Journal
JOURNAL OF PARENTERAL AND ENTERAL NUTRITION
Volume 35, Issue 1, Pages 107-113Publisher
WILEY
DOI: 10.1177/0148607110374058
Keywords
inflammatory mediators; cytokines; resuscitation; cytochrome c; caspase-3; Bcl-2 protein; saffron; oxygen diffusion
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Funding
- Office of Naval Research [N00014-01-1-0151]
- American Heart Association [00000981]
- U.S. Department of Defense (Army Medical Research and Materials Command, USAMRIC) [W81XSH-06-1-530]
- National Institutes of Health [GM-50870]
- Coffey Foundation, Kansas City, Missouri
- Sosland Foundation, Kansas City, Missouri
- NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES [R01GM050870] Funding Source: NIH RePORTER
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Background: Hemorrhagic shock results in cellular damage and cell death. A primary mechanism is cellular apoptosis from mitochondrial damage. This study demonstrated that administration of crocetin to experimental animals during resuscitation from shock significantly improved postshock survival and reduced apoptosis. Crocetin is a component of saffron and has long been used in traditional medicine in Asia. Methods: Male Sprague-Dawley rats (350 +/- 30g) were randomly assigned to 1 of 4 groups of 8 animals. Hemorrhagic shock was induced by withdrawing blood until the mean arterial pressure was 35-40 mm Hg, and blood pressure was maintained at that level for 60 minutes with further withdrawals as needed. Resuscitation was carried out by administration of 21 mL/kg lactated Ringer's solution and return of shed blood, with or without concurrent administration of crocetin (2 mg/kg). Control animals were sham-treated with surgical preparation, without shock or resuscitation, and with and without crocetin. Rats were sacrificed 24 hours after completion of resuscitation. The extent of activation of hepatic apoptosis was established by measuring levels of hepatic cytosolic cytochrome c, caspase-3, and bcl-2. A separate group of 53 animals treated identically was used to assess survival. Results: Crocetin administration during resuscitation resulted in less extensive activation of hepatic apoptosis and significantly increased survival relative to controls. Conclusions: Crocetin administration to experimental animals during resuscitation post hemorrhage increased survival, at least in part by protecting the liver from activation of apoptotic cell death. This agent continues to show promise as a potential treatment strategy for hemorrhagic shock. (JPEN J Parenter Enteral Nutr. 2011;35:107-113)
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