PMID- 11595380
OWN - NLM
STAT- MEDLINE
DCOM- 20020110
LR  - 20190826
IS  - 0891-5849 (Print)
IS  - 0891-5849 (Linking)
VI  - 31
IP  - 8
DP  - 2001 Oct 15
TI  - Cold-induced apoptosis in isolated rat hepatocytes: protective role of 
      glutathione.
PG  - 954-61
AB  - Liver conservation for transplantation is usually made at 2-4 degrees C. We 
      studied the effect of rewarming to 37 degrees C for up to 3 h of rat hepatocytes 
      kept at 4 degrees C for 20 h, modulating intracellular glutathione (GSH) 
      concentration either with a GSH precursor (N-acetyl-L-cysteine, NAC), or with GSH 
      depleting agents (diethylmaleate and buthionine sulfoximine, DEM/BSO). Untreated 
      hepatocytes showed time-dependent production of reactive oxygen species (ROS), 
      lipid peroxidation, chromatin condensation and membrane blebbing, decrease in GSH 
      concentration, and protein sulfhydryl groups. Fluorochromatization with Propidium 
      Iodide (PI) and Annexin V (AnxV) of cells rewarmed for 1 h caused an increase of 
      AnxV-positive cells without PI staining and any observed lactate dehydrogenase 
      leakage. TUNEL and DNA-laddering tests were negative for all times and 
      treatments, indicating that apoptosis may occur without DNA fragmentation. Cold 
      preservation and rewarming in the presence of NAC induced a significant 
      improvement in the morphology, less oxidative stress and apoptosis. Conversely, 
      DEM/BSO caused a marked deterioration of morphology, increase of oxidative stress 
      and apoptosis. These results suggested that marked changes in GSH status might 
      play a critical role in triggering apoptosis during cold preservation of isolated 
      rat hepatocytes. NAC, added before rewarming, might represent a therapeutic 
      approach for preventing the early events of apoptosis during cold storage.
FAU - Vairetti, M
AU  - Vairetti M
AD  - Department of Internal Medicine and Therapeutics, University of Pavia, Pavia, 
      Italy. vairetti@botta.unipv.it
FAU - Griffini, P
AU  - Griffini P
FAU - Pietrocola, G
AU  - Pietrocola G
FAU - Richelmi, P
AU  - Richelmi P
FAU - Freitas, I
AU  - Freitas I
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Free Radic Biol Med
JT  - Free radical biology & medicine
JID - 8709159
RN  - 0 (Maleates)
RN  - 0 (Reactive Oxygen Species)
RN  - 5072-26-4 (Buthionine Sulfoximine)
RN  - G81WQB56OL (diethyl maleate)
RN  - GAN16C9B8O (Glutathione)
RN  - WYQ7N0BPYC (Acetylcysteine)
SB  - IM
MH  - Acetylcysteine/*metabolism/pharmacology
MH  - Animals
MH  - Apoptosis/*physiology
MH  - Buthionine Sulfoximine/metabolism/pharmacology
MH  - Cold Temperature
MH  - Glutathione/agonists/antagonists & inhibitors/*metabolism
MH  - Hepatocytes/*metabolism
MH  - Hypothermia/*metabolism
MH  - Lipid Peroxidation/physiology
MH  - Male
MH  - Maleates/metabolism/pharmacology
MH  - Rats
MH  - Rats, Wistar
MH  - Reactive Oxygen Species/metabolism
MH  - Rewarming
EDAT- 2001/10/12 10:00
MHDA- 2002/01/11 10:01
CRDT- 2001/10/12 10:00
PHST- 2001/10/12 10:00 [pubmed]
PHST- 2002/01/11 10:01 [medline]
PHST- 2001/10/12 10:00 [entrez]
AID - S0891584901006700 [pii]
AID - 10.1016/s0891-5849(01)00670-0 [doi]
PST - ppublish
SO  - Free Radic Biol Med. 2001 Oct 15;31(8):954-61. doi: 
      10.1016/s0891-5849(01)00670-0.