Acute hyperglycemia worsens hepatic ischemia/reperfusion injury in rats.
OBJECTIVE
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.


METHODS
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.


RESULTS
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).


CONCLUSIONS
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.
Behrends
Matthias
M
Department of Anesthesia and Perioperative Care, University of California San Francisco, San Francisco, CA 94143-0648, USA. behrendsm@anesthesia.ucsf.edu
Martinez-Palli
Graciela
G
Niemann
Claus U
CU
Cohen
Sara
S
Ramachandran
Rageshree
R
Hirose
Ryutaro
R
D000208:Acute Disease; D000410:Alanine Transaminase / Q000378:metabolism; D000818:Animals; D001707:Biopsy, Needle; D001786:Blood Glucose / Q000378:metabolism*; D004195:Disease Models, Animal; D018450:Disease Progression; D006360:Heat-Shock Proteins / Q000378:metabolism; D006943:Hyperglycemia / Q000150:complications*; D007150:Immunohistochemistry; D008107:Liver Diseases / Q000150:complications* / Q000401:mortality / Q000473:pathology*; D008111:Liver Function Tests; D008297:Male; D020556:Neutrophil Infiltration; D018384:Oxidative Stress / Q000502:physiology; D011336:Probability; D011897:Random Allocation; D051381:Rats; D011917:Rats, Inbred Lew; D015427:Reperfusion Injury / Q000150:complications* / Q000401:mortality / Q000473:pathology*; D015996:Survival Rate
D001786:Blood Glucose; D006360:Heat-Shock Proteins; D000410:Alanine Transaminase