Taurine Protects from Liver Injury after Warm Ischemia in Rats: The Role of Kupffer Cells

Kinčius, Marius; Liang, Rui; Nickkholgh, Arash; Hoffmann, Katrin; Flechtenmacher, Christa; Ryschich, Eduard; Gutt, Carsten N.; Gebhard, Martha-Maria; Schmidt, Joachim; Büchler, Markus W.; Schemmer, Peter

doi:10.1159/000102982

Cited by 30 publications

(36 citation statements)

References 70 publications

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“…Moreover, the macrophages of taut Ϫ/Ϫ mice appear to change their stability in response to malaria, as circumstantially indicated by the increased systemic levels of TNF-␣ and IL-1␤, which are produced primarily by macrophages. This accords with other data showing, conversely, that taurine is able to dampen the effect of proinflammatory cytokines, including IL-1␤ (12) and TNF-␣ (10,24,33,34,44,47,60).…”

Section: Discussionsupporting

confidence: 92%

Loss of Ability To Self-Heal Malaria upon Taurine Transporter Deletion

et al. 2010

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Deletion of the taurine transporter gene (taut) results in lowered levels of taurine, the most abundant amino acid in mammals. Here, we show that taut ؊/؊ mice have lost their ability to self-heal blood-stage infections with Plasmodium chabaudi malaria. All taut ؊/؊ mice succumb to infections during crisis, while about 90% of the control taut ؉/؉ mice survive. The latter retain unchanged taurine levels even at peak parasitemia. Deletion of taut, however, results in the lowering of circulating taurine levels from 540 to 264 mol/liter, and infections cause additional lowering to 192 mol/liter. Peak parasitemia levels in taut ؊/؊ mice are approximately 60% higher than those in taut ؉/؉ mice, an elevation that is associated with increased systemic tumor necrosis factor alpha (TNF-␣) and interleukin-1␤ (IL-1␤) levels, as well as with liver injuries. The latter manifest as increased systemic ammonia levels, a perturbed capacity to entrap injected particles, and increased expression of genes encoding TNF-␣, IL-1␤, IL-6, inducible nitric oxide synthase (iNOS), NF-B, and vitamin D receptor (VDR). Autopsy reveals multiorgan failure as the cause of death for malaria-infected taut ؊/؊ mice. Our data indicate that taut-controlled taurine homeostasis is essential for resistance to P. chabaudi malaria. Taurine deficiency due to taut deletion, however, impairs the eryptosis of P. chabaudi-parasitized erythrocytes and expedites increases in systemic TNF-␣, IL-1␤, and ammonia levels, presumably contributing to multiorgan failure in P. chabaudi-infected taut ؊/؊ mice.

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Section: Discussionsupporting

confidence: 92%

Loss of Ability To Self-Heal Malaria upon Taurine Transporter Deletion

et al. 2010

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“…ROS lead to oxidative damage, induction of p53, apoptosis and necrosis of hepatocytes and endothelial cells. The late phase (6-48 h after reperfusion) is characterized by neutrophil-mediated inflammatory responses 23,31,32,[34][35][36][37][38][39][40] . Thus, pathways regulating the cellular redox equilibrium, p53-dependent apoptosis and cellular death receptors represent potential targets for novel pharmaceutical interventions to protect hepatocytes fromIRI-induced cell death.…”

Section: Discussionmentioning

confidence: 99%

Neutralization of CD95 ligand protects the liver against ischemia-reperfusion injury and prevents acute liver failure

et al. 2018

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Ischemia-reperfusion injury is a common pathological process in liver surgery and transplantation, and has considerable impact on the patient outcome and survival. Death receptors are important mediators of ischemiareperfusion injury, notably the signaling pathways of the death receptor CD95 (Apo-1/Fas) and its corresponding ligand CD95L. This study investigates, for the first time, whether the inhibition of CD95L protects the liver against ischemia-reperfusion injury. Warm ischemia was induced in the median and left liver lobes of C57BL/6 mice for 45 min. CD95Fc, a specific inhibitor of CD95L, was applied prior to ischemia. Hepatic injury was assessed via consecutive measurements of liver serum enzymes, histopathological assessment of apoptosis and necrosis and caspase assays at 3, 6, 12, 18 and 24 h after reperfusion. Serum levels of liver enzymes, as well as characteristic histopathological changes and caspase assays indicated pronounced features of apoptotic and necrotic liver damage 12 and 24 h after ischemiareperfusion injury. Animals treated with the CD95L-blocker CD95Fc, exhibited a significant reduction in the level of serum liver enzymes and showed both decreased histopathological signs of parenchymal damage and decreased caspase activation. This study demonstrates that inhibition of CD95L with the CD95L-blocker CD95Fc, is effective in protecting mice from liver failure due to ischemia-reperfusion injury of the liver. CD95Fc could therefore emerge as a new pharmacological therapy for liver resection, transplantation surgery and acute liver failure.

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“…Various experiments have already been performed to investigate the protective effects of taurine on IRI in different tissues [5,6,[13][14][15][16]. However, the responsible mechanisms for the cyto-and organ-protective effects of taurine are only partly understood.…”

Section: Discussionmentioning

confidence: 99%

“…In the experiment group, donors were given 1.5 mL of intravenous taurine solution (TAU) (Department of Pharmacy, Ruprecht-Karls University, Heidelberg, Germany) via inferior vena cava 10 min before left donor nephrectomy for transplantation. Three different concentrations of taurine (30, 100, 300 mM) were administered in three different experiment groups (i.e., each experiment group received a certain amount of taurine different from the other groups) as described previously [6]. Controls were given the same volume of Ringer's solution.…”

Section: Treatment Experimental Designmentioning

confidence: 99%

“…Up to now, many studies have documented the protective effects of taurine against an array of damaging stimuli, including ischemia/reperfusion (I/R), hyperglycemia, reactive oxygen species, heat shock, toxic xenobiotics, cellular excitotoxicity, and osmotic derangements [4]. Most recently, taurine has been clearly demonstrated to improve graft survival after cold ischemia and subsequent liver transplantation [5], and to protect livers from warm I/R [6] and hearts from myocardial infarction in rats [7]. However, to date, limited information is available regarding the relationship between taurine and kidney I/R.…”

Section: Introductionmentioning

confidence: 99%

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