Effect of artificial cells on hepatic function after ischemia-reperfusion injury in liver.
BACKGROUND
The liver suffers from ischemia/reperfusion injury during transplantation. Reactive oxygen species generated by xanthine oxidase during reperfusion of the ischemic liver may be partially responsible for the hepatic injury. Oxygen free radicals are removed by antioxidant enzymes such as superoxide dismutase (SOD), catalase, and glutathione peroxidase. Using glutaraldehyde and lysine we constructed crosslinked hemoglobin, containing SOD and catalase, and assessed its ability to protect against ischemia/reperfusion injury during transplantation.


METHODS
In contrast to the sham-operated control groups, blood was exchanged using crosslinked hemoglobin (polyHb) a PolyHb-SOD-catalase (PSC) group. After ischemia/reperfusion injury, several parameters of hepatic damage and oxygen free radicals were measured as well as microscopic examination.


RESULTS
Alanine aminotransferase, aspartate aminotransferase, superoxide production, hydrogen peroxide, and malondialdehyde levels were higher among the PolyHb group than sham-operated controls. The PolyHb group revealed a few apoptotic bodies, some acute inflammatory infiltrates in the sinusoids, nuclear fragmentations, cell shrinkage, and chromatin clumping with formation of apoptotic bodies in the apoptotic cells under microscopic examination. Alanine aminotransferase, aspartate aminotransferase, superoxide production, and hydrogen peroxide levels were lower in the PSC than the PolyHb group. Hepatic structures were well preserved in the PSC group.


CONCLUSIONS
Reactive oxygen species contribute to hepatic dysfunction with morphologic changes. PSC is effective to reduce hepatic damage by lowering oxygen free radical-mediated injury after ischemia/reperfusion in the liver.
Chang
E J
EJ
Institute for Medical Science and Chronic Disease Research Center, Keimyung University School of Medicine, Daegu, Korea.
Lee
S H
SH
Mun
K C
KC
Suh
S I
SI
Bae
J H
JH
Kim
S P
SP
Choi
H J
HJ
Cho
K B
KB
Hwang
J S
JS
D000818:Animals; D001802:Blood Substitutes / Q000494:pharmacology; D002374:Catalase / Q000494:pharmacology*; D005609:Free Radicals / Q000378:metabolism; D006454:Hemoglobins / Q000494:pharmacology*; D007511:Ischemia; D008099:Liver / Q000502:physiology*; D008111:Liver Function Tests; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000503:physiopathology*; D013482:Superoxide Dismutase / Q000494:pharmacology*
D001802:Blood Substitutes; D005609:Free Radicals; D006454:Hemoglobins; C037158:polyhemoglobin; D002374:Catalase; D013482:Superoxide Dismutase; C086134:polyhemoglobin-superoxide dismutase-catalase