title: Crocetin reduces activation of hepatic apoptotic pathways and improves survival in experimental hemorrhagic shock.
abstract: 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 ± 30 g) 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.
authors.affiliation: Thoracic Surgery, Liaoning Province Cancer Hospital.
authors.forename: Rongjie
authors.initials: R
authors.lastname: Yang
authors.forename: Kathy
authors.initials: K
authors.lastname: Vernon
authors.forename: Ann
authors.initials: A
authors.lastname: Thomas
authors.forename: David
authors.initials: D
authors.lastname: Morrison
authors.forename: Nilofer
authors.initials: N
authors.lastname: Qureshi
authors.forename: Charles W
authors.initials: CW
authors.lastname: Van Way
mesh_terms: D000818:Animals; D017209:Apoptosis; D002338:Carotenoids / Q000494:pharmacology*; D053148:Caspase 3 / Q000032:analysis; D027622:Crocus / Q000737:chemistry*; D045304:Cytochromes c / Q000032:analysis; D004195:Disease Models, Animal; D008099:Liver / Q000473:pathology; D008297:Male; D008517:Phytotherapy; D010936:Plant Extracts / Q000494:pharmacology*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000032:analysis; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D012151:Resuscitation; D012771:Shock, Hemorrhagic / Q000188:drug therapy*; D014801:Vitamin A / Q000031:analogs & derivatives
chemical_list: D010936:Plant Extracts; D019253:Proto-Oncogene Proteins c-bcl-2; C487773:trans-sodium crocetinate; D014801:Vitamin A; D002338:Carotenoids; D045304:Cytochromes c; C505410:Casp3 protein, rat; D053148:Caspase 3