Reduction of Liver Ischemia-Reperfusion Injury Via Glutamine Pretreatment

Stangl, Rita; Szíjártó, Attila; Ónody, Péter; Tamás, Judit; Tátrai, Miklós; Hegedüs, V; Blázovics, Anna; Lotz, Gábor; Kiss, András; Módis, Katalin; Gerö, Domokos; Szabó, Csaba; Kempler, Péter; Harsányi, László

doi:10.1016/j.jss.2009.09.047

Cited by 22 publications

(18 citation statements)

References 48 publications

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“…We recently also reported the cytoprotective effect of glutamine on anoxia/reoxygenation injury (an in vitro model of I/R injury) of renal tubular epithelial cells [19]. Moreover, many studies demonstrated the protective effect of glutamine in liver I/R injury [28][29][30]. How- ever, the mechanisms of how glutamine showed protection against liver I/R injury were not clearly demonstrated.…”

Section: Discussionmentioning

confidence: 99%

Tissue-Protective Effect of Glutamine on Hepatic Ischemia-Reperfusion Injury via Induction of Heme Oxygenase-1

Zhang¹,

Shi²,

Yu³

et al. 2013

Pharmacology

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Background/Aims: Glutamine showed cytoprotective activity in vitro on anoxia-reoxygenation injury via induction of heme oxygenase-1 (HO-1). We thus investigated its in vivo tissue-protective effect in a rat liver ischemia-reperfusion (I/R) model. Methods: Before the I/R procedure, animals were treated with glutamine. Liver injury was evaluated by serum liver enzymes, histological examination and apoptosis detection by transferase-mediated uridine nick end labeling staining. Meanwhile, expression and activities of HO-1 were measured by Western blot and a biochemical method. Liver blood flow was measured by using a laser Doppler flowmeter, and oxidative injury was investigated by the thiobarbituric acid-reactive substance (TBARS) assay. The inflammatory cytokine monocyte chemotactic protein (MCP)-1 was quantified by ELISA. Results: I/R caused a large increase in levels of liver enzymes, remarkably inducing the necrosis and apoptosis of liver tissue, which was markedly inhibited by glutamine, during which HO-1 was upregulated significantly, and the HO-1 inhibitor zinc protoporphyrin nullified the effect of glutamine. Liver blood flow was greatly reduced after I/R; however, it was significantly improved by glutamine. Lipid peroxidation (TBARS) in liver tissue was largely induced which was significantly lowered by glutamine. Similar results were also observed for the production of MCP-1. Conclusion: Glutamine protected tissue against oxidative injury during rat hepatic I/R, by induction of HO-1 to fulfill antioxidative and antiapoptotic effects.

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Section: Discussionmentioning

confidence: 99%

Tissue-Protective Effect of Glutamine on Hepatic Ischemia-Reperfusion Injury via Induction of Heme Oxygenase-1

Zhang¹,

Shi²,

Yu³

et al. 2013

Pharmacology

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“…Intravenous infusions of LOLA likewise result in significant increases of plasma glutamate and restoration of glutamine in patients with chronic liver disease [14]. Restoration of the synthesis of glutamine in liver may represent an important step implicated in the hepatoprotective properties of LOLA in NAFLD/ NASH in view of the observations that administration of glutamine results in improvement of hepatic injury caused by a range of insults including ischemia/reperfusion injury and that resulting from chronic alcohol ingestion [15,16]. More recently, reports from 2 studies in experimental NAFLD/NASH demonstrate significant hepatoprotective effects of glutamine [17,18].…”

Section: Glutaminementioning

confidence: 99%

Hepatoprotection by L-Ornithine L-Aspartate in Non-Alcoholic Fatty Liver Disease

Butterworth

Canbay

2018

Dig Dis

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Background: Non-alcoholic fatty liver disease (NAFLD) is the leading chronic hepatic condition worldwide and new approaches to management and treatment are limited. Summary: L-ornithine L-aspartate (LOLA) has hepatoprotective properties in patients with fatty liver of diverse etiology and results of a multicenter randomized clinical trial reveal that 12 weeks treatment with oral LOLA (6–9 g/d) results in a dose-related reduction in activities of liver enzymes and triglycerides together with significant improvements of liver/spleen CT ratios. A preliminary report described improvements of hepatic microcirculation in patients with non-alcoholic steatohepatitis (NASH) following treatment with LOLA. Mechanisms responsible for the beneficial effects of LOLA in NAFLD/NASH involve, in addition to its established ammonia-lowering effect, metabolic transformations of the LOLA-constituent amino acids L-ornithine and L-aspartate into L-glutamine, L-arginine, and glutathione. These metabolites have well-established actions implicated in the prevention of lipid peroxidation, improvement of hepatic microcirculation in addition to anti-inflammatory, and anti-oxidant properties. Key Messages: (1) LOLA is effective for the treatment of key indices in NAFLD/NASH. (2) Mechanisms other than LOLA’s ammonia-lowering action have been postulated. (3) Further assessments in the clinical setting are now required.

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“…For rodents, some reports have demonstrated that pretreatment with Gln helps to reduce I/R injury in a variety of organs by using different I/R animal models [11,17,18,19,20]. Nevertheless, few studies have been carried out on this topic using the obstructive jaundice hepatic I/R model.…”

Section: Introductionmentioning

confidence: 99%

Preconditioning with Glutamine Protects against Ischemia/Reperfusion-Induced Hepatic Injury in Rats with Obstructive Jaundice

Dai

Peng

et al. 2014

Pharmacology

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Objective: To ascertain whether glutamine (Gln) pretreatment protects rats with obstructive jaundice from hepatic ischemia/reperfusion (I/R) injury and to determine the underlying molecular mechanisms. Methods: An obstructive jaundice rat model was developed by bile duct ligation. On the first day after the operation, all rats were randomized into two groups and received oral Gln or normal saline (NS) daily for 7 days. Then both groups underwent a 15-min liver ischemia via the Pringle maneuver. Blood samples as well as liver and intestinal tissues were harvested and measured after 1, 6 and 24 h of reperfusion. Results: The results showed that the histological morphology of the liver and intestinal tissues significantly improved in the Gln group after I/R injury compared with the NS group. Serum proteins and enzymes associated with hepatic function also significantly improved in the Gln group. The level of glutathione increased and the levels of malondialdehyde and myeloperoxidase decreased in the Gln group. The levels of interleukin-1β and tumor necrosis factor-α decreased in the Gln group. Moreover, bcl-2 protein expression was upregulated and intercellular adhesion molecule 1 and bax protein expression downregulated in the Gln group; the caspase 3 mRNA level significantly increased in the Gln group. Conclusions: The study demonstrates that preconditioning with Gln significantly improves hepatic structure and function after I/R injury in rats with obstructive jaundice. The protective effect of Gln was mediated by the inhibition of reactive oxygen species and inflammation as well as a reduction in hepatocyte apoptosis.

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Reduction of Liver Ischemia-Reperfusion Injury Via Glutamine Pretreatment

Cited by 22 publications

References 48 publications

Tissue-Protective Effect of Glutamine on Hepatic Ischemia-Reperfusion Injury via Induction of Heme Oxygenase-1

Tissue-Protective Effect of Glutamine on Hepatic Ischemia-Reperfusion Injury via Induction of Heme Oxygenase-1

Hepatoprotection by L-Ornithine L-Aspartate in Non-Alcoholic Fatty Liver Disease

Preconditioning with Glutamine Protects against Ischemia/Reperfusion-Induced Hepatic Injury in Rats with Obstructive Jaundice

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