Diazoxide Increases Liver and Kidney HSP25 and HSP70 After Shock and Stroke

Joseph C. O'Sullivan, Dadin Fu, Hasan B. Alam, Joseph T. McCabe*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

5 Scopus citations


Background: The compound, diazoxide (DZ), is known to induce preconditioning through its effect as a mitochondrial KATP channel opener and succinate dehydrogenase inhibitor. Our team tested the hypothesis that pharmacological induction of ischemic preconditioning with DZ can offer cytoprotection and preserve vital tissues after hemorrhagic shock and stroke. Materials and methods: Sprague-Dawley male rats received an intraperitoneal injection of sterile saline or 5 mg/kg DZ in saline 24 h prior to 1 h of hemorrhagic shock, by ∼40% total blood loss volume (Shock Study), or a permanent unilateral common carotid ligation just before shock (Stroke + Shock Study). While remaining under isoflurane anesthesia, animals then received 81 mL/kg intravenous sterile saline over the next 45 min for recovery and survived for another 24 h. Results: When DZ was administered 24 h prior to shock, it significantly reduced hyperglycemia, which in vehicle-treated animals persisted after resuscitation. DZ also attenuated hyperlactatemia during the 1-h shock period. With more severe trauma from combined stroke and shock, DZ also decreased hyperlactatemia and hyperglycemia levels but the reduction was only significant for hyperglycemia. The expression levels of heat shock proteins 25 (HSP25) and 70 (HSP70) were used as biomarkers for response of the kidney and liver to DZ and combined stroke and shock. Compared to vehicle-treated animals, DZ-treated rats subjected to shock and stroke exhibited increased HSP25 and HSP70 in kidney and liver tissue. Conclusions: DZ-attenuated physiological indicators of metabolic stress following shock or combined shock and stroke and enhanced the up-regulation of cytoprotective heat shock protein expression.

Original languageEnglish (US)
Pages (from-to)120-130
Number of pages11
JournalJournal of Surgical Research
Issue number1
StatePublished - Sep 2008
Externally publishedYes


  • brain ischemia
  • diazoxide
  • hyperglycaemia
  • lactate
  • mitochondria
  • resuscitation
  • shock
  • stroke

ASJC Scopus subject areas

  • Surgery


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