Protective effects of apocynin on "two-hit" injury induced by hemorrhagic shock and lipopolysaccharide.
OBJECTIVE
To evaluate the protective effects of apocynin on "two-hit" injury in rats.


METHODS
"Two-hit" injury model of rat was induced by hemorrhagic shock (40 mmHg for 45 min) followed by iv administration of lipopolysaccharide (LPS, 150 microg/kg). Rats were randomized into seven groups: Sham, LPS, hemorrhage, hemorrhage/LPS, and hemorrhage/LPS+apocynin (2.5, 5.0, and 10.0 mg/kg). Apocynin was dissolved in the resuscitation fluid (normal saline, NS) and administered iv for 2 h. After LPS or NS administration, the survival rates at 8 h, 16 h, 24 h, and 48 h were monitored. The content of malondialdehyde (MDA) was measured in lung at 3 h and 6 h after iv LPS and in serum before hemorrhage, after hemorrhage, and at 0, 0.5, 1, 2, 4, and 6 h after iv LPS. Myeloperoxidase (MPO) activity in lung and liver was examined at 3 h and 6 h after iv LPS/NS.


RESULTS
After "two-hit" injury, the survival rates of rats at 8 h, 16 h, 24 h, and 48 h were 64.3 %, 35.7 %, 28.6 %, and 14.3 % respectively, there were significant differences as compared to sham group (P<0.05 or P<0.01, respectively), the MDA level in lung and serum were significantly enhanced (P<0.01) as compared to sham group, and MPO activity in lung and liver after "two-hit" injury was also significantly increased (P<0.01). Apocynin treatment enhanced the mean arterial pressure (MAP) of hemorrhagic shock rats dose-dependently (P<0.05), increased the survival rate of "two-hit" injury rats, decreased the serum and lung MDA content, and downregulated MPO activity in lung and liver.


CONCLUSIONS
Apocynin could preventively ameliorate "two-hit" injury in rats induced by hemorrhagic shock and LPS insult.
Zhou
Rong
R
The Second Department of Research Institute of Surgery, Third Military Medical University, Chongqing 400042, China. zhourongtan@hotmail.com
Hu
De-Yao
DY
Liu
Liang-Ming
LM
Zhou
Xue-Wu
XW
D000098:Acetophenones / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology / Q000627:therapeutic use*; D005260:Female; D008070:Lipopolysaccharides / Q000633:toxicity*; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D009195:Peroxidase / Q000378:metabolism; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D012771:Shock, Hemorrhagic / Q000150:complications*; D018746:Systemic Inflammatory Response Syndrome / Q000139:chemically induced / Q000378:metabolism / Q000517:prevention & control*
D000098:Acetophenones; D000894:Anti-Inflammatory Agents, Non-Steroidal; D008070:Lipopolysaccharides; D008315:Malondialdehyde; C056165:acetovanillone; D009195:Peroxidase