Effects of Dexmedetomidine on Hepatic Ischemia Reperfusion Injury in Rats with Cholestasis and Liver Fibrosis
International Journal of Anesthesia and Clinical Medicine
Volume 6, Issue 2, December 2018, Pages: 50-56
Received: Oct. 6, 2018;
Accepted: Oct. 23, 2018;
Published: Nov. 13, 2018
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Yi Zou, Department of Anesthesiology, Hunan Provincial People’s Hospital (The First Affiliated Hospital of Hunan Normal University), Changsha, China
Le Zhang, Department of Vasculocardiology, Hunan Provincial People’s Hospital (The First Affiliated Hospital of Hunan Normal University), Changsha, China
Lai Wei, Department of Anesthesiology, Hunan Provincial People’s Hospital (The First Affiliated Hospital of Hunan Normal University), Changsha, China
Hongjue Huang, Department of Anesthesiology, Hunan Provincial People’s Hospital (The First Affiliated Hospital of Hunan Normal University), Changsha, China
Wenyan Chen, Department of Anesthesiology, Hunan Provincial People’s Hospital (The First Affiliated Hospital of Hunan Normal University), Changsha, China
Qian Huang, Department of Anesthesiology, Hunan Provincial People’s Hospital (The First Affiliated Hospital of Hunan Normal University), Changsha, China
Gaoyin Kong, Department of Anesthesiology, Hunan Provincial People’s Hospital (The First Affiliated Hospital of Hunan Normal University), Changsha, China
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Back ground: Liver complicated with cholestasis and fibrosis is vulnerable to ischemia reperfusion injury (IRI). Objectives: To investigate the effects of dexmedetomidine on hepatic ischemia reperfusion injury in rats with cholestasis and liver fibrosis. Material and Methods: Model of rats with cholestasis and liver fibrosis is established by bile duct ligation (BDL) for 18 days. Thirty-two male modeled SD rats were randomized into four groups (n=8): Group S: rats underwent laparotomy but the hepatic pedicle was not occluded. Group IRI: the hepatic pedicle was occluded for 30min. Group D10: dexmedetomidine 10μg/kg was injected intraperitoneally before hepatic ischemia. Group D100: dexmedetomidine 100μg/kg was injected intraperitoneally before hepatic ischemia. Blood samples were obtained for analysis of total billirubin (TBIL), direct billirubin (DBIL), aspertate transaminase (AST), alanine transaminase (ALT), and tumor necrosis factor-α (TNF-α). Liver tissues were obtained for analysis of superoxide dismutase (SOD) and malondialdehyde (MDA), and were observed after hemotoxylin-eosin (HE) or Masson staining for histopathological assessment. Results: TBIL and DBIL values were not significantly different between four groups (P > 0.05). AST, MDA and TNF-α values in group IRI, D10 and D100 were significantly higher than in group S, while SOD value were lower (P < 0.05), AST, MDA and TNF-α values in group D10 and D100 were significantly lower than in group IRI, while SOD values were higher (P < 0.05). The degrees of bile duct proliferation and fibrosis in liver tissues in four groups were similar. In group IRI, there were severe inflammatory cells infiltration, hepatocellular swelling and even local necrosis in liver tissue, but injuries in group D10 and D100 was moderate. Conclusions: Dexmedetomidine may attenuate hepatic IRI in rats with cholestasis and liver fibrosis, possibly by up-regulation of SOD activity and down-regulation of TNF-α expression.
Dexmedetomidine, Liver, Ischemia Reperfusion Injury, Cholestasis, Fibrosis
To cite this article
Effects of Dexmedetomidine on Hepatic Ischemia Reperfusion Injury in Rats with Cholestasis and Liver Fibrosis, International Journal of Anesthesia and Clinical Medicine.
Vol. 6, No. 2,
2018, pp. 50-56.
Copyright © 2018 Authors retain the copyright of this article.
This article is an open access article distributed under the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/
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Akoad ME, Pomfret EA. Surgical resection and liver transplantation for hepatocellular carcinoma. Clin Liver Dis. 2015 May; 19 (2):381-399.
Hemming AW, Reed AI, Fujita S, et al. Surgical management of hilar cholangiocarcinoma. Ann Surg. 2005; 241:693-699.
Sakpal SV, Babel N, Chamberlain RS. Surgical management of hepatolithiasis. HPB (Oxford). 2009; 11 (3):194-202.
Man K, Fan S-T, Ng IOL, et al. Prospective evaluation of pringle maneuver in hepatectomy for liver tumors by a randomized study. Annals of Surgery. 1997; 226 (6):704-713.
Scatton O, Zalinski S, Jegou D, et al. Randomized clinical trial of ischaemic preconditioning in major liver resection with intermittent Pringle manoeuvre. Br J Surg. 2011; 98 (9):1236-1243.
Tsui WM, Lam PW, Lee WK, et al. Primary hepatolithiasis, recurrent pyogenic cholangitis, and oriental cholangiohepatitis: a tale of 3 countries. Adv Anat Pathol. 2011; 18 (4):318-328.
Elias-Miró M, Jiménez-Castro MB, Rodés J, et al. Current knowledge on oxidative stress in hepatic ischemia/reperfusion. Free Radic Res. 2013; 47 (8):555-568.
Abu-Amara M, Yang SY, Tapuria N, et al. Liver ischemia/reperfusion injury: processes in inflammatory networks--a review. Liver Transpl. 2010; 16 (9):1016-1032.
Yoshidome H, Miyazaki M, Shimizu H, et al. Obstructive jaundice impairs hepatic sinusoidal endothelial cell function and renders liver susceptible to hepatic ischemia/reperfusion. J Hepatol. 2000; 33 (1):59-67.
Sugiyama Y, Ishizaki Y, Imamura H, et al. Effects of intermittent Pringle's manoeuvre on cirrhotic compared with normal liver. Br J Surg. 2010; 97 (7):1062-1069.
Bajwa S, Kulshrestha A. Dexmedetomidine: an adjuvant making large inroads into clinical practice. Ann Med Health Sci Res. 2013; 3 (4):475-483.
Cai Y, Xu H, Yan J, et al. Molecular targets and mechanism of action of dexmedetomidine in treatment of ischemia/reperfusion injury. Mol Med Rep. 2014; 9 (5):1542-1550.
Tüfek A, Tokgöz O, Aliosmanoglu I, et al. The protective effects of dexmedetomidine on the liver and remote organs against hepatic ischemia reperfusion injury in rats. Int J Surg. 2013; 11 (1):96-100.
Wang ZX, Huang CY, Hua YP, et al. Dexmedetomidine reduces intestinal and hepatic injury after hepatectomy with inflow occlusion under general anaesthesia: a randomized controlled trial. Br J Anaesth, 2014, 112 (6):1055-1064.
Karavias DD, Tsamandas AC, Tepetes K, et al. BCL-2 and BAX expression and cell proliferation, after partial hepatectomy with and without ischemia, on cholestatic liver in rats: an experimental study. J Surg Res. 2003; 110 (2):399-408.
Kloek JJ, Marsman HA, van Vliet AK, et al. Biliary drainage attenuates postischemic reperfusion injury in the cholestatic rat liver. Surgery. 2008; 144 (1):22-31.
Dan RG, Creţu OM, Mazilu O, et al. Postoperative morbidity and mortality after liver resection. Retrospective study on 133 patients. Chirurgia (Bucur). 2012; 107 (6):737-741.
Theodoraki K, Tympa A, Karmaniolou I, et al. Ischemia/reperfusion injury in liver resection: a review of preconditioning methods. Surg Today. 2011 May; 41 (5):620-629.
Dalle-Donne I, Rossi R, Colombo R, et al. Biomarkers of oxidative damage in human disease. Clin Chem. 2006; 52 (4):601-623.
Sahin T, Begeç Z, Toprak Hİ, et al. The effects of dexmedetomidine on liver ischemia-reperfusion injury in rats. J Surg Res. 2013 Jul; 183 (1):385-390.
Guellaen G, Aggerbeck M, Schmelck P, et al. Physiological and physiopathological modulations of the balance between alpha- and beta-adrenoreceptors. J Cardiovasc Pharmacol. 1982; 4 Suppl 1:S46-50.
Okajima F, Ui M. Predominance of beta-adrenergic over alpha-adrenergic receptor functions involved in phosphorylase activation in liver cells of cholestatic rats. Arch Biochem Biophys. 1984; 230 (2):640-651.
Pratap A, Panakanti R, Yang N, et al. Cyclopamine attenuates acute warm ischemia reperfusion injury in cholestatic rat liver: hope for marginal livers. Mol Pharm. 2011 Jun 6; 8 (3):958-968.