Cholestasis protects the liver from ischaemic injury and post- ischaemic inflammation in the mouse

Georgiev, P.; Navarini, A. A.; Eloranta, J. J.; Lang, K. S.; Kullak-Ublick, G. A.; Nocito, A.; Dahm, F.; Jochum, W.; Graf, R.; Clavien, P-A.
January 2007
Gut;Jan2007, Vol. 56 Issue 1, p121
Academic Journal
Background and hypothesis: Cholestasis is associated with high morbidity and mortality in patients undergoing major liver surgery, but the mechanisms responsible remain elusive. Increased ischaemic liver injury and inflammation may contribute to the poor outcome. Methods: Common bile duct ligation (biliary obstruction with hyperbilirubinaemia) or selective ligation of the left hepatic duct (biliary obstruction without hyperbilirubinaemia) was performed in C57BL/6 mice before 1 h of hepatic ischoemia and 1, 4 or 24 h of reperfusion. Infection with the intracellular hepatic pathogen Lisferia monocytogenes for 12 and 48 h was used to study ischaemia-independent hepatic inflammation. Results: Cholestatic mice showed considerable protection from ischaemic liver injury as determined by transaminase release, histological liver injury and neutrophil infiltration. In cholestatic mice, reduced in jury correlated with a failure to activate nuclear factor κB (NFκB) and tumour necrosis factor α (TNFα) mRNA synthesis, two key mediators of post-ischaemic liver inflammation. After selective bile duct ligation, both the ligated and the non-ligated lobes showed blocked activation of NFκB as well as reduced induction of TNFα mRNA synthesis and neutrophil infiltration. By contrast, infection with L monocytogenes showed comparable activation of NFκB and hepatic recruitment of neutrophils 12 h after infection. Conclusion: Cholestasis does not increase but rather dramatically protects the liver from ischaemic injury and inflammation. This effect is mediated by a systemic factor, but not bilirubin, and is associated with a preserved capacity to trigger an inflammatory response to other stimuli such as a bacterial pathogen.


Related Articles

  • The Protective Role of Steroids in Ischemia-Reperfusion Injury of the Liver. Pulitano, Carlo; Aldrighetti, Luca // Current Pharmaceutical Design;Feb2008, Vol. 14 Issue 5, p496 

    Liver ischemia-reperfusion injury occurs in a number of clinical settings, including liver surgery, transplantation, and circulatory shock, leading to significant morbidity and mortality. There is a substantial evidence that hepatic ischemia-reperfusion injury results from an intense...

  • Up-Regulation of Nerve Growth Factor in Cholestatic Livers and Its Hepatoprotective Role against Oxidative Stress. Tsai, Ming-Shian; Lin, Yu-Chun; Sun, Cheuk-Kwan; Huang, Shih-Che; Lee, Po-Huang; Kao, Ying-Hsien // PLoS ONE;Nov2014, Vol. 9 Issue 11, p1 

    The role of nerve growth factor (NGF) in liver injury induced by bile duct ligation (BDL) remains elusive. This study aimed to investigate the relationship between inflammation and hepatic NGF expression, to explore the possible upstream molecules up-regulating NGF, and to determine whether NGF...

  • Blunt Liver Injury in Children and Adults: Is There Really a Difference? KLAPHEKE, W. PATRICK; FRANKLIN, GLENN A.; Foley, David S.; Casos, Steven R.; Harbrecht, Brian G.; Richardson, J. David // American Surgeon;Sep2008, Vol. 74 Issue 9, p798 

    Hepatic injuries are increasingly managed nonoperatively with the availability of adjunctive procedures such as angiography, ERCP, and percutaneous drainage. Although extensively discussed in the adult population, little has been reported on outcomes and management of pediatric liver injury....

  • Assessment of preoperative exercise capacity in hepatocellular carcinoma patients with chronic liver injury undergoing hepatectomy. Masaki Kaibori; Morihiko Ishizaki; Kosuke Matsui; Richi Nakatake; Sakaguchi, Tatsuma; Daiki Habu; Sawako Yoshiuchi; Yutaka Kimura; A. Hon Kon // BMC Gastroenterology;2013, Vol. 13 Issue 1, p1 

    Background: Cardiopulmonary exercise testing measures oxygen uptake at increasing levels of work and predicts cardiopulmonary performance under conditions of stress, such as after abdominal surgery. Dynamic assessment of preoperative exercise capacity may be a useful predictor of postoperative...

  • Advances and changes in the management of liver injuries. Lee, Seong K.; Carrillo, Eddy H. // American Surgeon;Mar2007, Vol. 73 Issue 3, p201 

    Because of advances in noninvasive imaging techniques and a better understanding of the natural history of hepatic injuries; currently, most patients with complex liver injuries are treated in a nonoperative manner. Additionally, the availability of less invasive procedures has expanded...

  • Clinical application of soft polyglycolic acid felt for hemostasis and repair of a lacerated liver: Report of two cases. Markus Golling; Andre Schaudt; Arianeb Mehrabi; Zhoobin Mood; Wolf Bechstein // Surgery Today;Feb2008, Vol. 38 Issue 2, p188 

    Abstract  The mainstay of treatment for blunt or sharp liver trauma is conservative in 50%–80% of cases. When surgery is indicated, it is demanding and associated with substantial morbidity and mortality. Felt has been used extensively in cardiothoracic and vascular surgery to seal...

  • Surgical Management of Complex Liver Trauma: A Single Liver Transplant Center Experience. Petri, Sergio Li; Gruttadauria, Salvatore; Pagano, Duilio; Echeverri, Gabriel J.; Di Francesco, Fabrizio; Cintorino, Davide; Spada, Marco; Gridelli, Bruno // American Surgeon;Jan2012, Vol. 78 Issue 1, p20 

    Complex liver trauma often presents major diagnostic and management problems. Current operative management is mainly centered on packing, damage control, and early utilization of interventional radiology for angiography and embolization. In this retrospective observational study of patients...

  • Editorial Critique of Surgical Management of Complex Liver Trauma: A Single Liver Transplant Center Experience. Hiatt, Jonathan R. // American Surgeon;Jan2012, Vol. 78 Issue 1, p26 

    The author ponders on a report which described the clinical cases of 53 adult trauma patients with liver injuries. He argues in support of liver resection in treating severe liver trauma, and the participation of liver transplant surgeons in managing liver injuries. He adds that based on...

  • Protective Role of Genistein in Acute Liver Damage Induced by Carbon Tetrachloride. Kuzu, Nalan; Metin, Kerem; Dagli, Adile Ferda; Akdemir, Fatih; Orhan, Cemal; Yalniz, Mehmet; Ozercan, Ibrahim Hanifi; Sahin, Kazim; Bahcecioglu, Ibrahim Halil // Mediators of Inflammation;2007, Vol. 2007, Special section p1 

    Aim. In the present study, we investigated the protective effect of genistein in experimental acute liver damage induced by CCl4. Method. Forty rats were equally allocated to 5 groups. The first group was designated as the control group (group 1). The second group was injected with...


Read the Article


Sorry, but this item is not currently available from your library.

Try another library?
Sign out of this library

Other Topics