Reversible and persistent consequences of copper deficiency in developing mice.
The effect of maternal copper (Cu) deficiency on various proteins was studied to determine if the changes were reversible or persistent with Cu repletion. The functional consequences of these alterations were assessed by exposing the animals to an oxidative stress (endotoxin), and by measuring the formation of benzo[a]pyrene-DNA adducts in vitro. Throughout gestation and lactation, mice were fed a Control diet (10 micrograms Cu/g diet) or a Low Cu diet (1 microgram Cu/g diet). On day 18, the offspring were killed or switched to the Control diet and killed on day 42 following a single injection of saline or endotoxin on day 41. In day-18 offspring, Cu deficiency resulted in decreased hematocrit values, ceruloplasmin activity, liver and tissue Cu levels, and metallothionein concentrations. Cu repletion restored all but metallothionein levels. Early Cu deficiency led to higher brain CuZn superoxide dismutase activity on day 42, and higher levels of brain thiobarbituric acid reactive substances (TBARS) in endotoxin-treated mice. Liver TBARS were lower in day-18 Low Cu offspring and in day-42 Low Cu offspring treated with endotoxin than age-matched Controls. Cytochrome P-450 concentrations were lower in Low Cu, endotoxin-treated males than in Controls. These results show that Cu deficiency-mediated alterations during early development are not immediately reversed with Cu repletion.
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Biochemical Research and Development, Miles Inc, Berkeley, CA 94701.
Keen
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D015660:7-Alkoxycoumarin O-Dealkylase / Q000378:metabolism; D000818:Animals; D001564:Benzo(a)pyrene / Q000378:metabolism; D001835:Body Weight; D001921:Brain / Q000378:metabolism; D002570:Ceruloplasmin / Q000378:metabolism; D003300:Copper / Q000172:deficiency* / Q000378:metabolism; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D005314:Embryonic and Fetal Development; D005260:Female; D006400:Hematocrit; D006454:Hemoglobins / Q000378:metabolism; D007668:Kidney / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D008668:Metallothionein / Q000378:metabolism; D051379:Mice; D008815:Mice, Inbred Strains; D009929:Organ Size; D011247:Pregnancy; D011248:Pregnancy Complications / Q000378:metabolism*; D013482:Superoxide Dismutase / Q000378:metabolism; D013858:Thiobarbiturates / Q000378:metabolism; D014131:Trace Elements / Q000378:metabolism
D006454:Hemoglobins; D013858:Thiobarbiturates; D014131:Trace Elements; D001564:Benzo(a)pyrene; D003300:Copper; D003577:Cytochrome P-450 Enzyme System; D008668:Metallothionein; D015660:7-Alkoxycoumarin O-Dealkylase; D013482:Superoxide Dismutase; D002570:Ceruloplasmin; C029684:thiobarbituric acid