Acute Hyperglycemia Worsens Hepatic Ischemia/Reperfusion Injury in Rats

Department of Anesthesia and Perioperative Care, University of California San Francisco, San Francisco, CA 94143-0648, USA.
Journal of Gastrointestinal Surgery (Impact Factor: 2.8). 12/2009; 14(3):528-35. DOI: 10.1007/s11605-009-1112-3
Source: PubMed

ABSTRACT Acute hyperglycemia is known to worsen ischemia/reperfusion (I/R) injury following myocardial infarction and stroke. We investigated whether acute hyperglycemia worsens injury and amplifies the inflammatory response evoked by hepatic I/R.
Rats were pretreated with an intraperitoneal injection of 25% glucose or 0.9% sodium chloride (10 ml/kg BW). Subsequently, rats underwent partial (70%) hepatic ischemia for 45 min. After 4 h of reperfusion, hepatic injury, oxidative stress, inflammation, and heat shock protein expression were assessed.
Liver injury was increased in the hyperglycemic group with alanine aminotransferase (ALT) and aspartate aminotransferease (AST) serum concentrations of 7,832 +/- 3,374 and 10,677 +/- 4,110 U/L compared to 3,245 +/- 2,009 and 5,386 +/- 3,393 U/L (p < 0.05 vs. control). Hyperglycemic I/R was associated with increased liver nitrotyrosine concentrations and increased neutrophil infiltration. I/R upregulated the protective heat shock proteins HSP32 and HSP70 in control animals, but this protective mechanism was inhibited by hyperglycemia: HSP32 expression decreased from 1.97 +/- 0.89 (control) to 0.46 +/- 0.13 (hyperglycemia), HSP70 expression decreased from 18.99 +/- 11.55 (control) to 3.22 +/- 0.56 (hyperglycemia), (expression normalized to sham, both p < 0.05 vs. control I/R).
Acute hyperglycemia worsens hepatic I/R injury by amplifying oxidative stress and the inflammatory response to I/R. The increase in injury is associated with a downregulation of the protective heat shock proteins HSP32 and HSP70.

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Available from: Graciela Martinez-Palli, Feb 21, 2014
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    • "It was reported that postoperative glucose concentration was associated with the extent of hepatic injury in hepatectomized patients [10]. A recent animal study in rats has demonstrated that acute hyperglycemia for a transient period amplifies hepatic ischemia reperfusion injury, which suggests the importance of acute hyperglycemia which occurs during surgery when hepatic ischemia injury may be accompanied [11]. However, the relationship between intraoperative hyperglycemia and hepatic injury has never been assessed in clinical liver resection. "
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    ABSTRACT: Background Patients undergoing liver resection are at risk for intraoperative hyperglycemia and acute hyperglycemia is known to induce hepatocytes injury. Thus, we aimed to evaluate whether intraoperative hyperglycemia during liver resection is associated with the extent of hepatic injury. Methods This 1 year retrospective observation consecutively enrolled 85 patients undergoing liver resection for hepatocellular carcinoma. Blood glucose concentrations were measured at predetermined time points including every start/end of intermittent hepatic inflow occlusion (IHIO) via arterial blood analysis. Postoperative transaminase concentrations were used as surrogate parameters indicating the extent of surgery-related acute hepatocytes injury. Results Thirty (35.5%) patients developed hyperglycemia (blood glucose > 180 mg/dl) during surgery. Prolonged (≥ 3 rounds) IHIO (odds ratio [OR] 7.34, P = 0.004) was determined as a risk factors for hyperglycemia as well as cirrhosis (OR 4.07, P = 0.022), lower prothrombin time (OR 0.01, P = 0.025), and greater total cholesterol level (OR 1.04, P = 0.003). Hyperglycemia was independently associated with perioperative increase in transaminase concentrations (aspartate transaminase, β 105.1, standard error 41.7, P = 0.014; alanine transaminase, β 81.6, standard error 38.1, P = 0.035). Of note, blood glucose > 160 or 140 mg/dl was not associated with postoperative transaminase concentrations. Conclusions Hyperglycemia during liver resection might be associated with the extent of hepatocytes injury. It would be rational to maintain blood glucose concentration < 180 mg/dl throughout the surgery in consideration of parenchymal disease, coagulation status, lipid profile, and the cumulative hepatic ischemia in patients undergoing liver resection for hepatocellular carcinoma.
    PLoS ONE 10/2014; 9(10):e109120. DOI:10.1371/journal.pone.0109120 · 3.23 Impact Factor
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    ABSTRACT: We investigated the effect of glucose on hypoxic death of rat cardiomyocyte-derived H9c2 cells and found that there is an optimal glucose concentration for protection against hypoxic cell death. Hypoxic cell death in the absence of glucose is accompanied by rapid ATP depletion, release of apoptosis-inducing factor from mitochondria, and nuclear chromatin condensation, all of which are inhibited by glucose in a dose-dependent manner. In contrast, excessive glucose also induces hypoxic cell death that is not accompanied by these events, suggesting a change in the mode of cell death between hypoxic cells with and without glucose supplementation.
    Biochemical and Biophysical Research Communications 06/2010; 396(3):614-8. DOI:10.1016/j.bbrc.2010.04.122 · 2.30 Impact Factor
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    ABSTRACT: Background: Glutamine (Gln) supplementation is known to decrease oxidative stress and inflammatory response, enhance resistance to infectious pathogens, shorten hospital stay, and decrease medical costs of patients. This study was undertaken to evaluate the relationship between the effect of early parenteral glutamine (Gln) supplement on acute liver injury (ALI) and heat shock protein 70 (HSP-70) expression in critical patients. Methods: Forty-four patients who had been admitted to the emergency intensive care unit (EICU) of Nanjing First Hospital Affiliated to Nanjing Medical University were randomly divided into a control group (n=22) and a Gln group (n=22). The patients of the two groups received enteral and parenteral nutrition. In addition, parenteral Gln 0.4 g/kg per day was given for 7 days in the Gln group. Serum HSP-70 and Gln were measured at admission and at 7 days after admission. Serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), and total bilirubin (TBiL), serum levels of HSP-70 and Gln, mechanical ventilation (MV) time, ICU stay, peripheral blood of TNF-α, IL-6, CD3, CD4 and CD4/CD8 levels were also measured in the two groups. Results: In the Gln group, the levels of serum HSP-70 and Gln were significantly higher after Gln treatment than those before the treatment (P<0.01). HSP-70 level was positively correlated with the Gln level in the Gln group after administration of parenteral Gln (P<0.01). The levels of serum ALT, AST, TBiL and TNF-α, IL-6 were lower in the Gln group than in the non-Gln group (P<0.01). MV time and ICU stay were significantly different between the two groups (P<0.05). The levels of CD3, CD4 and CD4/CD8 were significantly higher in the Gln group than in the control group after treatment (P<0.05). Conclusion: Parenteral Gln significantly increases the level of serum HSP70 in critically ill patients. The enhanced expression of HSP70 is correlated with improved outcomes of Gln-treated patients with acute liver injury.
    01/2011; 2(3):210-5. DOI:10.5847/wjem.j.1920-8642.2011.03.010
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