Abstract
Aim-Background
To investigate the influence of N-acetyl-cysteine (NAC) and Atorvastatin, separately and combined, on the liver of rats after inducing ischaemia-reperfusion of the superior mesenteric artery.
Methods
Forty male rats aged 2½ months and weighing 220–250gr were randomly assigned to 5 groups of 8 rats. The rats in the first group were considered as controls. The second group was subjected to ischaemia of the superior mesenteric artery for 45 minutes, followed by reperfusion of the superior mesenteric artery for 3 hours, without any drug administration. In the third group, a single dose of Atorvastatin (10mg/kg) was administered 24 hours before the phase of ischaemia. The fourth group received a single dose of N-acetyl-cysteine (160mg/kg) 24 hours before the phase of ischaemia. The fifth group was given both drugs simultaneously 24 hours before the phase of ischaemia.
Three hours after reperfusion of the superior mesenteric artery, the liver was surgically removed and prepared for histological examination.
Results
The histological examination of liver tissue samples revealed diffuse necrosis of hepatocytes in the group without any drug administration prior to ischaemia-reperfusion. The groups of animals that were treated with NAC or Atorvastatin or the combination of both drugs showed quite a different histological picture with focal necrosis of hepatocytes and less degenerative lesions.
Conclusions
This study shows that pretreatment with NAC, Atorvastatin and their combination protects the liver from injury induced by intestinal ischaemia-reperfusion. This is ascribed to the antioxidant and anti-inflammatory effect of the above-mentioned drugs.
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References
Pierro A, Eaton S. Intestinal ischemia reperfusion injury and multisystem organ failure. Semin Pediatr Surg 2004;13:11–17.
Homer-Vanniasinkam S, Crinnion JN, Gough MJ. Postischaemic organ dysfunction: a review. Eur J Vasc Endovasc Surg 1997;14:195–203.
Radhakrishnan RS, Radhakrishnan GL, Radhakrishnan HR, et al. Pretreatment with bone morphogenetic protein-7 (BMP-7) mimics ischemia preconditioning following intestinal ischemia/reperfusion injury in the intestine and liver. Shock 2008;30:532–536.
Hassoun HT, Kone BC, Mercer DW, Moody FG, Weisbrodt NW, Moore FA. Post-injury multiple organ failure: the role of the gut. Shock 2001;15:1–10.
Moore-Olufemi SD, Kozar RA, Moore FA, et al. Ischemic preconditioning protects against gut dysfunction and mucosal injury after ischemia/reperfusion injury. Shock 2005;23:258–263.
Horie Y, Ishii H. Liver dysfunction elicited by gut ischemiareperfusion. Pathophysiology 2001;8:11–20.
Leister I, Mbachu EM, Post S, et al. Vasoactive intestinal polypeptide and gastrin-releasing peptide attenuate hepatic microvasculatory disturbances following intestinal ischemia and reperfusion. Digestion. 2002;66:186–192.
Yao YM, Sheng ZY, Yu Y, et al. The potential etiologic role of tumor necrosis factor in mediating multiple organ dysfunction in rats following intestinal ischemia-reperfusion injury. Resuscitation. 1995;29:157–168.
Turnage RH, Bagnasco J, Berger J, Guice KS, Oldham KT, Hinshaw DB. Hepatocellular Oxidant stress following intestinal ischemia reperfusion injury. Journal of surgical research 1999, 51:467–471.
Hameed Mallick I, Yang W, Winslet MC, Seifalian AM. Ischemia-reperfusion injury of the intestine and protective strategies against injury. Digestive Diseases and Sciences, September 2004, Vol. 49, No. 9 pp. 1359–1377
H Yasuhara. Acute Mesenteric Ischemia: The Challenge of Gastroenterology Department of Surgery, Teikyo University Ichihara Hospital, 3426-3 Anesaki, Ichihara, Chiba 299-0111, Japan Surg Today 2005 35:185–195
Y Abe, Hines IN, Zibari G, Pavlick K, Gray L, Kitagawa Y, Grisham MB. Mouse model of liver ischemia and reperfusion injury: method for studying reactive oxygen and nitrogen metabolites in vivo. Free Radical Biology & Medicine 2009 46:1–7.
Horie Y, Wolf R, Miyasaka M, Anderson DC, Granger DN. Leukocyte adhesion and hepatic microvascular responses to intestinal ischemia/reperfusion in rats. Gastroenterology. 1996;111:666–673.
Turnage RH, Guice KS, Oldham KT, Bagnasco J, Weatherbee L. Evidence for a neutrophil-related acute liver injury following intestinal ischemia-reperfusion. Circ Shock 1990; 31:42.
Turnage RH, Oldham KT, Guice KS, Hinshaw DB, Weatherbee L. Hepatic injury following intestinal ischemia-reperfusion. FASEB 4(3):1990, A761.
Smyrniotis V, Arkadopoulos N, Kostopanagiotou G, et al. Attenuation of ischemic injury by N-acetylcysteine preconditioning of the liver. J Surg Res. 2005 Nov;129(1):31–37.
Glantzounis GK, Salacinski HJ, Yang W, Davidson BR, Seifalian AM. The contemporary role of antioxidant therapy in attenuating liver ischemia-reperfusion injury: a review. Liver Transpl. 2005; 11(9):1031–1047.
Daniel Pella, Rafael Rybar and viola Mechirova. Pleiotropic effects of statins. Acta Cardiol Sin 2005;21:190–198
Hajipour B, Somi MH, Saberifar F, Hemmati MR, Asl NA, Moein A, Vatankhah AM, Nourazar AR, Nasirizade MR. Simvastatin attenuates intestinal ischemia/reperfusion induced injury in rat. Folia Morphol.Warz.2009Aug: Vol. 68, No. 3, pp. 156–162
Narwal R, Akhlaghi F, Åsberg A, Hermann M, Rosenbaum SE. Development of a Population Pharmacokinetic Model for Atorvastatin Acid and Its Lactone Metabolite. Clin Pharmacokinet 2010; 49(10):693–702
Mensah K, Mocanu MM, Yellon DM. Failure to protect the myocardium against ischemia/reperfusion injury after chronic atorvastatin treatment is recaptured by acute atorvastatin treatment: a potential role for phosphatase and tensin homolog deleted on chromosome ten? J Am Coll Cardiol 2005;45(8):1287–1291.
Kaplan N, Yagmurdur H, Kilinc K, Baltaci B, Tezel S. The protective effects of intravenous anesthetics and verapamil in gut ischemia/reperfusion-induced liver injury. Anesth Analg 2007;105:1371–1378.
Hai-Dong Zhao, Feng Zhang, Gang Shen, Yu-Bing Li, Ying-Hua Li. Sulforaphane protects liver injury induced by intestinal ischemia reperfusion through Nrf 2-ARE pathway World J Gastroenterology 2010; 16(24):3002–3010
Ji-Hong Yao, Xue-Song Zhang, Shu-Sen Zheng, Prophylaxis with carnosol attenuates liver injury induced by intestinal ischemia/reperfusion World J Gastroenterol. 2009;15(26):3240–3245.
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Alexandropoulos, D., Bazigos, G., Tragotsalou, N. et al. The separate and combined influence of antioxidant and anti-inflammatory drugs on the liver during ischaemia-reperfusion of the superior mesenteric artery: An experimental study. Hellenic J Surg 85, 254–260 (2013). https://doi.org/10.1007/s13126-013-0049-x
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DOI: https://doi.org/10.1007/s13126-013-0049-x