title: Carvacrol alleviates ischemia reperfusion injury by regulating the PI3K-Akt pathway in rats.
abstract: BACKGROUND
  Liver ischemia reperfusion (I/R) injury is a common pathophysiological process in many clinical settings. Carvacrol, a food additive commonly used in essential oils, has displayed antimicrobials, antitumor and antidepressant-like activities. In the present study, we investigated the protective effects of carvacrol on I/R injury in the Wistar rat livers and an in vitro hypoxia/restoration (H/R) model.
  
  
  METHODS
  The hepatoportal vein, hepatic arterial and hepatic duct of Wistar rats were isolated and clamped for 30 min, followed by a 2 h reperfusion. Buffalo rat liver (BRL) cells were incubated under hypoxia for 4 h, followed normoxic conditions for 10 h to establish the H/R model in vitro. Liver injury was evaluated by measuring serum levels of alanine aminotransferase (ALT) and aspatate aminotransferase (AST), and hepatic levels of superoxide dismutase (SOD), catalase (CAT), glutathione (GSH) and malondiadehyde (MDA), and hepatic histology and TUNEL staining. MTT assay, flow cytometric analysis and Hoechst 33258 staining were used to evaluate the proliferation and apoptosis of BRL cells in vitro. Protein expression was examined by Western Blot analysis.
  
  
  RESULTS
  Carvacrol protected against I/R-induced liver damage, evidenced by significantly reducing the serum levels of ALT and AST, histological alterations and apoptosis of liver cells in I/R rats. Carvacrol exhibited anti-oxidative activity in the I/R rats, reflected by significantly reducing the activity of SOD and the content of MDA, and restoring the activity of CAT and the content of GSH, in I/R rats. In the in vitro assays, carvacrol restored the viability and inhibited the apoptosis of BRL cells, which were subjected to a mimic I/R injury induced by hypoxia. In the investigation on molecular mechanisms, carvacrol downregulated the expression of Bax and upregulated the expression of Bcl-2, thus inhibited the activation of caspase-3. Carvacrol was also shown to enhance the phosphorylation of Akt.
  
  
  CONCLUSIONS
  The results suggest that carvacrol could alleviate I/R-induced liver injury by its anti-oxidative and anti-apoptotic activities, and warrant a further investigation for using carvacrol to protect I/R injury in clinic.
authors.affiliation: Department of General Surgery, the Fifth Affiliated Hospital of Harbin Medical University, Daqing, Heilongjiang Province, China.
authors.forename: Lida
authors.initials: L
authors.lastname: Suo
authors.affiliation: Department of General Surgery, the Fifth Affiliated Hospital of Harbin Medical University, Daqing, Heilongjiang Province, China.
authors.forename: Kai
authors.initials: K
authors.lastname: Kang
authors.affiliation: Department of General Surgery, Daqing Oilfield General Hospital, Daqing, Heilongjiang Province, China.
authors.forename: Xun
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Pharmacology, Daqing Campus of Harbin Medical University, Daqing, Heilongjiang Province, China.
authors.forename: Yonggang
authors.initials: Y
authors.lastname: Cao
authors.affiliation: Department of General Surgery, the Fifth Affiliated Hospital of Harbin Medical University, Daqing, Heilongjiang Province, China.
authors.forename: Haifeng
authors.initials: H
authors.lastname: Zhao
authors.affiliation: The Hepatosplenic Surgery Center, Department of General Surgery, the First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang Province, China.
authors.forename: Xueying
authors.initials: X
authors.lastname: Sun
authors.affiliation: Department of General Surgery, the Fifth Affiliated Hospital of Harbin Medical University, Daqing, Heilongjiang Province, China.
authors.forename: Liquan
authors.initials: L
authors.lastname: Tong
authors.affiliation: Department of General Surgery, the Fifth Affiliated Hospital of Harbin Medical University, Daqing, Heilongjiang Province, China.
authors.forename: Feng
authors.initials: F
authors.lastname: Zhang
mesh_terms: D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects; D001219:Aspartate Aminotransferases / Q000097:blood; D015153:Blotting, Western; D053148:Caspase 3 / Q000378:metabolism; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D000081007:Cymenes; D022781:Hepatocytes / Q000187:drug effects / Q000473:pathology; D008297:Male; D039821:Monoterpenes / Q000494:pharmacology / Q000627:therapeutic use*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000097:blood / Q000188:drug therapy* / Q000201:enzymology; D015398:Signal Transduction / Q000187:drug effects; D051028:bcl-2-Associated X Protein / Q000378:metabolism
chemical_list: D000410:Alanine Transaminase; D000975:Antioxidants; D001219:Aspartate Aminotransferases; D053148:Caspase 3; D000081007:Cymenes; D039821:Monoterpenes; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D051028:bcl-2-Associated X Protein; C073316:carvacrol
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