title: Biliary excretion of exogenous cadmium, and endogenous copper and zinc in the Eisai hyperbilirubinuric (EHB) rat with a near absence of biliary glutathione.
abstract: Mutant Eisai hyperbilirubinuric (EHB) rats derived from an inbred strain of Sprague-Dawley (SD) rats are characterized by a near absence of biliary excretion of glutathione (GSH) due to inherently impaired ATP-driven organic anion transport. Cd (0.1 mg/kg bw from CdCl2) was injected intravenously into EHB rats and control SD rats. Output of biliary excretion of Cd was followed over 15-min intervals up to 60 min. Cd was excreted rapidly and reached the maximum level (73.2 ng/15 min) in the period from 15 to 30 min in SD rats. Its excretion in EHB rats, however was one-fortieth (only 1.8 ng/15 min) of that in SD rats. Biliary concentrations of two endogenous metals, Cu and Zn were also measured. The output of Cu in EHB rat bile (50 ng/15 min before Cd injection) was about one-fifth of that in SD rat bile (270 ng/15 min). The output was not influenced by the Cd injection in the two groups. There was a slight difference of Zn output between the two groups. The biliary excretion of GSH was 500 to 700 micrograms/15 min and only 1 to 2 micrograms/15 min in SD and EHB rats, respectively. Sixty min after Cd injection, the Cd concentrations in the serum, liver and kidney were slightly higher in EHB rats than in SD rats. There was no difference in the hepatic metallothionein (MT-I and-II) concentration between SD (34 micrograms/g liver) and EHB (33 micrograms/g liver) rats. The renal Cu concentration was about four times in the higher in the EHB rat than in the SD rat. These results suggest that reduced biliary excretion of Cd is mainly, but that of Cu is only partly, based in reduced canalicular transport of GSH due to lack of an ATP-driven organic anion transport system, not MT induction in EHB rats. It seems likely that biliary excretion of Cd is regulated mainly by the canalicular anion transport in rats.
authors.affiliation: Department of Public Health, Sapporo Medical University, Japan.
authors.forename: N
authors.initials: N
authors.lastname: Sugawara
authors.forename: Y R
authors.initials: YR
authors.lastname: Lai
authors.forename: K
authors.initials: K
authors.lastname: Arizono
authors.forename: T
authors.initials: T
authors.lastname: Ariyoshi
mesh_terms: D000255:Adenosine Triphosphate / Q000494:pharmacology; D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood; D001646:Bile / Q000378:metabolism*; D002104:Cadmium / Q000008:administration & dosage / Q000097:blood / Q000378:metabolism / Q000493:pharmacokinetics* / Q000633:toxicity; D019256:Cadmium Chloride; D002273:Carcinogens / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000633:toxicity; D002712:Chlorides / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000633:toxicity; D003300:Copper / Q000378:metabolism*; D004797:Enzyme-Linked Immunosorbent Assay; D005978:Glutathione / Q000378:metabolism; D006932:Hyperbilirubinemia / Q000097:blood / Q000378:metabolism*; D007275:Injections, Intravenous; D017136:Ion Transport / Q000187:drug effects; D007668:Kidney / Q000187:drug effects / Q000378:metabolism; D007770:L-Lactate Dehydrogenase / Q000097:blood; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008668:Metallothionein / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013047:Specific Pathogen-Free Organisms; D014018:Tissue Distribution; D015032:Zinc / Q000378:metabolism*
chemical_list: D002273:Carcinogens; D002712:Chlorides; D002104:Cadmium; D003300:Copper; D000255:Adenosine Triphosphate; D008668:Metallothionein; D007770:L-Lactate Dehydrogenase; D001219:Aspartate Aminotransferases; D005978:Glutathione; D015032:Zinc; D019256:Cadmium Chloride