Transport of N-acetyl-S-pentachloro-1,3-butadienylcysteine by rat renal cortex

N-acetyl-S-pentachloro-1,3-butadienyl-L-cysteine (PCBD-NAC) is a postulated metabolite derived from glutathione conjugation of hexachloro-1,3-butadiene and is nephrotoxic in the rat. Because PCBD-NAC causes selective necrosis to the pars recta of the proximal tubule, and is an organic anion it might...

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Bibliographic Details
Published in:Archives of toxicology 1986-05, Vol.59 (1), p.12-15
Main Authors: LOCK, E. A, ODUM, J, ORMOND, P
Format: Article
Language:English
Subjects:
Acetylcysteine - analogs & derivatives
Animals
Antimetabolites - pharmacology
Biological and medical sciences
Biological Transport, Active
Butadienes - metabolism
Chemical and industrial products toxicology. Toxic occupational diseases
Cysteine - analogs & derivatives
Cysteine - metabolism
Female
Kidney Cortex - metabolism
Kinetics
Medical sciences
Rats
Rats, Inbred Strains
Temperature
Toxicology
Various organic compounds
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Summary:N-acetyl-S-pentachloro-1,3-butadienyl-L-cysteine (PCBD-NAC) is a postulated metabolite derived from glutathione conjugation of hexachloro-1,3-butadiene and is nephrotoxic in the rat. Because PCBD-NAC causes selective necrosis to the pars recta of the proximal tubule, and is an organic anion it might be expected to be transported by the renal organic anion transport system. Rat renal cortical slices were used to characterise the transport. 14C-PCBD-NAC uptake was temperature dependent and reduced by the metabolic inhibitors cyanide and iodoacetate. Probenecid and sulphinpyrazone, specific competitive inhibitors of the anion transport system, and dinitrophenol, a metabolic inhibitor as well as a competitive inhibitor of anion transport, reduced PCBD-NAC transport. Organic cations or uric acid transport inhibitors did not alter PCBD-NAC accumulation by the slices. These data are consistent with the transport of PCBD-NAC by the renal organic anion secretory system.
ISSN:0340-5761
1432-0738
DOI:10.1007/BF00263950