Background: Ischemia-reperfusion (I/R) injury causes the dysfunctions of different major organs,
leading to morbidity and mortality on the global scale. Among a battery of therapeutic targets, the heme oxygenase-
1 (HO-1)/carbon monoxide (CO) system has been evaluated for the development of new therapies against
I/R injury. The enzyme HO-1 catalyzes the degradation of heme into three biologically active end products,
namely biliverdin/bilirubin, CO and ferrous ion. Interestingly, CO is one of a few bioactive gaseous molecules
with the capability of regulating inflammation, cell survival and growth. In fact, several CO-releasing compounds
have been developed for directly reprogramming the intracellular apoptotic, inflammatory and proliferative signaling
networks. In parallel, chemical and genetic approaches have also been evaluated for up-regulating HO-1
expression as an endogenous mechanism to ameliorate I/R injury and heal wounds.
Methods: In this review, we discussed the recent studies on the therapeutic potential of HO-1/CO system in the
treatment of I/R injury in the heart, brain, liver, kidney, lung, intestine and retina. We focused on the activities
and underlying mechanisms of various therapeutic strategies to regulate HO-1/CO system against I/R injury.
Results: A large number of studies have demonstrated that HO-1/CO system exhibits potent anti-oxidative, antiapoptotic,
anti-inflammatory and cytoprotective activities against I/R injury. The regulation of HO-1/CO expression
has been achieved either by genetic overexpression of HO-1 cDNA or pharmacological induction with drugs
including curcumin and resveratrol.
Conclusion: The HO-1/CO system is a potential target for treating I/R injury. Further studies should be directed
to in vivo efficacy and clinical application of HO-1/CO system in the therapy of I/R injury.