Oxidative stress mediates cell injury during ischaemia/reperfusion. On the other hand, experimental findings suggest that ROS (reactive oxygen species) induce processes leading to ischaemic preconditioning. The extent and source of oxidative stress and its effect on antioxidant status in the human liver during intermittent ischaemia and reperfusion remains ill-defined. Therefore the aim of the present study was to investigate the occurrence of oxidative stress in humans undergoing liver resection. Liver biopsies, and arterial and hepatic venous blood samples were taken from ten patients undergoing hepatectomy with an intermittent Pringle manoeuvre. Plasma MDA (malondialdehyde) and hepatic GSSG levels were measured as markers of oxidative stress and plasma uric acid as a marker of xanthine oxidase activity. In addition, changes in hepatosplanchnic consumption of plasma antioxidants and hepatic levels of carotenoids and glutathione (GSH) were measured. After ischaemia, hepatosplanchnic release of MDA and increased hepatic GSSG levels were found. This was accompanied by the release of uric acid, reflecting xanthine oxidase activity. During reperfusion, ongoing oxidative stress was observed by further increases in hepatic GSSG content and hepatosplanchnic MDA release. Uric acid release was minimal during reperfusion. A gradual decrease in plasma antioxidant capacity and net hepatosplanchnic antioxidant uptake was observed upon prolonged cumulative ischaemia. Oxidative stress occurs during hepatic ischaemia in man mainly due to xanthine oxidase activity. Interestingly, the gradual decline in plasma antioxidant capacity and net hepatosplanchnic antioxidant uptake during prolonged cumulative ischaemia, preserved both hydrophilic and lipophilic hepatic antioxidant levels. Decreasing plasma levels and net hepatosplanchnic uptake of plasma antioxidants may warrant antioxidant supplementation, although it should be clarified to what extent limitation of oxidative stress compromises ROS-dependent pathways of ischaemic preconditioning.
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April 2008
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Research Article|
March 13 2008
Decreased hepatosplanchnic antioxidant uptake during hepatic ischaemia/reperfusion in patients undergoing liver resection
Marcel C. G. van de POLL;
Marcel C. G. van de POLL
*Department of Surgery, University Hospital Maastricht & Nutrition and Toxicology Research Institute Maastricht (NUTRIM), Maastricht University, 6200 AZ Maastricht, The Netherlands
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Cornelis H. C. Dejong;
Cornelis H. C. Dejong
*Department of Surgery, University Hospital Maastricht & Nutrition and Toxicology Research Institute Maastricht (NUTRIM), Maastricht University, 6200 AZ Maastricht, The Netherlands
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Marc A. J. G. Fischer;
Marc A. J. G. Fischer
†Department of Pharmacology and Toxicology, University Hospital Maastricht & Nutrition and Toxicology Research Institute Maastricht (NUTRIM), Maastricht University, 6200 AZ Maastricht, The Netherlands
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Aalt Bast;
Aalt Bast
†Department of Pharmacology and Toxicology, University Hospital Maastricht & Nutrition and Toxicology Research Institute Maastricht (NUTRIM), Maastricht University, 6200 AZ Maastricht, The Netherlands
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Ger H. Koek
‡Section of Gastroenterology/Hepatology, Department of Internal Medicine, University Hospital Maastricht, University Hospital Maastricht & Nutrition and Toxicology Research Institute Maastricht (NUTRIM), Maastricht University, 6202 AZ Maastricht, The Netherlands
Correspondence: Dr Ger H. Koek (email [email protected]).
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Publisher: Portland Press Ltd
Received:
September 07 2007
Revision Received:
October 23 2007
Accepted:
November 09 2007
Accepted Manuscript online:
November 09 2007
Online ISSN: 1470-8736
Print ISSN: 0143-5221
© The Authors Journal compilation © 2008 Biochemical Society
2008
Clin Sci (Lond) (2008) 114 (8): 553–560.
Article history
Received:
September 07 2007
Revision Received:
October 23 2007
Accepted:
November 09 2007
Accepted Manuscript online:
November 09 2007
Citation
Marcel C. G. van de POLL, Cornelis H. C. Dejong, Marc A. J. G. Fischer, Aalt Bast, Ger H. Koek; Decreased hepatosplanchnic antioxidant uptake during hepatic ischaemia/reperfusion in patients undergoing liver resection. Clin Sci (Lond) 1 April 2008; 114 (8): 553–560. doi: https://doi.org/10.1042/CS20070317
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