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Crocetin Inhibits mRNA Expression for Tumor Necrosis Factor- , Interleukin-1β, and Inducible Nitric Oxide Synthase in Hemorrhagic Shock
Rongjie Yang, MD,
Xiaoyu Tan, MD,
Ann M. Thomas, BS,
Jing Shen, MD,
Nilofer Qureshi, PhD,
David C. Morrison, PhD and
Charles W. Van Way, III, MD
From the Department of Surgery, Shock/Trauma Research Center, University
of Missouri–Kansas City, Kansas City, Missouri
Correspondence: Charles W. Van Way III, MD, Department of Surgery,
Shock/Trauma Research Center, UMKC, 2301 Holmes Street, Kansas City, Missouri.
Electronic mail may be sent to charles.
vanway{at}tmcmed.org.
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- ), interleukin-1 (IL-1β) 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-, IL-1β, iNOS, and β-actin). Results: Liver
mRNA expression for TNF-, IL-1β, 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-, IL-1β, 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.
Journal of Parenteral and Enteral Nutrition, Vol. 30, No. 4,
297-301 (2006)
DOI: 10.1177/0148607106030004297
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