PMID: 8968194Dec 1, 1996Paper

Cysteine conjugate beta-lyase-dependent biotransformation of the cysteine S-conjugates of the sevoflurane degradation product compound A in human, nonhuman primate, and rat kidney cytosol and mitochondria

Anesthesiology
R A Iyer, M W Anders

Abstract

2-(Fluoromethoxy)-1,1,3,3,3-pentafluoro-1-propene (compound A) is a fluorinated alkene formed by the degradation of sevoflurane in the anesthesia circuit. Compound A is toxic to the kidneys in rats and undergoes glutathione-dependent metabolism in vivo. Several nephrotoxic halogenated alkenes also undergo cysteine conjugate beta-lyase-dependent biotransformation. These experiments were designed to test the hypothesis that cysteine S-conjugates of compound A undergo beta-lyase-dependent biotransformation. S-[2-(Fluoromethoxy)-1,1,3,3,3-pentafluoropropyl]-L-cysteine 4, S-[2-(fluoromethoxy)-1,3,3,3-tetrafluoro-1-propenyl]-L-cysteine 5, and S-(2-chloro-1,1,2-trifluoroethyl)-L-cysteine 11 were incubated with rat, human, and nonhuman primate (cynomolgus, rhesus, and marmoset) kidney cytosol and mitochondria. beta-Lyase activity was determined by measuring pyruvate formation. Compound A-derived conjugates 4 and 5 as well as conjugate 11, a positive control, were substrates for cytosolic and mitochondrial beta-lyase from human, nonhuman primate, and rat kidney. For all substrates, beta-lyase activity was highest in the rat and lowest in the human and was higher in cytosol than in mitochondria. Conjugate 11 was a much better substrate t...Continue Reading

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Citations

Apr 16, 2005·Annual Review of Pharmacology and Toxicology·M W Anders
Feb 12, 1998·Anesthesia and Analgesia·T Staacke
Jan 5, 2002·Drugs·B A Gentz, T P Malan
Oct 3, 2006·Current Opinion in Anaesthesiology·P D NelsonR M Jones
Nov 25, 2005·Anesthesiology·Evan D KharaschH Denny Liggitt
Oct 23, 2001·Drug and Chemical Toxicology·J M CataniaA J Gandolfi
Mar 29, 2001·European Journal of Anaesthesiology·C GoetersH Van Aken
May 20, 2003·Best Practice & Research. Clinical Anaesthesiology·Jan A Baum, Harvey J Woehlck
Dec 31, 2005·Toxicological Sciences : an Official Journal of the Society of Toxicology·Evan D KharaschSengkeo Srinouanprachanh

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