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Ischemic preconditioning improves liver regeneration by sustaining energy metabolism after partial hepatectomy under ischemia in rats

Authors

  • Mustafa Kerem,

    1. Departments of 1General Surgery2Biochemistry, Faculty of Medicine, Gazi University, Ankara, Turkey3Department of Pathology, Faculty of Medicine, Erciyes University, Kayseri
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  • 1 Abdulkadir Bedirli,

    1. Departments of 1General Surgery2Biochemistry, Faculty of Medicine, Gazi University, Ankara, Turkey3Department of Pathology, Faculty of Medicine, Erciyes University, Kayseri
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  • 1 Ebru Ofluoglu,

    1. Departments of 1General Surgery2Biochemistry, Faculty of Medicine, Gazi University, Ankara, Turkey3Department of Pathology, Faculty of Medicine, Erciyes University, Kayseri
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  • 2 Kemal Deniz,

    1. Departments of 1General Surgery2Biochemistry, Faculty of Medicine, Gazi University, Ankara, Turkey3Department of Pathology, Faculty of Medicine, Erciyes University, Kayseri
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  • 3 Nurten Turkozkan,

    1. Departments of 1General Surgery2Biochemistry, Faculty of Medicine, Gazi University, Ankara, Turkey3Department of Pathology, Faculty of Medicine, Erciyes University, Kayseri
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  • 2 Hatice Pasaoglu,

    1. Departments of 1General Surgery2Biochemistry, Faculty of Medicine, Gazi University, Ankara, Turkey3Department of Pathology, Faculty of Medicine, Erciyes University, Kayseri
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  • and 2 Omer Sakrak 1

    1. Departments of 1General Surgery2Biochemistry, Faculty of Medicine, Gazi University, Ankara, Turkey3Department of Pathology, Faculty of Medicine, Erciyes University, Kayseri
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Mustafa Kerem, MD, Department of General Surgery, Faculty of Medicine, Gazi University, Besevler 06510, Ankara, Turkey.
Tel: +90 312 2025727
Fax: +90 312 2124647
e-mail: mkerem@gazi.edu.tr

Abstract

Abstract: Background: The protective effect of ischemic preconditioning (IPC) has been reported on improvement of survival, reduction of liver necrosis and enhancement of the regenerative capacity of hepatocytes after partial hepatectomy. This study was undertaken to confirm that IPC has a significant impact on regeneration of hepatocytes after partial hepatectomy in ischemically damaged liver. In addition, we sought to examine the role of adenine nucleotides in this process.

Methods: Wistar rats were subjected to 60 min of total hepatic ischemia, followed by 70% hepatectomy. The animals were subdivided into an IPC (10/15 min) group and a non-IPC (control) group. Liver function tests and arginase activity were analyzed. Hepatic adenosine triphosphate (ATP), adenosine diphosphate and adenosine monophosphate were measured using gradient high-performance liquid chromatography. The liver regeneration was identified using relative liver weight and proliferating cell nuclear antigen (PCNA) labeling index.

Results: IPC treatment improved serum liver enzymes and tissue arginase activity (P<0.05) when compared with the control group. The preconditioned livers were associated with upregulation of ATP expression and also increased tissue energy charge. Regenerated liver weight in the IPC group was significantly higher than in the control group (P<0.05). The PCNA labeling index in the remnant livers in the IPC group was also significantly increased at 24 and 48 h after partial hepatectomy (P<0.05).

Conclusion: These results suggest that IPC-augmented liver regeneration after hepatectomy, probably due to the stabilization of energy metabolism in rats.

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