OXIDATIVE DNA DAMAGE AFTER TRANSPLANTATION OF THE LIVER AND SMALL INTESTINE IN PIGS
作者:
Steffen Loft,
Peter Larsen,
Allan Rasmussen,
Anne Fischer-Nielsen,
Stig Bondesen,
Preben Kirkegaard,
Lars Rasmussen,
Ellen Ejlersen,
Karen Tornøe,
Regine Bergholdt,
Henrik Poulsen,
期刊:
Transplantation
(OVID Available online 1995)
卷期:
Volume 59,
issue 1
页码: 16-20
ISSN:0041-1337
年代: 1995
出版商: OVID
数据来源: OVID
摘要:
Oxidative damage is thought to play an important role in ischemia/reperfusion injury, including the outcome of transplantation of the liver and intestine. We have investigated oxidative DNA damage after combined transplantation of the liver and small intestine in 5 pigs. DNA damage was estimated from the urinary excretion of the repair product 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG). In the first 1–3 hr after reperfusion of the grafts, 8-oxodG excretion was increased 2.9-fold (1.7–4.1; 95% confidence intervals;P<0.05). A control experiment included sham surgery with clamping of the suprarenal inferior caval vein in 2 pigs during steady state infusion of 8-oxodG. While the caval vein was clamped, the urinary excretion of 8-oxodG was almost blocked, whereas after removal of the clamp, the excretion returned to and did not exceed the preclamp levels. In a separate experiment with 2 pigs, the elimination of injected 8-oxodG was shown to adhere to first-order kinetics with a clearance and a terminal elimination half-life of approximately 4 ml min-1kg-1and 2½ hr, respectively. The injected dose was completely excreted into the urine within 4 hr. It is concluded that substantial oxidative damage to DNA results from reperfusion of transplanted small intestine and liver in pigs, as estimated from the readily excreted repair product 8-oxodG.
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