Anti-Inflammatory Pre-Treatment to Reduce Mobilization-Induced Liver Inflammation in Mice: Novel Model to Study Liver Injury

T. Hendrikx; C. Piersma; D. K. Dhar; L. Mpabanzi; J. J. W. Schreurs; M. Malagó; R. Shiri-Sverdlov; S. W. M. Olde Damink

doi:10.4236/mri.2015.41001

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Anti-Inflammatory Pre-Treatment to Reduce Mobilization-Induced Liver Inflammation in Mice: Novel Model to Study Liver Injury

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DOI: 10.4236/mri.2015.41001 2,892 Downloads 3,342 Views

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T. Hendrikx^1,2, C. Piersma³, D. K. Dhar^4,5, L. Mpabanzi^2,3, J. J. W. Schreurs^1,2, M. Malagó⁴, R. Shiri-Sverdlov^1,2, S. W. M. Olde Damink^2,3,4*

Affiliation(s)

¹Department of Molecular Genetics, Maastricht University, Maastricht, The Netherlands.
²Nutrition and Toxicology Research Institute Maastricht, Maastricht University, Maastricht, The Netherlands.
³Department of Surgery, Maastricht University Medical Centre, Maastricht, The Netherlands.
⁴Department of HPB Surgery and Liver Transplantation, Royal Free Hospital, University College London, London, UK.
⁵Comparative Medicine Department, Organ Transplantation Center, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia.

ABSTRACT

Background: Liver surgery requires mobilization of the liver resulting in injury. Mobilization is the predominant cause of hepatocyte damage during liver surgery and jeopardizes post-operative liver function. Previously, mobilization-induced liver injury was found to be associated with inflammation. So far, anti-inflammatory drugs to potentially prevent liver inflammation following liver mobilization were not tested. In this study, we aimed to establish an in vivo mouse model of mobilization-induced liver injury and to evaluate the effect of anti-inflammatory pre-treatment before liver mobilization on liver inflammation. Methods: To develop a mouse model for mobilization-induced liver injury, C57BL/6 mice (n = 8) underwent surgery during which the liver was mobilized by gentle manipulation of the lobes with cotton-wool applicators for 15 minutes. In two control groups, the liver was left alone or was subjected to laparotomy only. An additional group was added that received anti-TNF treatment (Infliximab) 2 days prior to surgery. Liver samples were obtained 2 hours after mobilization and liver inflammation was analyzed by histology and inflammatory gene expression. Results: Gentle liver mobilization resulted in acute liver inflammation as indicated by increased recruitment of inflammatory cells and elevated inflammatory gene expression compared to controls. Infliximab pre-treatment had no effect on the inflammatory response in the liver. Conclusion: Our current model provides an excellent opportunity to study the effects of pre-treatment with anti-inflammatory drugs on mobilization-induced liver inflammation. Further studies are needed to investigate whether anti-inflammatory mediators can be used to prevent liver inflammation.

KEYWORDS

Liver Surgery, Hepatocellular Damage, Inflammation, Translational Model, Post-Resectional Liver Failure

Conflicts of Interest

The authors declare no conflicts of interest.

Cite this paper

Hendrikx, T. , Piersma, C. , Dhar, D. , Mpabanzi, L. , Schreurs, J. , Malagó, M. , Shiri-Sverdlov, R. and Damink, S. (2015) Anti-Inflammatory Pre-Treatment to Reduce Mobilization-Induced Liver Inflammation in Mice: Novel Model to Study Liver Injury. Modern Research in Inflammation, 4, 1-7. doi: 10.4236/mri.2015.41001.

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