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 ± 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.

Effects of ubiquinol with fluid resuscitation following haemorrhagic shock on rat lungs, diaphragm, heart and kidneys

“…Haemorrhagic shock and reperfusion injury have been associated with organ damage and apoptosis. Studies show that the administration of antioxidants is effective in reducing apoptosis following HS in animal models (Yang et al 2011). Other investigators have observed that production of H 2 O 2 coincided with antioxidant depletion in cells undergoing apoptosis (Takayanagi et al 1987).…”

Anticancer effects of crocetin in human esophageal squamous cell carcinoma KYSE-150 cells

“…Crocetin, the major component of saffron, is a low molecular weight carotenoid compound ( 14 ). Numerous studies have been performed to indicate the medicinal properties of crocetin, including antioxidative ( 15 ), antihypertensive ( 16 ), antithrombotic ( 17 ), anti-inflammatory ( 18 ), cardioprotective ( 19 ), hepatoprotective ( 20 ) and neuroprotective ( 21 ) effects. Crocetin also exhibits anticancer and antitumor properties.…”

Anticancer Effect and Molecular Targets of Saffron Carotenoids

“…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 [116].…”