Therapeutic Potential of Heme Oxygenase-1/carbon Monoxide System Against Ischemia-Reperfusion Injury

Author(s): Yuanyuan Cheng, Jianhui Rong*.

Journal Name: Current Pharmaceutical Design

Volume 23 , Issue 26 , 2017

Abstract:

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.

Keywords: Ischemia-reperfusion injury, hemo oxygenase-1/carbon monoxide, anti-oxidative, anti-apoptotic, anti-inflammatory, pharmacological induction.

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Article Details

VOLUME: 23
ISSUE: 26
Year: 2017
Page: [3884 - 3898]
Pages: 15
DOI: 10.2174/1381612823666170413122439
Price: $58

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