Dietary glycine blunts liver injury after bile duct ligation in rats

Froh, Matthias; Zhong, Zhi; Walbrun, Peter; Lehnert, Mark; Netter, Susanne; Wiest, Reiner; Conzelmann, Lars O.; Gäbele, Erwin; Hellerbrand, Claus; Schölmerich, Jürgen; Thurman, Ronald G.

doi:10.3748/wjg.14.5996

Cited by 14 publications

(10 citation statements)

References 47 publications

(67 reference statements)

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“…5, P4) 4 days after toxication. Recent research has indicated that glycine significantly decreases liver injury via a direct effect on hepatocytes (Froh et al 2008). As the decreased hepatic glycine level was normalized by DG at both the 1st and 4th day after injury, we presumed that the elevation of glycine in the urine may be beneficial to the recovery of hepatic cells.…”

Section: Metabolite Variation Induced By CCLmentioning

confidence: 93%

Metabolic profiling reveals the protective effect of diammonium glycyrrhizinate on acute hepatic injury induced by carbon tetrachloride

et al. 2010

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Section: Metabolite Variation Induced By CCLmentioning

confidence: 93%

Metabolic profiling reveals the protective effect of diammonium glycyrrhizinate on acute hepatic injury induced by carbon tetrachloride

et al. 2010

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“…Kupffer cells were isolated as per the protocol by Froh et al [17]. Qualitative screening for Kupffer cells was carried out with immunoreactivity against a CD68 antibody.…”

Section: Methodsmentioning

confidence: 99%

“…Mouse non-parenchymal cells (mostly Kupffer cells) were isolated as per Froh et al [17]. Cells were washed and plated in 35mm 2 dishes using 10% FBS containing DMEM with mouse recombinant leptin (500ng/ml).…”

Section: Methodsmentioning

confidence: 99%

Leptin is key to peroxynitrite-mediated oxidative stress and Kupffer cell activation in experimental non-alcoholic steatohepatitis

Chatterjee¹,

Ganini²,

Tokar³

et al. 2013

Journal of Hepatology

112

103

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Background and Aims Progression from steatosis to steatohepatitic lesions is hypothesized to require a second hit. These lesions have been associated with increased oxidative stress, often ascribed to high levels of leptin and other proinflammatory mediators. Here we have examined the role of leptin in inducing oxidative stress and Kupffer cell activation in CCl4-mediated steatohepatitic lesions of obese mice. Methods Male C57BL/6 mice fed with a high fat diet (60%kcal) at 16 weeks were administered CCl4 to induce steatohepatitic lesions. Approaches included use of immuno-spin trapping for measuring free radical stress, gene-deficient mice for leptin, p47 phox, iNOS and adoptive transfer of leptin primed macrophages in vivo. Results Diet-induced obese (DIO) mice, treated with CCl4 increased serum leptin levels. Oxidative stress was significantly elevated in DIO mice liver but not in OB/OB mice, or in DIO mice treated with leptin antibody. In OB/OB mice, leptin supplementation restored markers of free radical generation. Markers of free radical formation were significantly decreased by the peroxynitrite decomposition catalyst FeTPPS, the iNOS inhibitor 1400W, the NADPH oxidase inhibitor apocynin, or in iNOS or p47 phox-deficient mice. These results correlated with the decreased expression of TNF-alpha and MCP-1. Kupffer cell depletion eliminated oxidative stress and inflammation, whereas in macrophage-depleted mice, the adoptive transfer of leptin-primed macrophages significantly restored inflammation. Conclusions These results, for the first time, suggest that leptin action in macrophages of steatotic liver through induction of iNOS and NADPH oxidase caused peroxynitrite-mediated oxidative stress thus activating Kupffer cells.

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“…This leads to a more homogeneous reperfusion with less injury to the vascular system revealed by decreased sinusoidal dilation and indirectly by improved liver histology and decreased cell apoptosis in the glycine‐treated groups. An added profit during the perfusion by continuous glycine supplication to the perfusate was postulated based on the reported reduced vulnerability during a glycine‐enriched diet . However, the effect of hyperpolarization on Kupffer cells may also be transient.…”

Section: Discussionmentioning

confidence: 99%

“…An added profit during the perfusion by continuous glycine supplication to the perfusate was postulated based on the reported reduced vulnerability during a glycine-enriched diet. (37,38) However, the effect of hyperpolarization on Kupffer cells may also be transient. The lack of a suitable control, which had only been treated with donor organ glycine application but not continuous perfusate supplication, will be addressed in future studies.…”

Section: Discussionmentioning

confidence: 99%

Improvement of Normothermic Ex Vivo Machine Perfusion of Rat Liver Grafts by Dialysis and Kupffer Cell Inhibition With Glycine

et al. 2019

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Normothermic ex vivo liver machine perfusion might be a superior preservation strategy for liver grafts from extended criteria donors. However, standardized small animal models are not available for basic research on machine perfusion of liver grafts. A laboratory‐scaled perfusion system was developed consisting of a custom‐made perfusion chamber, a pressure‐controlled roller pump, and an oxygenator. Male Wistar rat livers were perfused via the portal vein for 6 hours using oxygenated culture medium supplemented with rat erythrocytes. A separate circuit was connected via a dialysis membrane to the main circuit for plasma volume expansion. Glycine was added to the flush solution, the perfusate, and the perfusion circuit. Portal pressure and transaminase release were stable over the perfusion period. Dialysis significantly decreased the potassium concentration of the perfusate and led to significantly higher bile and total urea production. Hematoxylin‐eosin staining and immunostaining for single‐stranded DNA and activated caspase 3 showed less sinusoidal dilatation and tissue damage in livers treated with dialysis and glycine. Although Kupffer cells were preserved, tumor necrosis factor α messenger RNA levels were significantly decreased by both treatments. For proof of concept, the optimized perfusion protocol was tested with donation after circulatory death (DCD) grafts, resulting in significantly lower transaminase release into the perfusate and preserved liver architecture compared with baseline perfusion. In conclusion, our laboratory‐scaled normothermic portovenous ex vivo liver perfusion system enables rat liver preservation for 6 hours. Both dialysis and glycine treatment were shown to be synergistic for preservation of the integrity of normal and DCD liver grafts.

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Dietary glycine blunts liver injury after bile duct ligation in rats

Abstract: Abstract

Cited by 14 publications

References 47 publications

Metabolic profiling reveals the protective effect of diammonium glycyrrhizinate on acute hepatic injury induced by carbon tetrachloride

Metabolic profiling reveals the protective effect of diammonium glycyrrhizinate on acute hepatic injury induced by carbon tetrachloride

Leptin is key to peroxynitrite-mediated oxidative stress and Kupffer cell activation in experimental non-alcoholic steatohepatitis

Improvement of Normothermic Ex Vivo Machine Perfusion of Rat Liver Grafts by Dialysis and Kupffer Cell Inhibition With Glycine

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