD 7-12. Gross fetal defects were not observed in the PBS-treated litters evaluated on GD 18. In contrast, TNF-α- treated litters were characterized by multiple defects, with the incidence and severity being highest in the low Zn diet group. In Experiment 5, embryos cultured in serum from TNF-α-treated animals exhibited a high frequency of defects; the developmental toxicity of this serum was ameliorated when it was supplemented with Zn. Thus, the developmental toxicity of TNF-α is due in part to its influence on Zn metabolism.
AB - We tested the hypothesis that tumor necrosis factor-α (TNF-α) would be teratogenic in mice due in part to its effects on zinc metabolism. In Experiment 1, nonpregnant mice were injected with a single dose of TNF-α (40,000 U) or PBS and then received a 65Zn-labeled meal. Mice killed 10 h after TNF-α treatment had high liver 65Zn and low plasma 65Zn, compared with controls. In Experiment 2, gestation day 8 (GD 8) mice were injected with PBS or TNF-α and then received a 65Zn-labeled meal. Dams killed 10 h after TNF-α treatment had higher liver and kidney 65Zn and lower plasma and embryonic 65Zn accumulation than controls. In Experiment 3, TNF-α dosing from GD 7-12 was associated with high maternal liver Zn and metallothionein concentrations on GD 13 and a high frequency of exencephaly on GD 18. In Experiment 4, dams fed diets containing 4.5, 12.5 or 50.0 μg Zn/g were given PBS or TNF-α on GD 7-12. Gross fetal defects were not observed in the PBS-treated litters evaluated on GD 18. In contrast, TNF-α- treated litters were characterized by multiple defects, with the incidence and severity being highest in the low Zn diet group. In Experiment 5, embryos cultured in serum from TNF-α-treated animals exhibited a high frequency of defects; the developmental toxicity of this serum was ameliorated when it was supplemented with Zn. Thus, the developmental toxicity of TNF-α is due in part to its influence on Zn metabolism.
KW - development
KW - metallothionein
KW - mice
KW - tumor necrosis factor-α
KW - zinc
UR - http://www.scopus.com/inward/record.url?scp=0028987451&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0028987451&partnerID=8YFLogxK
M3 - Article
C2 - 7722694
AN - SCOPUS:0028987451
VL - 125
SP - 908
EP - 919
JO - Journal of Nutrition
JF - Journal of Nutrition
SN - 0022-3166
IS - 4
ER -