PMID- 11812639
OWN - NLM
STAT- MEDLINE
DCOM- 20020327
LR  - 20190916
IS  - 0887-2333 (Print)
IS  - 0887-2333 (Linking)
VI  - 16
IP  - 1
DP  - 2002 Feb
TI  - Effects of bacterial endotoxin (lipopolysaccharides) on survival and metabolism 
      of cultured precision-cut rat liver slices.
PG  - 47-54
AB  - The effect of bacterial endotoxin (lipopolysaccharides from Escherichia coli, 
      LPS) on cellular metabolism and drug biotransformation was studied in 
      precision-cut rat liver slices (PCLS). Xenobiotic metabolism by PCLS was assessed 
      by measuring phase I (midazolam hydroxylation) and phase II (paracetamol 
      conjugates) enzyme activities. Nitrites formation was used as an indirect way to 
      assess LPS-mediated activation of nitric oxide synthase (iNOS, type 2). PCLS 
      incubation with various LPS doses results in a dose-dependent formation of 
      nitrites. Such a nitrite formation is decreased by dexamethasone. After 
      incubation of PCLS for 24 h LPS addition did not increase the basal nitrite 
      formation, indicating that cells are not responsive any more. Paracetamol 
      conjugation was unaffected by LPS treatment but midazolam hydroxylation was 
      reduced by more than 50%. Such a loss is not due to cell impairment since neither 
      survival (LDH leakage) nor cellular metabolism (protein synthesis or ATP content) 
      were modified by LPS. Indeed, under defined conditions, namely Williams' medium E 
      and O(2)/CO(2) (95:5), PCLS maintained both ATP and GSH levels and the capacity 
      of hepatocytes to synthesize proteins. In conclusion, the in vitro model of PCLS 
      reproduces the inhibitory effect of LPS on a CYP3A-dependent activity, allowing a 
      mechanistic approach to study cell-cell interactions.
FAU - Evdokimova, E
AU  - Evdokimova E
AD  - Unite de Pharmacocinetique, Metabolisme, Nutrition et Toxicologie, Departement 
      des Sciences Pharmaceutiques, Universite Catholique de Louvain, Brussels, 
      Belgium.
FAU - Taper, H
AU  - Taper H
FAU - Calderon, P Buc
AU  - Calderon PB
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Toxicol In Vitro
JT  - Toxicology in vitro : an international journal published in association with 
      BIBRA
JID - 8712158
RN  - 0 (Lipopolysaccharides)
RN  - 0 (Nitrites)
RN  - 0 (Proteins)
RN  - 31C4KY9ESH (Nitric Oxide)
RN  - 362O9ITL9D (Acetaminophen)
RN  - 7S5I7G3JQL (Dexamethasone)
RN  - 8L70Q75FXE (Adenosine Triphosphate)
RN  - EC 1.1.1.27 (L-Lactate Dehydrogenase)
RN  - GAN16C9B8O (Glutathione)
RN  - R60L0SM5BC (Midazolam)
SB  - IM
MH  - Acetaminophen/metabolism
MH  - Adenosine Triphosphate/metabolism
MH  - Animals
MH  - Cell Survival/drug effects
MH  - Dexamethasone/pharmacology
MH  - Dose-Response Relationship, Drug
MH  - *Escherichia coli
MH  - Glutathione/metabolism
MH  - In Vitro Techniques
MH  - L-Lactate Dehydrogenase/metabolism
MH  - Lipopolysaccharides/*toxicity
MH  - Liver/cytology/*drug effects/metabolism
MH  - Midazolam/metabolism
MH  - Nitric Oxide/metabolism
MH  - Nitrites/metabolism
MH  - Proteins/metabolism
MH  - Rats
MH  - Rats, Wistar
EDAT- 2002/01/29 10:00
MHDA- 2002/03/28 10:01
CRDT- 2002/01/29 10:00
PHST- 2002/01/29 10:00 [pubmed]
PHST- 2002/03/28 10:01 [medline]
PHST- 2002/01/29 10:00 [entrez]
AID - S0887233301001047 [pii]
AID - 10.1016/s0887-2333(01)00104-7 [doi]
PST - ppublish
SO  - Toxicol In Vitro. 2002 Feb;16(1):47-54. doi: 10.1016/s0887-2333(01)00104-7.