title: Crocetin inhibits mRNA expression for tumor necrosis factor-alpha, interleukin-1beta, and inducible nitric oxide synthase in hemorrhagic shock.
abstract: BACKGROUND
  Inflammatory factors play an important role in cellular damage after shock and resuscitation. Crocetin, a saffron-derived carotenoid, has been shown to improve postshock recovery of cellular adenosine triphosphate (ATP) and to increase overall survival in an experimental model of hemorrhagic shock. The hypothesis of the present study is that treatment with crocetin at the beginning of resuscitation suppresses subsequent expression of messenger ribonucleic acid (mRNA) for tumor necrosis factor (TNF-alpha), interleukin-1 (IL-1beta) and inducible nitric oxide synthase (iNOS).
  
  
  METHODS
  Male Sprague-Dawley rats (n = 45, 350 +/- 30 g) were randomly assigned to 5 groups of 9 animals each. After anesthesia with isoflurane, the femoral artery and vein were surgically cannulated. Hemorrhagic shock was induced by withdrawing blood through the arterial cannula until the mean arterial pressure (MAP) was 25-30 mm Hg and maintained at the level for 30 minutes with further withdrawals. Resuscitation was carried out by giving 21 mL/kg Ringer's lactate (LR) and returning the shed blood, with or without the initial administration of crocetin (2 mg/kg). Controls were normal (anesthesia only), sham (surgical preparation), and shock (preparation and shock). Rats were killed 30 minutes after completion of resuscitation. Liver samples were collected for reverse transcription-polymerase chain reaction (RT-PCR) analysis of mRNA (TNF-alpha, IL-1beta, iNOS, and beta-actin).
  
  
  RESULTS
  Liver mRNA expression for TNF-alpha, IL-1beta, and iNOS was found in more animals in the shock and shock-plus-resuscitation groups than in the sham control group. The group resuscitated from shock with crocetin had mRNA expression for TNF-alpha, IL-1beta, and iNOS in fewer animals than either of the other shock groups and was no different from the sham control group.
  
  
  CONCLUSIONS
  Crocetin modified the hepatic mRNA expression of cytokines and iNOS in a shock model. This agent continues to show promise as a potential treatment for hemorrhagic shock.
authors.affiliation: Department of Surgery, Shock/Trauma Research Center, University of Missouri-Kansas City, Kansas City, Missouri, USA.
authors.forename: Rongjie
authors.initials: R
authors.lastname: Yang
authors.forename: Xiaoyu
authors.initials: X
authors.lastname: Tan
authors.forename: Ann M
authors.initials: AM
authors.lastname: Thomas
authors.forename: Jing
authors.initials: J
authors.lastname: Shen
authors.forename: Nilofer
authors.initials: N
authors.lastname: Qureshi
authors.forename: David C
authors.initials: DC
authors.lastname: Morrison
authors.forename: Charles W
authors.initials: CW
authors.lastname: Van Way
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000627:therapeutic use*; D002338:Carotenoids / Q000627:therapeutic use*; D053583:Interleukin-1beta / Q000378:metabolism; D008099:Liver / Q000201:enzymology / Q000378:metabolism*; D008297:Male; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis* / Q000037:antagonists & inhibitors / Q000378:metabolism; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D012771:Shock, Hemorrhagic / Q000188:drug therapy*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D014801:Vitamin A / Q000031:analogs & derivatives
chemical_list: D000975:Antioxidants; D053583:Interleukin-1beta; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; C487773:trans-sodium crocetinate; D014801:Vitamin A; D002338:Carotenoids; D052247:Nitric Oxide Synthase Type II