Fetal zinc deficiency as a mechanism for cadmium induced toxicity to the developing rat lung and pulmonary surfactant.
Maternal exposure to cadmium alters lung and pulmonary surfactant development in the rat fetus. A toxic property of cadmium is its biological interaction with the essential trace metal zinc. The present study was undertaken to determine the role of zinc in the induction of fetal anomalies by cadmium. Pregnant rats were injected with 8 mg/kg cadmium chloride alone or with 12 mg/kg zinc chloride on gestation days 12-15 and sacrificed on gestation day 21. Controls received injections of saline and zinc chloride. Pulmonary surfactant phospholipids were isolated from fetal lungs and quantified. Concentrations of cadmium and zinc in maternal and fetal tissues and placenta were measured. Cadmium treatment caused embryonic death, lung hypoplasia and diminished quantity of the major pulmonary surfactant phospholipid, phosphatidylcholine. Zinc treatment alone did not alter normal fetal development. Coadministration of zinc with cadmium prevented all of the previously observed cadmium-induced fetotoxicity. The placenta appeared to act as a barrier to cadmium movement, as cadmium was found in the placenta but not in fetal tissues. However, cadmium treatment decreased fetal zinc content. Simultaneous injection of zinc with cadmium maintained the fetal zinc concentration at the control level. Thus cadmium appears to exert its fetotoxic effects indirectly, through a fetal zinc deficiency.
D000818:Animals; D001835:Body Weight / Q000187:drug effects; D002105:Cadmium Poisoning / Q000196:embryology* / Q000503:physiopathology; D005260:Female; D005315:Fetal Diseases / Q000503:physiopathology*; D008168:Lung / Q000196:embryology* / Q000378:metabolism; D009929:Organ Size / Q000187:drug effects; D010713:Phosphatidylcholines / Q000378:metabolism; D011247:Pregnancy; D011663:Pulmonary Surfactants / Q000378:metabolism*; D051381:Rats; D013109:Sphingomyelins / Q000378:metabolism; D015032:Zinc / Q000172:deficiency*
D010713:Phosphatidylcholines; D011663:Pulmonary Surfactants; D013109:Sphingomyelins; D015032:Zinc