title: Ambroxol alleviates hepatic ischemia reperfusion injury by antioxidant and antiapoptotic pathways.
abstract: BACKGROUND
  Hepatic ischemia/reperfusion (HI/R) injury is a common pathologic process caused by many clinical settings, such as liver resection, liver transplantation, hypovolemic shock, and trauma. The use of ambroxol, which acts as a mucolytic agent, provides antioxidant and anti-inflammatory effects.
  
  
  METHODS
  A rat model of HI/R was induced by clamping the hepatic artery, the hepatoportal vein, and the bile duct with a vascular clamp for 30 minutes followed by reperfusion for 6 hours under anesthesia. The sham group underwent laparotomy without hepatic ischemia. The ambroxol group was injected into the tail vein in the ambroxol group 5 minutes before HI/R at one dose of 20 mg/kg, 80 mg/kg, or 140 mg/kg. The control group underwent the same procedure as the ambroxol group but with administration of physiological saline. Liver injury was evaluated by biochemical and histopathological examinations. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were assayed in serum samples. Superoxide dismutase (SOD), catalase (CAT), malondiadehyde (MDA), and glutathione (GSH) were spectrophotometrically measured. Furthermore, caspase-3, Bcl-2 and Bax expression as well as the level of c-Jun N-terminal kinases (JNK) we estimated activation.
  
  
  RESULTS
  Wistar rats that received 20, 80 mg or 140 mg of ambroxol displayed reduced HI/R injury compared with controls. Use of ambroxol reduced the histologic injury and significantly decreased serum ALT and AST levels. In addition, ambroxol enhanced the activity of hepatic tissue SOD and CAT, increasing GSH but decreasing MDA tissue contents. In the ambroxol group, Bcl-2 expression was increased and Bax and caspase-3 decreased compared with the controls. Furthermore, ambroxol reduced levels of phosphorylated JNK (P < .05).
  
  
  CONCLUSIONS
  These results indicated that ambroxol attenuated rat HI/R through upregulation of intracellular antioxidant and anti-apoptotic signaling pathways.
authors: Department of General Surgery, the Fifth Affiliated Hospital of Harbin Medical University, Daqing, Heilongjiang Province, China.
authors: K
authors: K
authors: Jiang
authors: X
authors: X
authors: Wang
authors: X
authors: X
authors: Mao
authors: H
authors: H
authors: Lao
authors: J
authors: J
authors: Zhang
authors: G
authors: G
authors: Wang
authors: Y
authors: Y
authors: Cao
authors: I
authors: I
authors: Tong
authors: F
authors: F
authors: Zhang
mesh_terms: D000551:Ambroxol / Q000494:pharmacology*; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D015415:Biomarkers / Q000097:blood; D053148:Caspase 3 / Q000378:metabolism; D004195:Disease Models, Animal; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D008099:Liver / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008107:Liver Diseases / Q000097:blood / Q000473:pathology / Q000517:prevention & control*; D008297:Male; D018384:Oxidative Stress / Q000187:drug effects*; D010766:Phosphorylation; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000097:blood / Q000473:pathology / Q000517:prevention & control*; D015398:Signal Transduction / Q000187:drug effects; D051028:bcl-2-Associated X Protein / Q000378:metabolism
chemical_list: D000975:Antioxidants; C494828:Bax protein, rat; D015415:Biomarkers; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; D000551:Ambroxol; D048031:JNK Mitogen-Activated Protein Kinases; C505410:Casp3 protein, rat; D053148:Caspase 3