TY - JOUR
T1 - Evidence that both cyclosporin and azathioprine prevent warm ischemia reperfusion injury to the rat liver
AU - Kawano, Katsunori
AU - Kim, Yang Il
AU - Ono, Masayuki
AU - Goto, Shigeru
AU - Kai, Tetsuji
AU - Kobayashi, Michio
PY - 1993/11
Y1 - 1993/11
N2 - The present work was undertaken to study whether the immunosuppressive agents cyclosporin (CyA) and azathioprine (AZA) ameliorate hepatic injury after warm ischemia. A temporary, normothermic liver ischemia was induced in female Sprague-Dawley rats. The rats were treated with CyA (10 mg/kg per day p.o.), AZA (8 mg/kg per day p.o.), or vehicles for 4 days before surgery. Seven-day survival rates after 60 min of ischemia improved significantly with CyA (76.2%, P<0.005) and AZA (78.6%, P<0.001) treatment, compared with 43.0% for the control group. The highest levels of serum aminotransferases in the treatment groups tended to be lower than those in the control group. The peak values for the percentage of liver necrosis, an indicator of the extent of hepatic necrosis, in the animals treated with CyA (26.1%±7.2%, mean±SEM) and AZA (32.1%±5.7%) were significantly lower than in the control group (47.4%±3.7%). Lipid peroxidative damage after reperfusion, assessed as the hepatic malondialdehyde (MDA) concentration, was significantly suppressed by pretreatment with CyA and AZA. Histological findings coincided with other parameters. This study demonstrates that both AZA and CyA have beneficial effects on normothermic liver ischemia in rats. It is suggested that the diminished lipid peroxidative damage with these agents might be one of the mechanisms responsible for this.
AB - The present work was undertaken to study whether the immunosuppressive agents cyclosporin (CyA) and azathioprine (AZA) ameliorate hepatic injury after warm ischemia. A temporary, normothermic liver ischemia was induced in female Sprague-Dawley rats. The rats were treated with CyA (10 mg/kg per day p.o.), AZA (8 mg/kg per day p.o.), or vehicles for 4 days before surgery. Seven-day survival rates after 60 min of ischemia improved significantly with CyA (76.2%, P<0.005) and AZA (78.6%, P<0.001) treatment, compared with 43.0% for the control group. The highest levels of serum aminotransferases in the treatment groups tended to be lower than those in the control group. The peak values for the percentage of liver necrosis, an indicator of the extent of hepatic necrosis, in the animals treated with CyA (26.1%±7.2%, mean±SEM) and AZA (32.1%±5.7%) were significantly lower than in the control group (47.4%±3.7%). Lipid peroxidative damage after reperfusion, assessed as the hepatic malondialdehyde (MDA) concentration, was significantly suppressed by pretreatment with CyA and AZA. Histological findings coincided with other parameters. This study demonstrates that both AZA and CyA have beneficial effects on normothermic liver ischemia in rats. It is suggested that the diminished lipid peroxidative damage with these agents might be one of the mechanisms responsible for this.
KW - Azathioprine, liver ischemia
KW - Cyclosporin, liver ischemia
KW - Ischemia, liver, rat
KW - Liver ischemia, rat
UR - http://www.scopus.com/inward/record.url?scp=0027484176&partnerID=8YFLogxK
U2 - 10.1007/BF00335970
DO - 10.1007/BF00335970
M3 - 文章
C2 - 8297462
AN - SCOPUS:0027484176
SN - 0934-0874
VL - 6
SP - 330
EP - 336
JO - Transplant International
JF - Transplant International
IS - 6
ER -