PMID: 3762309Oct 6, 1986Paper

Deuterium isotope effect in acute N-(3,5-dichlorophenyl)succinimide-induced nephrotoxicity

Life Sciences
G O RankinP I Brown

Abstract

Deuterium labelling of the succinimide ring of N-(3,5-dichlorophenyl) succinimide (NDPS) markedly reduced the acute nephrotoxicity produced by NDPS administration to Fischer 344 rats. Administration of the deuterium-labelled derivative, NDPS-d4, to male Fischer 344 rats failed to produce the marked diuresis, increased proteinuria, glucosuria, hematuria, elevated blood urea nitrogen (BUN) concentration and kidney weight, decreased basal p-aminohippurate (PAH) accumulation, and proximal tubular necrosis which are characteristic of NDPS-induced nephrotoxicity. However, lactate-stimulated PAH and tetraethylammonium (TEA) accumulation were decreased by NDPS-d4 (1.0 mmol/kg). The lack of nephrotoxicity produced by NDPS-d4 suggests that oxidation at the carbon-carbon bridge of the succinimide ring is an important biotransformation step in the generation of the nephrotoxic species of NDPS.

References

Jan 1, 1979·Pharmacology & Therapeutics. Part B: General & Systematic Pharmacology·J Diézi, J Biollaz
Feb 1, 1986·Toxicology Letters·G O RankinP I Brown
Jan 1, 1985·Toxicology Letters·G O RankinP I Brown
Dec 1, 1985·Fundamental and Applied Toxicology : Official Journal of the Society of Toxicology·D J YangG O Rankin
Nov 20, 1966·Journal of the American Chemical Society·S G CohenS Y Weinstein
Mar 15, 1981·Toxicology and Applied Pharmacology·W M Kluwe

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Citations

Jun 1, 1992·Journal of Applied Toxicology : JAT·G O RankinJ L Hubbard
Feb 15, 1988·Biochemical Pharmacology·M ValentovicG O Rankin
Oct 12, 2001·Journal of Toxicology and Environmental Health. Part a·S K HongG O Rankin
Apr 10, 2002·Journal of Toxicology and Environmental Health. Part a·Gary O RankinPatrick I Brown
Apr 18, 2008·Journal of Applied Toxicology : JAT·Gary O RankinDianne K Anestis
Dec 1, 1988·Toxicology and Applied Pharmacology·G O RankinP I Brown
Jun 1, 1987·Journal of Applied Toxicology : JAT·D J YangG O Rankin
Aug 1, 1989·Journal of Applied Toxicology : JAT·G O RankinP I Brown
Apr 1, 1996·Xenobiotica; the Fate of Foreign Compounds in Biological Systems·R I GriffinP J Harvison

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