Induction of cellular resistance against Kupffer cell-derived oxidant stress: A novel concept of hepatoprotection by ischemic preconditioning

Schauer, Rolf; Gerbes, Alexander L.; Vonier, Daniel; Winkel, Mark op den; Fraunberger, Peter; Bilzer, Manfred

doi:10.1053/jhep.2003.50064

Cited by 60 publications

(38 citation statements)

References 48 publications

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“…Ischemic pre-conditioning is extensively documented to reduce I/R injury in a variety of organs including liver [10][11][12] . In our study, we demonstrated that IPC could attenuate hepatic I/R injury, indicated by reduced serum ALT and AST levels and improved tissue pathologic alteration as compared with I/R group.…”

Section: Discussionmentioning

confidence: 99%

Modulation of liver oxidant-antioxidant system by ischemic preconditioning during ischemia/reperfusion injury in rats

Yuan

Ma²,

Gong³

et al. 2005

WJG

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AIM:To investigate effects of ischemic pre-conditioning on the liver endogenous oxidant-antioxidant system during ischemia/reperfusion injury. METHODS:Twenty-four male Sprague-Dawley rats were randomly divided into sham-operated (Sham), ischemia/ reperfusion (I/R), ischemic pre-conditioning plus ischemia/ reperfusion (IPC) groups. Serum ALT, AST and hyaluronic acid levels were assayed and pathologic alterations observed. Liver malondialdehyde (MDA) contents, endogenous antioxidant enzymes, superoxidase dismutase (SOD), catalase (CAT), gultathionine peroxidase (GSH-Px) activities, neutrophils accumulation marker, myeloperoxidase (MPO) activities were measured respectively. RESULTS:Compared with I/R group, sinusoidal endothelial cells as well as hepatocytes damages, as assessed biochemically and histochemically, were improved significantly in IPC group; neutrophils infiltration was also markedly reduced. In IPC group, liver peroxidation, as measured by MDA contents, was significantly decreased when compared with I/R group; endogenous antioxidant enzymes, SOD, CAT and GSH-Px activities were markedly higher than that in I/R group. CONCLUSION:Ischemic pre-conditioning exerts protective effects on both hepatic sinusoidal endothelial cells and hepatocytes during liver I/R injury. Its mechanisms may involve dimunition of neutrophils infiltration and modulation of the imbalance of endogenous oxidant-antioxidant system in the organism.

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Section: Discussionmentioning

confidence: 99%

Modulation of liver oxidant-antioxidant system by ischemic preconditioning during ischemia/reperfusion injury in rats

Yuan

Ma²,

Gong³

et al. 2005

WJG

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“…The modulation of inflammatory response by hepatic IP has been also reported in different experimental models of warm and cold hepatic ischemia. IP reduces neutrophil accumulation, and the generation of ROS and proinflammatory cytokines including TNF and IL-1 from KC (13,97,98,108,109). The benefits of IP were also observed on hepatic microcirculation by inhibiting the effects of different vasoconstrictor mediators such as ETs, thus ameliorating sinusoidal perfusion and microvascular dysfunction (10,110).…”

Section: Steatosismentioning

confidence: 99%

The response of the hepatocyte to ischemia

Massip-Salcedo

Roselló-Catafau

Prieto

et al. 2007

Liver International

101

119

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Abstract:Background: Ischemia-reperfusion (I/R) injury associated with hepatic resections and liver transplantation remains a serious complication in clinical practice, in spite of several attempts to solve the problem. Aims: To evaluate the response of the hepatocyte to ischemia Methods: Published data are thus revised. Results: The response of the hepatocyte to ischemia is based on the sensitivity of hepatocytes to different types of ischemia, the kind of cell death of the hepatocyte when it is subjected to ischemia, and on the response of the hepatocyte to the different times and extents of ischemia. Clinical factors including starvation, graft, age, and hepatic steatosis, all of which contribute to enhancing liver susceptibility to ischemia/reperfusion injury. Conclusion: Ischemic preconditioning, based on the induction of a brief ischemia to the liver prior to a prolonged ischemia, has been applied in tumor hepatic resections for reducing hepatic I/R injury and recent clinical studies suggest that this surgical strategy could be appropriate for liver transplantation.

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“…To block KCs, a pretreatment with gadolinium chloride (GdCl 3 , 10 mg/kg b.w., 48 and 24 h before experiments) was performed in addition to LPS administration and after KC activation (n ¼ 5). 21 The LT receptor antagonist Ly171883 (20 mM, 30-60 min, n ¼ 5) and the TX receptor antagonist BM 13.177 (20 mM, 30-60 min, n ¼ 5) were given in addition to LPS pretreatment (1 mg/kg b.w., 3 h) and zymosan infusion (150 mg/ml, 40-46 min). The LT synthase inhibitor MK-886 (0.6 mg/kg b.w.)…”

Section: Induction Of Liver Fibrosis By Bile Duct Ligationmentioning

confidence: 99%

Intraperitoneal LPS amplifies portal hypertension in rat liver fibrosis

Steib¹,

Hartmann²,

Hesler³

et al. 2010

Laboratory Investigation

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Recent studies have shown that the risk of variceal bleeding in patients with liver cirrhosis increases with infections such as spontaneous bacterial peritonitis (SBP). In this study, we hypothesized that pretreatment with intraperitoneal LPS may escalate portal hypertension. In fibrotic livers (4 weeks after bile duct ligation, BDL), the activation of Kupffer cells (KCs) by zymosan (150 mg/ml) in the isolated non-recirculating liver perfusion system resulted in a transient increase in portal perfusion pressure. Pretreatment with intraperitoneal LPS (1 mg/kg body weight (b.w.) for 3 h) increased basal portal perfusion pressure, and prolonged the zymosan-induced increase from transient to a long-lasting increase that was sustained until the end of the experiments in BDL but not in sham-operated animals. Pretreatment with gadolinium chloride (10 mg/kg b.w.), MK-886 (0.6 mg/kg b.w.), Ly171883 (20 mM) or BM 13.177 (20 mM) reduced the maximal and long-lasting pressure increase in BDL animals by approximately 50-60%. The change in portal perfusion pressure was paralleled by a long-lasting production of cysteinyl leukotriene (Cys-LT) and thromboxane (TX) after LPS pretreatment. However, the response to vasoconstrictors was not altered by intraperitoneal LPS. Western blot analyses showed an increased Toll-like receptor (TLR)4 and MyD88 expression after LPS pretreatment. In vivo experiments confirmed that intraperitoneal LPS increased basal portal pressure, and extended the portal pressure increase produced by intraportal zymosan or by LPS infusion. In conclusion, upregulation of TLR4 and MyD88 expression in fibrotic livers confers hypersensitivity to LPS. This may lead to escalation of portal hypertension by production of TX and Cys-LT after endotoxin-induced KC activation. Therefore, LT inhibitors may represent a promising treatment option in addition to early administration of antibiotics in SBP.

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Induction of cellular resistance against Kupffer cell-derived oxidant stress: A novel concept of hepatoprotection by ischemic preconditioning

Cited by 60 publications

References 48 publications

Modulation of liver oxidant-antioxidant system by ischemic preconditioning during ischemia/reperfusion injury in rats

Modulation of liver oxidant-antioxidant system by ischemic preconditioning during ischemia/reperfusion injury in rats

The response of the hepatocyte to ischemia

Intraperitoneal LPS amplifies portal hypertension in rat liver fibrosis

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