Strategies for treating
myocardial ischemia in the clinic usually include re-canalization of the coronary arteries to restore blood supply to the myocardium. However, myocardial reperfusion insult often leads to oxidative stress and
inflammation, which in turn leads to apoptosis and
necrosis of myocardial cells, for which there are no standard treatment methods. The aim of this study was to determine the pharmacological effect of
indole-3-carbinol (I3C), a
phytochemical found in most cruciferous vegetables, in a mouse model of
myocardial ischemia/
reperfusion injury (MIRI). Our results showed that I3C pretreatment (100 mg/kg, once daily, i. p.) prevented the MIRI-induced increase in
infarct size and serum
creatine kinase (CK) and
lactate dehydrogenase (LDH) in mice. I3C pretreatment also suppressed cardiac apoptosis in MIRI mice by increasing the expression levels of the
anti-apoptotic protein Bcl-2 and decreasing the expression levels of several apoptotic
proteins, including Bax,
caspase-3, and
caspase-9. In addition, I3C pretreatment was found to reduce the levels of parameters reflecting oxidative stress, such as
dihydroethidium (DHE),
malondialdehyde (MDA),
reactive oxygen species (ROS), and
nitric oxide (NO), while increasing the levels of parameters reflecting anti-oxidation, such as total
antioxidant capacity (T-AOC) and
glutathione (GSH), in MIRI-induced ischemic heart tissue. I3C pretreatment was also able to remarkably decrease the expression of
tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and
interleukin-6 (IL-6)
mRNA in ischemic heart tissue. These results demonstrate that administration of I3C protects the heart from MIRI through its anti-apoptotic,
antioxidant, and anti-inflammatory effects.