Treatment with beta-SQAG9 prevents rat hepatic ischemia-reperfusion injury.
BACKGROUND
Ischemia-reperfusion (I/R) injury occurs in various situations, including transplantation, trauma, and shock. We previously reported that the synthetic beta-SQDG (18:0), which was derived from sulfoquinovosyl diacylglycerol of the sea urchin, possessed immunosuppressive effects, such as inhibition of T-cell responses in human allogenic human mixed lymphocyte reactions (MLR) and skin allograft survival in rats. beta-SQAG9 was synthesized from beta-SQDG (18:0) to improve structural stability in aqueous solution with the same biological activities to bind to CD62L (L-selectin) and CD62P (P-selectin) in vitro. We hypothesized that beta-SQAG9 might attenuate leukocyte rolling on the endothelium and neutrophil infiltration in which L-selectin and P-selectin are key molecules. We investigated the protective effect of beta-SQAG9 against hepatic I/R injury.


METHODS
Male Lewis rats were divided into 6 groups: sham, control, and treatment. Rats in the control, and the treatment groups were subjected to hepatic ischemia for 30 minutes. They were injected with PBS or beta-SQAG9 at doses of 5, 10, 25, and 50 mg/kg into the penile vein immediately before reperfusion. To assess the damage to the hepatic parenchyma, aspartate aminotransferase (AST), alanine aminotransferase (ALT), and lactate dehydrogenase (LDH) were measured and histological evaluation was performed at 6 hours after reperfusion.


RESULTS
In the group treated with beta-SQAG9 at a dose of 10 mg/kg, AST, ALT, and LDH were significantly reduced, and the amount of neutrophil infiltration also was significantly reduced.


CONCLUSIONS
Our data suggest that SQAG-9 (10 mg/kg) reduces the warm hepatic I/R injury.
Shima
H
H
Department of Surgery, Sapporo Medical University School of Medicine, Sapporo, Japan.
Tsuruma
T
T
Sahara
H
H
Takenouchi
M
M
Takahashi
N
N
Iwayama
Y
Y
Yagihashi
A
A
Watanabe
N
N
Sato
N
N
Hirata
K
K
D000818:Animals; D006017:Glycolipids / Q000302:isolation & purification / Q000627:therapeutic use*; D007166:Immunosuppressive Agents / Q000302:isolation & purification / Q000627:therapeutic use; D008081:Liposomes; D008099:Liver / Q000187:drug effects / Q000473:pathology; D008102:Liver Circulation; D008297:Male; D009336:Necrosis; D009504:Neutrophils / Q000473:pathology; D051381:Rats; D011917:Rats, Inbred Lew; D015427:Reperfusion Injury / Q000517:prevention & control*; D012617:Sea Urchins
D006017:Glycolipids; D007166:Immunosuppressive Agents; D008081:Liposomes; C496611:sulfoquinovosylacylglycerol