We investigated the cardioprotective efficacy of a new compound, 3-[(1H-1-indolyl)methyl] -4-amino 4,5-dihydro-1H,1,2,4 triazole-5-thione (
C6458). The effect of
C6458 on the reduction of the
infarct size and its protective ability against oxidative damage of the myocardium after
ischemia-reperfusion was examined in rabbits that were subjected to 30 min regional
ischemia and 2 h reperfusion.
C6458 was administered by continuous infusion for 30 min starting at the 10th minute of sustained
ischemia and ending at the 10th minute of reperfusion (two doses, 100 and 200 micromol/kg BW).
Infarct and risk areas were delineated with Zn2+-Cd2+ particles and triphenyl tetrazolium
chloride staining.
Antioxidant activity was detected spectrophotometrically by the measurement of
malondialdehyde formation.
C6458 reduced significantly the level of
malondialdehyde in rabbits under
ischemia-reperfusion at both doses. Interestingly, at the dose of 200 micromol/kg, the compound decreased the
malondialdehyde levels from the 1st minute of reperfusion and significantly reduced
infarct size. The
free radical scavenging properties of the compound were examined in vitro by determination of the interaction with the
1,1-diphenyl-2-picrylhydrazyl (DPPH) stable
free radical. The ability of the
C6458 to scavenge HO* was established by its competition with
dimethyl sulfoxide (
DMSO) for HO radicals. The compound tested showed a significant effect in the above assays. We conclude that
C6458 possesses a protective effect against both damaged myocardium and
infarct size in anesthetized rabbits. This beneficial effect may be attributed, at least in part, to its
antioxidant and
free radical scavenging activity.