Jejunal transfer rates of 109cadmium chloride increase in rats in vitro and in vivo after oral pretreatment with cadmium or zinc chloride.
An increased body retention of Cd in rats orally pretreated with Cd or Zn is explained by induction of hepatic and renal metallothionein. Whether intestinal absorption of Cd increases after such treatments is not clear yet. To approach this problem we measured jejunal transfer rates of 109Cd in vitro and in vivo in pretreated rats (0.44 mmol Cd/l or 4.6 mmol Zn/l in the drinking water for 10 days) and compared them with those of untreated controls. Isolated jejunal segments were used for in vitro perfusion. In vivo perfusion was performed in anaesthetized rats with blood collected from mesenteric venules substituting corresponding losses by reinfusion of rat blood. Water and glucose transfer did not differ between controls and pretreated rats. At a luminal concentration of 5 micromol 109CdCl2/l, Cd and Zn pretreatment significantly increased the transfer rate of 109Cd in vitro and in vivo similarly. The 109Cd transfer rates in controls in the final perfusion intervals (80-120 min) were 0.06 (pmol/cm/min) in vivo and 0.05 in vitro; the corresponding rates in Cd or Zn pretreated rats were significantly higher (P<0.05) and amounted to 0.11 and 0.18 or 0.15 and 0.23, respectively. Mucosal concentrations of 109Cd measured at the end of the perfusion period tended to be lower in the pretreated animals than in the controls. This suggests that pretreatment with Cd or Zn reduces the amount of 109Cd bound to the tissue leaving more 109Cd for the transfer step. As compared to a level of mucosal metallothionein of 8 microg/g wet weight in controls, increased amounts of 67 or 52 microg/g wet weight in the Cd or Zn pretreated rats, respectively, thus did not decrease but increased transfer rates of 109Cd. Therefore, increased small intestinal transfer rates of Cd can contribute to increase the body retention of Cd seen after oral pretreatment with Cd or Zn.
Flaig
Karl-Heinz
KH
Walther Straub-Institut für Pharmakologie und Toxikologie, Ludwig-Maximilians-Universität, Nussbaumstr. 26, D-80336 München, Germany.
Schümann
Klaus
K
Elsenhans
Bernd
B
D000818:Animals; D002104:Cadmium / Q000097:blood / Q000493:pharmacokinetics*; D019256:Cadmium Chloride / Q000494:pharmacology*; D002106:Cadmium Radioisotopes; D002712:Chlorides / Q000494:pharmacology*; D002850:Chromatography, Gel; D005260:Female; D066298:In Vitro Techniques; D007408:Intestinal Absorption / Q000187:drug effects; D007413:Intestinal Mucosa / Q000187:drug effects / Q000378:metabolism; D007583:Jejunum / Q000187:drug effects* / Q000378:metabolism*; D008668:Metallothionein / Q000502:physiology; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D017967:Zinc Compounds / Q000494:pharmacology*
D002106:Cadmium Radioisotopes; D002712:Chlorides; D017967:Zinc Compounds; D002104:Cadmium; C016837:zinc chloride; D008668:Metallothionein; D019256:Cadmium Chloride