Cadmium absorption and its relationship to divalent metal transporter-1 in the pregnant rat.
Increased intestinal absorption of essential nutrients is characteristic of pregnancy as the maternal gastrointestinal tract undergoes physiological and biochemical changes to accommodate the increased demand for essential nutrients by the fetus. Divalent metal transporter-1 (DMT-1) is primarily responsible for dietary iron uptake in the duodenum but also recognizes nonessential metals such as cadmium (Cd). Increased absorption of Cd has been reported in pregnant compared with nonpregnant mice; however, the mechanism is not understood. The purpose of this work was to determine whether Cd absorption is increased in pregnant compared with nonpregnant rats and whether this correlates with a time-dependent up-regulation of DMT-1 expression. Timed pregnant and nonpregnant female Sprague-Dawley rats were administered (109)Cd-labeled CdCl(2) by oral gavage on gestation day (gd) 19. Tissues were collected on gd 20 for (109)Cd assessment (values expressed as pmol Cd). Greater accumulation of (109)Cd was observed in duodenum than in jejunum and ileum in both pregnant and nonpregnant rats. However, the amount of Cd in small intestine was higher in pregnant than nonpregnant rats. Additionally, more Cd accumulated in the liver and kidney of pregnant than nonpregnant rats. DMT-1 mRNA levels were determined in duodenum, placenta, liver, and kidney with branched DNA signal amplification. DMT-1 mRNA levels were about sixfold higher in duodenum of (gd 21) pregnant than nonpregnant rats and the levels in pregnant rats increased from gd 15 through gd 21. The correlation between Cd absorption and DMT-1 expression observed in pregnant rats suggests a role for DMT-1 in the increased absorption of Cd during pregnancy.
Leazer
Tyra M
TM
Department of Pharmacology, Toxicology and Therapeutics, University of Kansas Medical Center, Kansas City, Kansas 66160, USA.
Liu
Yaping
Y
Klaassen
Curtis D
CD
D000818:Animals; D002104:Cadmium / Q000493:pharmacokinetics*; D027682:Cation Transport Proteins / Q000235:genetics*; D004386:Duodenum / Q000378:metabolism; D005260:Female; D005786:Gene Expression Regulation; D007408:Intestinal Absorption; D033862:Iron-Binding Proteins / Q000235:genetics*; D007668:Kidney / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D010920:Placenta / Q000378:metabolism; D011247:Pregnancy; D011270:Pregnancy, Animal / Q000378:metabolism*; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D000099236:Solute Carrier Family 11, Member 2
D002104:Cadmium; D027682:Cation Transport Proteins; D033862:Iron-Binding Proteins; D012333:RNA, Messenger; D000099236:Solute Carrier Family 11, Member 2