Polyphenols of Camellia sinenesis decrease mortality, hepatic injury and generation of cytokines and reactive oxygen and nitrogen species after hemorrhage/resuscitation in rats

BMC Complement Altern Med. 2010 Aug 24:10:46. doi: 10.1186/1472-6882-10-46.

Abstract

Background: Reactive oxygen species (ROS) and reactive nitrogen species (RNS) are produced during hemorrhagic shock and resuscitation (H/R), which may contribute to multiple organ failure. The Aim of this study was to test the hypothesis that green tea (Camellia sinenesis) extract containing 85% polyphenols decreases injury after H/R in rats by scavenging ROS and RNS.

Methods: Female Sprague Dawley rats were given 100 mg polyphenol extract/kg body weight or vehicle 2 h prior to hemorrhagic shock. H/R was induced by two protocols: 1) withdrawal of blood to a mean arterial pressure of 40 mm Hg followed by further withdrawals to decrease blood pressure progressively to 28 mm Hg over 1 h (severe), and 2) withdrawal of blood to a sustained hypotension of 40 mm Hg for 1 h (moderate). Rats were then resuscitated over 1 h with 60% of the shed blood volume plus twice the shed blood volume of lactated Ringer's solution. Serum samples were collected at 10 min and 2 h after resuscitation. At 2 or 18 h, livers were harvested for cytokine and 3-nitrotyrosine quantification, immunohistochemical detection of 4-hydroxynonenol (4-HNE) and inducible nitric oxide synthase (iNOS) protein expression.

Results: After severe H/R, 18-h survival increased from 20% after vehicle to 70% after polyphenols (p < 0.05). After moderate H/R, survival was greater (80%) and not different between vehicle and polyphenols. In moderate H/R, serum alanine aminotransferase (ALT) increased at 10 min and 2 h postresuscitation to 345 and 545 IU/L, respectively. Polyphenol treatment blunted this increase to 153 and 252 IU/L at 10 min and 2 h (p < 0.01). Polyphenols also blunted increases in liver homogenates of TNFalpha (7.0 pg/mg with vehicle vs. 4.9 pg/mg with polyphenols, p < 0.05), IL-1beta (0.80 vs. 0.37 pg/mg, p < 0.05), IL-6 (6.9 vs. 5.1 pg/mg, p < 0.05) and nitrotyrosine (1.9 pg/mg vs. 0.6 pg/mg, p < 0.05) measured 18 h after H/R. Hepatic 4-HNE immunostaining indicative of lipid peroxidation also decreased from 4.8% after vehicle to 1.5% after polyphenols (p < 0.05). By contrast, polyphenols did not block increased iNOS expression at 2 h after H/R.

Conclusion: Polyphenols decrease ROS/RNS formation and are beneficial after hemorrhagic shock and resuscitation.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Alanine Transaminase / blood
  • Animals
  • Blood Transfusion
  • Camellia sinensis / chemistry*
  • Cytokines / metabolism
  • Female
  • Flavonoids / pharmacology
  • Flavonoids / therapeutic use*
  • Lipid Peroxidation / drug effects
  • Liver / drug effects
  • Liver / metabolism
  • Liver Diseases / metabolism
  • Liver Diseases / prevention & control*
  • Nitric Oxide Synthase Type II / metabolism
  • Phenols / pharmacology
  • Phenols / therapeutic use*
  • Phytotherapy
  • Plant Extracts / pharmacology
  • Plant Extracts / therapeutic use*
  • Polyphenols
  • Rats
  • Rats, Sprague-Dawley
  • Reactive Nitrogen Species / metabolism*
  • Reactive Oxygen Species / metabolism*
  • Resuscitation
  • Shock, Hemorrhagic / blood
  • Shock, Hemorrhagic / drug therapy*
  • Shock, Hemorrhagic / mortality
  • Tyrosine / analogs & derivatives
  • Tyrosine / metabolism

Substances

  • Cytokines
  • Flavonoids
  • Phenols
  • Plant Extracts
  • Polyphenols
  • Reactive Nitrogen Species
  • Reactive Oxygen Species
  • 3-nitrotyrosine
  • Tyrosine
  • Nitric Oxide Synthase Type II
  • Alanine Transaminase