Hyperglycemia in streptozotocin-induced diabetic rat increases infarct size associated with low levels of myocardial HO-1 during ischemia/reperfusion.
This study investigated the role of heme oxygenase (HO)-1 in the cardiac tissue injury of acute ischemia/reperfusion (I/R) in diabetic streptozotocin (STZ)-induced hyperglycemic rats. The effects of 1) hemin, an inducer of HO expression and activity, and 2) zinc protoporphyrin IX (ZnPP-IX), an inhibitor of HO activity, have also been investigated on the tissue injury by I/R and some mediators released in these circumstances. STZ hyperglycemic rats had impaired levels of HO-1 within the cardiac tissue and increased myocardial infarct size (IS) following I/R, as compared with the nondiabetic rats. In these rats, administration of hemin 4 mg/kg 18 h before I/R increases the levels of HO-1 within the tissue. However, the values of HO-1 assayed in these circumstances were significantly lower (P < 0.01) than those assayed in nondiabetic animals subjected to the same procedures; IS was much more extended (P < 0.01) than in the parent nondiabetic group. STZ hyperglycemic rats also predisposed the heart to produce high levels of the cytokines interleukin (IL)-1beta and CXCL8. Subsequent I/R further increased (P < 0.01) the cytokine production, an effect partly prevented by hemin treatment. This recovered the huge number of infiltrated polymorphonuclear (PMN) leukocytes within the cardiac tissue associated with the STZ hyperglycemic state and I/R damage.
Di Filippo
Clara
C
Department of Experimental Medicine, Section of Pharmacology L. Donatelli, Second University of Naples, Italy.
Marfella
Raffaele
R
Cuzzocrea
Salvatore
S
Piegari
Elena
E
Petronella
Pasquale
P
Giugliano
Dario
D
Rossi
Francesco
F
D'Amico
Michele
M
D000818:Animals; D039481:CD11b Antigen / Q000502:physiology; D003921:Diabetes Mellitus, Experimental / Q000097:blood / Q000201:enzymology / Q000503:physiopathology*; D015870:Gene Expression; D006360:Heat-Shock Proteins / Q000378:metabolism / Q000502:physiology*; D006419:Heme Oxygenase (Decyclizing); D006427:Hemin / Q000502:physiology; D006943:Hyperglycemia / Q000201:enzymology / Q000473:pathology / Q000503:physiopathology*; D007963:Leukocytes, Mononuclear; D008297:Male; D009203:Myocardial Infarction / Q000097:blood / Q000201:enzymology / Q000473:pathology*; D015428:Myocardial Reperfusion Injury / Q000097:blood / Q000201:enzymology / Q000473:pathology*; D009206:Myocardium / Q000201:enzymology* / Q000473:pathology; D010105:Oxygenases / Q000378:metabolism / Q000502:physiology*; D011524:Protoporphyrins / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley
D039481:CD11b Antigen; D006360:Heat-Shock Proteins; D011524:Protoporphyrins; C017803:zinc protoporphyrin; D006427:Hemin; D010105:Oxygenases; D006419:Heme Oxygenase (Decyclizing); C491523:Hmox1 protein, rat