title: Plant polyphenols attenuate hepatic injury after hemorrhage/resuscitation by inhibition of apoptosis, oxidative stress, and inflammation via NF-kappaB in rats.
abstract: OBJECTIVE
  Oxidative stress and inflammation contribute to hepatic injury after hemorrhage/resuscitation (H/R). Natural plant polyphenols, i.e., green tea extract (GTE) possess high anti-oxidant and anti-inflammatory activities in various models of acute inflammation. However, possible protective effects and feasible mechanisms by which plant polyphenols modulate pro-inflammatory, apoptotic, and oxidant signaling after H/R in the liver remain unknown. Therefore, we investigated the effects of GTE and its impact on the activation of NF-kappaB in the pathogenesis of hepatic injury induced by H/R.
  
  
  METHODS
  Twenty-four female LEWIS rats (180-250 g) were fed a standard chow (ctrl) or a diet containing 0.1% polyphenolic extracts (GTE) from Camellia sinensis starting 5 days before H/R. Rats were hemorrhaged to a mean arterial pressure of 30 ± 2 mmHg for 60 min and resuscitated (H/R and GTE H/R groups). Control groups (sham, ctrl, and GTE) underwent surgical procedures without H/R. Two hours after resuscitation, tissues were harvested.
  
  
  RESULTS
  Plasma alanine aminotransferase (ALT) and lactate dehydrogenase (LDH) increased 3.5-fold and fourfold, respectively, in vehicle-treated rats as compared to GTE-fed rats. Histopathological analysis revealed significantly decreased hepatic necrosis and apoptosis in GTE-fed rats after H/R. Real-time PCR showed that GTE diminished gene expression of pro-apoptotic caspase-8 and Bax, while anti-apoptotic Bcl-2 was increased after H/R. Hepatic oxidative (4-hydroxynonenal) and nitrosative (3-nitrotyrosine) stress as well as systemic IL-6 level and hepatic IL-6 mRNA were markedly reduced in GTE-fed rats compared with controls after H/R. Plant polyphenols also decreased the activation of both JNK and NFκB.
  
  
  CONCLUSIONS
  Taken together, GTE application blunts hepatic damage, apoptotic, oxidative, and pro-inflammatory changes after H/R. These results underline the important roles of JNK and NF-kappaB in inflammatory processes after H/R and the beneficial impact of plant polyphenols in preventing their activation.
authors.affiliation: Department of Trauma, Hand and Reconstructive Surgery, Hospitals of the Goethe-University Frankfurt am Main, 60590, Frankfurt, Germany. info@bornarelja.com
authors.forename: Borna
authors.initials: B
authors.lastname: Relja
authors.forename: Eva
authors.initials: E
authors.lastname: Töttel
authors.forename: Lara
authors.initials: L
authors.lastname: Breig
authors.forename: Dirk
authors.initials: D
authors.lastname: Henrich
authors.forename: Heinz
authors.initials: H
authors.lastname: Schneider
authors.forename: Ingo
authors.initials: I
authors.lastname: Marzi
authors.forename: Mark
authors.initials: M
authors.lastname: Lehnert
mesh_terms: D000208:Acute Disease; D000410:Alanine Transaminase / Q000097:blood; D000447:Aldehydes / Q000302:isolation & purification; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D000975:Antioxidants / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D053181:Caspase 8 / Q000235:genetics / Q000378:metabolism; D005260:Female; D005786:Gene Expression Regulation; D006470:Hemorrhage / Q000473:pathology; D007249:Inflammation / Q000473:pathology; D015850:Interleukin-6 / Q000097:blood; D007770:L-Lactate Dehydrogenase / Q000097:blood; D008099:Liver / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D016328:NF-kappa B / Q000378:metabolism*; D018384:Oxidative Stress / Q000187:drug effects*; D010936:Plant Extracts / Q000494:pharmacology*; D059808:Polyphenols / Q000494:pharmacology*; D012313:RNA / Q000302:isolation & purification; D051381:Rats; D011917:Rats, Inbred Lew; D012151:Resuscitation; D013662:Tea / Q000737:chemistry; D014443:Tyrosine / Q000031:analogs & derivatives / Q000302:isolation & purification; D051028:bcl-2-Associated X Protein / Q000235:genetics / Q000378:metabolism
chemical_list: D000447:Aldehydes; D000893:Anti-Inflammatory Agents; D000975:Antioxidants; C494828:Bax protein, rat; D015850:Interleukin-6; D016328:NF-kappa B; D010936:Plant Extracts; D059808:Polyphenols; D013662:Tea; D051028:bcl-2-Associated X Protein; C002744:3-nitrotyrosine; D014443:Tyrosine; D012313:RNA; D007770:L-Lactate Dehydrogenase; D000410:Alanine Transaminase; C505528:Casp8 protein, rat; D053181:Caspase 8; C027576:4-hydroxy-2-nonenal