PMID- 11786231
OWN - NLM
STAT- MEDLINE
DCOM- 20020306
LR  - 20191227
IS  - 0006-3002 (Print)
IS  - 0006-3002 (Linking)
VI  - 1568
IP  - 3
DP  - 2001 Dec 19
TI  - Reoxygenation after cold hypoxic storage of cultured precision-cut rat liver 
      slices: effects on cellular metabolism and drug biotransformation.
PG  - 245-51
AB  - Cultured rat precision-cut liver slices (PCLS) were used to study the influence 
      of hypothermic preservation and reoxygenation at 37 degrees C on cellular 
      metabolism and drug biotransformation. Cold hypoxic storage caused a depressed 
      metabolism in rat liver slices, but reoxygenation for 8 h at 37 degrees C 
      partially restored the levels of both ATP and GSH and totally restored the 
      capacity to synthesize proteins. Metabolism of midazolam (CYP3A-dependent 
      oxidation) by cold preserved liver slices was decreased by 30% but no further 
      affected by reoxygenation, showing the same profile as freshly cut slices. Such a 
      reoxygenation at 37 degrees C is accompanied by a dramatic loss of CYP3A2 protein 
      while CYP3A1 protein was unaffected. These results suggest that CYP3A2 did not 
      play a major role in midazolam oxidation. Such results are not consistent with a 
      putative reoxygenation injury but rather with cold hypoxic damage. Since cold 
      preserved liver slices did not respond to bacterial endotoxin stimulation 
      (lipopolysaccharides), a minor role of non-parenchymal cells is suggested as 
      mediators for deleterious effects developed during the cold storage.
FAU - Rekka, E
AU  - Rekka E
AD  - Unite de Pharmacocinetique, Metabolisme, Nutrition et Toxicologie, Departement de 
      Sciences Pharmaceutiques, Universite Catholique de Louvain, Louvain, Belgium.
FAU - Evdokimova, E
AU  - Evdokimova E
FAU - Eeckhaudt, S
AU  - Eeckhaudt S
FAU - Calderon, P B
AU  - Calderon PB
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - Netherlands
TA  - Biochim Biophys Acta
JT  - Biochimica et biophysica acta
JID - 0217513
RN  - 0 (Lipopolysaccharides)
RN  - 8L70Q75FXE (Adenosine Triphosphate)
RN  - 9035-51-2 (Cytochrome P-450 Enzyme System)
RN  - EC 1.14.- (Steroid Hydroxylases)
RN  - EC 1.14.14.1 (Aryl Hydrocarbon Hydroxylases)
RN  - EC 1.14.14.1 (Cyp3a23-3a1 protein, rat)
RN  - EC 1.14.14.1 (Cytochrome P-450 CYP3A)
RN  - EC 1.14.14.1 (steroid hormone 6-beta-hydroxylase)
RN  - GAN16C9B8O (Glutathione)
RN  - R60L0SM5BC (Midazolam)
RN  - S88TT14065 (Oxygen)
SB  - IM
MH  - Adenosine Triphosphate/analysis
MH  - Animals
MH  - *Aryl Hydrocarbon Hydroxylases
MH  - Biotransformation
MH  - Cold Temperature
MH  - *Cryopreservation
MH  - Cytochrome P-450 CYP3A
MH  - Cytochrome P-450 Enzyme System/analysis
MH  - Energy Metabolism
MH  - Glutathione/analysis
MH  - Lipopolysaccharides
MH  - *Liver
MH  - Male
MH  - Midazolam/chemistry
MH  - Oxidation-Reduction
MH  - *Oxygen
MH  - Rats
MH  - Rats, Wistar
MH  - Steroid Hydroxylases/analysis
MH  - Time Factors
EDAT- 2002/01/12 10:00
MHDA- 2002/03/07 10:01
CRDT- 2002/01/12 10:00
PHST- 2002/01/12 10:00 [pubmed]
PHST- 2002/03/07 10:01 [medline]
PHST- 2002/01/12 10:00 [entrez]
AID - S0304416501002252 [pii]
AID - 10.1016/s0304-4165(01)00225-2 [doi]
PST - ppublish
SO  - Biochim Biophys Acta. 2001 Dec 19;1568(3):245-51. doi: 
      10.1016/s0304-4165(01)00225-2.