Although
astringinin administration under adverse circulatory conditions is known to be protective, the mechanism by which
astringinin produces the salutary effects remains unknown. We hypothesize that
astringinin administration in males following
trauma-
hemorrhage decreases
cytokine production and protects against hepatic injury. Male Sprague-Dawley rats underwent
trauma-
hemorrhage (mean blood pressure: 40 mmHg for 90 min, then
resuscitation). Different doses of
astringinin (0.01, 0.03, 0.1, 0.3 mg/kg of
body weight) or vehicle were administered intravenously during
resuscitation. Concentrations of plasma
aspartate aminotransferase (AST) with
alanine aminotransferase (ALT) and various hepatic parameters were measured (n = 8 rats/group) at 24 h after
resuscitation. One-way ANOVA and Tukey testing were used for statistical analysis.
Trauma-
hemorrhage significantly increased plasma AST and ALT levels at 24 h postresuscitation; there was a dose-related benefit when
astringinin was administered at doses of 0.01 to 0.3 mg/kg. In
astringinin-treated (0.3 mg/kg) rats subjected to
trauma-
hemorrhage, there were significant improvements in liver
myeloperoxidase (MPO) activity (237.80 +/- 45.89 vs. 495.95 +/- 70.64 U/mg
protein, P < 0.05),
interleukin-6 (IL-6) levels (218.54 +/- 34.52 vs. 478.60 +/- 76.21 pg/mg
protein, P < 0.05),
cytokine-induced neutrophil
chemoattractant (CINC)-1 (88.32 +/- 20.33 vs. 200.70 +/- 32.68 pg/mg
protein, P < 0.05), CINC-3 (110.83 +/- 26.63 vs. 290.14 +/- 76.82 pg/mg
protein, P < 0.05) and
intercellular adhesion molecule (ICAM)-1 concentrations (1,868.5 +/- 211.5 vs. 3,645.0 +/- 709.2 pg/mg
protein, P < 0.05), as well as in histology. Results show that
astringinin significantly attenuates proinflammatory responses and hepatic injury after
trauma-
hemorrhage. In conclusion, the salutary effects of
astringinin administration on attenuation of hepatic injury following
trauma-
hemorrhage are likely due to reduction of pro-inflammatory mediator levels.