TNF-alpha and heat-shock protein gene expression in ischemic-injured liver from fasted and non-fasted rats. Role of donor fasting in the prevention of reperfusion injury following liver transplantation.
We have previously shown that livers from long-term-fasted rats acquire tolerance to warm ischemic injury following transplantation, despite the fact that fasting depletes glycogen and ATP from the liver. The precise mechanism of the protective effect induced by donor fasting, however, is still a matter of controversy. In this experiment we determined heat-shock protein (GRP78) mRNA expression in livers during long-term fasting and TNF-alpha mRNA expression in transplanted livers exposed to warm ischemia. We also measured the concentration of TNF-alpha by ELISA in the ascitic fluid of fed and fasted rats injected intraperitoneally with zymosan to investigate why livers from fasted rats tolerate ischemic injury better. There seemed to be a positive correlation between GRP78 mRNA expression and survival. TNF-alpha secretion into the ascitic fluid of fasted rats was markedly suppressed, and fasting donor animals induced cytoprotective substances, such as GRP78, in the liver. These factors may contribute to the tolerance to ischemic injury produced by donor fasting.
Second Department of Surgery, School of Medicine, Hiroshima University, Japan.
M
M
Nishihara
R
R
Sumimoto
Y
Y
Fukuda
J H
JH
Southard
T
T
Asahara
H
H
Kawaishi
K
K
Dohi
D000818:Animals; D002352:Carrier Proteins / Q000235:genetics*; D000091342:Endoplasmic Reticulum Chaperone BiP; D005215:Fasting; D015870:Gene Expression; D006360:Heat-Shock Proteins / Q000235:genetics*; D016031:Liver Transplantation; D008297:Male; D018832:Molecular Chaperones / Q000235:genetics*; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D011914:Rats, Inbred BN; D015427:Reperfusion Injury / Q000517:prevention & control*; D014019:Tissue Donors; D014022:Tissue Survival; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics*
D002352:Carrier Proteins; D000091342:Endoplasmic Reticulum Chaperone BiP; D006360:Heat-Shock Proteins; D018832:Molecular Chaperones; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha