Partial contribution of biliary metabolites to nephrotoxicity, renal content and excretion of [14C]hexachloro-1,3-butadiene in rats. 1993

J P Payan, and D Beydon, and J P Fabry, and G Morel, and M T Brondeau, and M Ban, and J De Ceaurriz
Institut National de Recherche et de Sécurité, Vandoeuvre, France.

Male Sprague Dawley rats with cannulated bile duct (BDC rats) received 100 or 200 mg kg-1 labelled hexachloro-1,3-butadiene ([14C]HCBD) by gavage 1 h (BDC1 rats) or 24 h (BDC24 rats) after surgical cannula implantation. Twenty-four hours after treatment with HCBD, rats were examined histochemically and biochemically for kidney damage. Urine, faeces, liver and kidney radioactivities were also measured in 24-h samples. Results were compared with those obtained from non-cannulated (NC) rats. Bile-duct cannulation did not completely protect against HCBD-induced kidney damage. The 24-h [14C] urinary excretion and tissue content was 30-50% lower in BDC rats compared to NC rats and correlated well with the toxicity findings. BDC1 rats appeared to be much more resistant to HCBD treatment than BDC24 rats. Since faecal [14C] radioactivity extractable by diethyl ether at neutral pH in BDC1 rats was twice that measured in BDC24 rats, the greater resistance was attributed to a higher deficiency in the gastrointestinal absorption of unchanged HCBD. The present results reveal that the biliary metabolites of HCBD are not solely responsible for kidney toxicity as previously assumed. They suggest a sinusoidal efflux of the HCBD conjugates from the liver.

UI MeSH Term Description Entries
D007668 Kidney Body organ that filters blood for the secretion of URINE and that regulates ion concentrations. Kidneys
D007674 Kidney Diseases Pathological processes of the KIDNEY or its component tissues. Disease, Kidney,Diseases, Kidney,Kidney Disease
D008099 Liver A large lobed glandular organ in the abdomen of vertebrates that is responsible for detoxification, metabolism, synthesis and storage of various substances. Livers
D008297 Male Males
D010084 Oxidation-Reduction A chemical reaction in which an electron is transferred from one molecule to another. The electron-donating molecule is the reducing agent or reductant; the electron-accepting molecule is the oxidizing agent or oxidant. Reducing and oxidizing agents function as conjugate reductant-oxidant pairs or redox pairs (Lehninger, Principles of Biochemistry, 1982, p471). Redox,Oxidation Reduction
D002070 Butadienes Four carbon unsaturated hydrocarbons containing two double bonds. Butadiene Derivative,Butadiene Derivatives,Derivative, Butadiene,Derivatives, Butadiene
D002406 Catheterization, Peripheral Insertion of a catheter into a peripheral artery, vein, or airway for diagnostic or therapeutic purposes. Arterial Catheterization, Peripheral,Catheterization, Bronchial,Catheterization, Peripheral Arterial,Catheterization, Peripheral Venous,Peripheral Catheterization,Venous Catheterization, Peripheral,Bronchial Catheterization,PICC Line Catheterization,PICC Line Placement,PICC Placement,Peripheral Arterial Catheterization,Peripheral Venous Catheterization,Peripherally Inserted Central Catheter Line Insertion,Arterial Catheterizations, Peripheral,Bronchial Catheterizations,Catheterization, PICC Line,Catheterizations, Bronchial,Catheterizations, PICC Line,Catheterizations, Peripheral,Catheterizations, Peripheral Arterial,Catheterizations, Peripheral Venous,PICC Line Catheterizations,PICC Line Placements,PICC Placements,Peripheral Arterial Catheterizations,Peripheral Catheterizations,Peripheral Venous Catheterizations,Placement, PICC,Placement, PICC Line,Placements, PICC,Placements, PICC Line,Venous Catheterizations, Peripheral
D003135 Common Bile Duct The largest bile duct. It is formed by the junction of the CYSTIC DUCT and the COMMON HEPATIC DUCT. Choledochus,Bile Duct, Common,Common Bile Ducts,Duct, Common Bile
D005659 Fungicides, Industrial Chemicals that kill or inhibit the growth of fungi in agricultural applications, on wood, plastics, or other materials, in swimming pools, etc. Industrial Fungicides
D005978 Glutathione A tripeptide with many roles in cells. It conjugates to drugs to make them more soluble for excretion, is a cofactor for some enzymes, is involved in protein disulfide bond rearrangement and reduces peroxides. Reduced Glutathione,gamma-L-Glu-L-Cys-Gly,gamma-L-Glutamyl-L-Cysteinylglycine,Glutathione, Reduced,gamma L Glu L Cys Gly,gamma L Glutamyl L Cysteinylglycine

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