Lack of biliary excretion of Cd linked to an inherent defect of the canalicular isoform of multidrug resistance protein (cMrp) does not abnormally stimulate accumulation of Cd in the Eisai hyperbilirubinemic (EHB) rat liver.
A new mutant, the Eisai hyperbilirubinemic (EHB) rat, shows no inherent expression of the canalicular isoform of the multidrug resistance protein (cMrp) in the liver. It has defective biliary secretion of organic anions such as bilirubin glucuronides, bromosulfophthalein (BSP), cysteinyl leukotrienes, glutathione (GSH) and bile acid sulfate and glucuronides. When rats were injected intravenously with CdCl2, biliary excretion of Cd over 30 min was 0.28% and 0.004% of the total dose in Sprague-Dawley (SD) and EHB rats, respectively. Six SD rats and five EHB rats were fed a diet containing Cd. Bile Cd was detected at the level of 2 ng/20 min in SD rats, but not in EHB rats. There was no significant difference of hepatic Cd concentration between SD and EHB rats. Furthermore, there were no significant differences of renal and intestinal Cd, and hepatic and renal metallothionein (MT) concentrations between the SD and EHB groups. Biliary excretion of reduced-GSH for 20 min was 1.3 +/- 0.3 mg and 3.6 +/- 0.9 micrograms in SD and EHB rats, respectively. Our results suggest that hepatobiliary excretion of exogenous Cd is mediated mainly via carrier transport, including a cMrp or GSH carrier, but that the lack of the transport pathway does not contribute to abnormal accumulation of Cd in the liver.
Sugawara
N
N
Department of Public Health, Sapporo Medical University, Japan.
Lai
Y R
YR
Arizono
K
K
Kitajima
T
T
Inoue
H
H
D000117:Acetylglucosamine / Q000378:metabolism; D000818:Animals; D001646:Bile / Q000378:metabolism*; D001648:Bile Canaliculi / Q000378:metabolism*; D001663:Bilirubin / Q000097:blood; D001692:Biological Transport; D002104:Cadmium / Q000097:blood / Q000378:metabolism*; D018432:Drug Resistance, Multiple; D005978:Glutathione / Q000378:metabolism; D006932:Hyperbilirubinemia / Q000378:metabolism*; D007413:Intestinal Mucosa / Q000378:metabolism; D007668:Kidney / Q000378:metabolism; D008099:Liver / Q000201:enzymology / Q000378:metabolism*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D005723:gamma-Glutamyltransferase / Q000378:metabolism
D002104:Cadmium; D005723:gamma-Glutamyltransferase; D005978:Glutathione; D001663:Bilirubin; D000117:Acetylglucosamine