Oral bimoclomol elevates heat shock protein 70 and reduces myocardial infarct size in rats.
Bimoclomol has been shown to increase an inducible member of the heat shock protein 70 family (HSP70) and cytoprotect in vitro. Here, we addressed whether oral pretreatment of rats with bimoclomol could elevate myocardial HSP70 and reduce infarct size in a rat model of ischemia and reperfusion. Rats were pretreated with bimoclomol at 3, 6 or 18 h or with 42 degrees thermal stress 24 h before ischemia. Infarct size was significantly decreased 6 h after oral administration of bimoclomol and 24 h after thermal stress. Left ventricles from a separate group of rats were examined for HSP70 levels. Western blots showed a significant increase in HSP70 6 h after oral administration of bimoclomol and 24 h after thermal stress. There was a significant correlation (P<0.05) between HSP70 induction and infarct size reduction, whether produced by thermal stress or oral administration of bimoclomol. Thus, bimoclomol can increase HSP70 and reduce infarct size in a rat model of ischemia and reperfusion.
Lubbers
Nathan L
NL
Department of Integrative Pharmacology, Abbott Laboratories, 100 Abbott Park Road, Abbott Park, IL 60064-6119, USA. nathan.lubbers@abbott.com
Polakowski
James S
JS
Wegner
Craig D
CD
Burke
Sandra E
SE
Diaz
Gilbert J
GJ
Daniell
Katina M
KM
Cox
Bryan F
BF
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D004195:Disease Models, Animal; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism*; D006339:Heart Rate / Q000187:drug effects; D007094:Imides / Q000627:therapeutic use*; D009203:Myocardial Infarction / Q000503:physiopathology / Q000517:prevention & control*; D009206:Myocardium / Q000378:metabolism*; D020011:Protective Agents / Q000627:therapeutic use*; D011725:Pyridines / Q000627:therapeutic use*; D051381:Rats
D018840:HSP70 Heat-Shock Proteins; D007094:Imides; D020011:Protective Agents; D011725:Pyridines; C108730:bimoclomol