Crocetin, a constituent of saffron, has been shown not only to prevent
reactive oxygen species-induced hepatotoxicity and genotoxicity but also to increase whole-body oxygen consumption and survival. The present study was to determine whether
crocetin has beneficial effects on cardiac injury caused by
hemorrhagic shock and
resuscitation in rats. Anesthetized rats were bled to reduce mean arterial pressure (MAP) to 35 +/- 5 mmHg for 60 min and then resuscitated with their withdrawn shed blood and isotonic
sodium chloride solution.
Crocetin was administered via the duodenum at 50 mg/kg 40 min after
bleeding. We investigated MAP, serum
creatine kinase activity, the activity of
nuclear factor-kappaB, iNOS, and total
superoxide dismutase (T-SOD), as well as levels of NO,
malondialdehyde,
TNF-alpha, and
IL-6 in the heart at 2 h postresuscitation. Compared with control group,
crocetin significantly increased MAP from 10 min after administration to the end of the protocol except the period between 75 and 90 min after initial
bleeding, whereas serum
creatine kinase activity was dramatically decreased at 2 h postresuscitation. Myocardial
nuclear factor-kappaB activity, iNOS activity, NO,
malondialdehyde,
TNF-alpha, and
IL-6 were significantly elevated, whereas T-SOD activity was suppressed in the control group if compared with those of
sham animals. These parameters tended to be normalized in rats administered
crocetin. These results suggest that
crocetin blocks inflammatory cascades by inhibiting
reactive oxygen species production and preserving T-SOD activity to ameliorate the cardiac injury caused by
hemorrhage/
resuscitation.