PMID- 1981536
OWN - NLM
STAT- MEDLINE
DCOM- 19910415
LR  - 20141120
IS  - 0090-9556 (Print)
IS  - 0090-9556 (Linking)
VI  - 18
IP  - 6
DP  - 1990 Nov-Dec
TI  - Metabolism of hexafluoropropene. Evidence for bioactivation by glutathione 
      conjugate formation in the kidney.
PG  - 911-6
AB  - We investigated the metabolism of hexafluoropropene, a nephrotoxic fluoroalkene, 
      in rat liver and kidney subcellular fractions and in rats in vivo. Incubation of 
      hexafluoropropene (1 mM) with microsomes and cytosol in the presence of 
      glutathione (GSH) yielded S-(1,2,3,3,3-pentafluoropropenyl)glutathione (PPFG) and 
      S-(1,1,2,3,3,3-hexafluoropropyl)glutathione (HFPG) as identified by thermospray 
      mass spectrometry and 1H-NMR. In liver microsomes, PFPG formation was predominant 
      (240 nmol/min/mg protein) over HFPG (36 nmol/min/mg), whereas in cytosol, HFPG 
      was the only hexafluoropropene metabolite (136 nmol/min/mg) detectable. In kidney 
      microsomes, GSH-conjugate formation could not be detected; in kidney cytosol, 
      HFPG was exclusively formed (46 nmol/min/mg). Hexafluoropropene inhalation (800 
      ppm for 1 hr) in rats fitted with a biliary cannula resulted in the biliary 
      elimination of PFPG without detectable formation of HFPG; the exclusively formed 
      urinary metabolite, identified by GC/MS, was 
      N-acetyl-S-(1,1,2,3,3,3-hexafluoropropy)-L-cysteine. The results show that 
      hexafluoropropene is metabolized to two different GSH-conjugates in rat liver and 
      kidney. The data also suggest that hexafluoropropene metabolites formed in the 
      liver and eliminated with bile are not translocated to the kidney and that 
      intrarenal bioactivation by GSH-conjugation may be responsible for 
      hexafluoropropene-induced nephrotoxicity.
FAU - Koob, M
AU  - Koob M
AD  - Institut fur Toxikologie, Universitat Wurzburg, FRG.
FAU - Dekant, W
AU  - Dekant W
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Drug Metab Dispos
JT  - Drug metabolism and disposition: the biological fate of chemicals
JID - 9421550
RN  - 0 (Fluorocarbons)
RN  - 116-15-4 (hexafluoropropene)
RN  - GAN16C9B8O (Glutathione)
SB  - IM
MH  - Animals
MH  - Biotransformation
MH  - Chromatography, High Pressure Liquid
MH  - Female
MH  - Fluorocarbons/*metabolism
MH  - Glutathione/*metabolism
MH  - In Vitro Techniques
MH  - Kidney/*metabolism
MH  - Liver/metabolism
MH  - Rats
MH  - Rats, Inbred Strains
MH  - Spectrophotometry, Ultraviolet
MH  - Subcellular Fractions/metabolism
EDAT- 1990/11/01 00:00
MHDA- 1990/11/01 00:01
CRDT- 1990/11/01 00:00
PHST- 1990/11/01 00:00 [pubmed]
PHST- 1990/11/01 00:01 [medline]
PHST- 1990/11/01 00:00 [entrez]
PST - ppublish
SO  - Drug Metab Dispos. 1990 Nov-Dec;18(6):911-6.