Polyethylene glycol-superoxide dismutase inhibits lipid peroxidation in hepatic ischemia/reperfusion injury.
BACKGROUND
Hepatic injury after ischemia/reperfusion is attributed to the development of oxygen free radical (OFR)-mediated lipid peroxidation--a process that can be measured through its byproducts, specifically malondialdehyde. The use of free radical scavengers can offer significant protection against OFR-induced liver injury. We hypothesize that a new potent OFR scavenger, polyethylene glycol-superoxide dismutase (PEG-SOD), can inhibit OFR-mediated lipid peroxidation in hepatic ischemia/reperfusion injury.


METHODS
Twelve male Sprague-Dawley rats (300-350 g) were subjected to occlusion of the left and middle hepatic arteries and portal veins for 90 min, followed by 120 min reperfusion. PEG-SOD (5000 units/kg) was given intravenously before vascular occlusion and again immediately upon reperfusion to six rats. Normal saline was given to the remaining six rats to be used as a control group. The right hepatic lobe (used as internal control) and left hepatic lobe were harvested separately and tissue malondialdehyde was measured.


RESULTS
A marked increase in lipid peroxide was found in the normal saline group after 2 h reperfusion. Treatment with PEG-SOD prevented the rise in tissue malondialdehyde. The mean difference in the malondialdehyde between the left and right hepatic lobes were 13.20 +/- 6.35 and 1.70 +/- 3.65 nmol/g in the normal saline (control) and PEG-SOD groups, respectively. This difference was found to be statistically significant (P < 0.005) using Student's t-test.


CONCLUSIONS
PEG-SOD can effectively attenuate hepatic ischemia/reperfusion injury by inhibiting OFR-mediated lipid peroxidation.
Nguyen
W D
WD
Department of Surgery, Washington Hospital Center, Washington, District of Columbia 20010, USA.
Kim
D H
DH
Alam
H B
HB
Provido
H S
HS
Kirkpatrick
J R
JR
D000818:Animals; D015415:Biomarkers; D016166:Free Radical Scavengers / Q000494:pharmacology / Q000627:therapeutic use*; D015227:Lipid Peroxidation / Q000187:drug effects*; D008099:Liver / Q000293:injuries* / Q000378:metabolism; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D011092:Polyethylene Glycols / Q000494:pharmacology / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000378:metabolism / Q000517:prevention & control*; D013482:Superoxide Dismutase / Q000494:pharmacology / Q000627:therapeutic use*
D015415:Biomarkers; D016166:Free Radical Scavengers; D011092:Polyethylene Glycols; D008315:Malondialdehyde; D013482:Superoxide Dismutase; C063471:polyethylene glycol-superoxide dismutase