Protective effects of apocynin on "two-hit" injury induced by hemorrhagic shock and lipopolysaccharide.

AIM: 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.
CONCLUSION: Apocynin could preventively ameliorate "two-hit" injury in rats
induced by hemorrhagic shock and LPS insult.