Pharmacological modulation of
heme oxygenase (HO) gene expression may have significant therapeutic potential in
oxidant-induced disorders, such as
ischemia reperfusion (I/R) injury.
Higenamine is known to reduce ischemic damages by unknown mechanism(s). The protective effect of
higenamine on myocardial I/R-induced injury was investigated.
Ligation of rat left anterior descending coronary artery for 30 min under
anesthesia was done and followed by 24 h reperfusion before sacrifice. I/R-induced myocardial damages were associated with mitochondria-dependent apoptosis as evidenced by the increase of
cytochrome c release and
caspase-3 activity. Administration of
higenamine (bolus, i.p) 1 h prior to I/R-injury significantly decreased the release of
cytochrome c,
caspase-3 activity, and Bax expression but up-regulated the expression of Bcl-2, HO-1, and HO
enzyme activity in the left ventricles, which were inhibited by
ZnPP IX, an
enzyme inhibitor of HO-1. In addition,
DNA-strand break-, immunohistochemical-analysis, and TUNEL staining also supported the anti-apoptotic effect of
higenamine in I/R-injury. Most importantly, administration of
ZnPP IX inhibited the beneficial effect of
higenamine. Taken together, it is concluded that HO-1 plays a core role for the protective action of
higenamine in I/R-induced myocardial injury.