Oxidative DNA damage after transplantation of the liver and small intestine in pigs.
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-1 kg-1 and 2 1/2 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.
Loft
S
S
Department of Pharmacology, Surgery C, Medicine A, and Anaesthesia, Righospitalet, University of Copenhagen, Denmark.
Larsen
P N
PN
Rasmussen
A
A
Fischer-Nielsen
A
A
Bondesen
S
S
Kirkegaard
P
P
Rasmussen
L S
LS
Ejlersen
E
E
Tornøe
K
K
Bergholdt
R
R
D000080242:8-Hydroxy-2'-Deoxyguanosine; D000818:Animals; D004249:DNA Damage; D003849:Deoxyguanosine / Q000031:analogs & derivatives / Q000652:urine; D007421:Intestine, Small / Q000098:blood supply / Q000378:metabolism / Q000637:transplantation*; D008099:Liver / Q000098:blood supply / Q000378:metabolism; D016031:Liver Transplantation; D018384:Oxidative Stress; D015427:Reperfusion Injury / Q000378:metabolism*; D013552:Swine
D000080242:8-Hydroxy-2'-Deoxyguanosine; D003849:Deoxyguanosine