Mitochondrial DNA Oxidative Damage Contributes to Cardiomyocyte Ischemia/Reperfusion‐Injury in Rats: Cardioprotective Role of Lycopene

Mitochondrial (mt) dysfunction and oxidative stress are involved in the pathogenesis of ischemia/reperfusion (I/R)‐injury. Lycopene, a lipophilic antioxidant found mainly in tomatoes and in other vegetables and fruits, can protect mtDNA against oxidative damage. However, the role of mtDNA in myocardial I/R‐injury is unclear. In the present study, we aimed to determine if and how lycopene protects cardiomyocytes from I/R‐injury. In both in vitro and in vivo studies, I/R‐injury increased mt 8‐hydroxyguanine (8‐OHdG) content, decreased mtDNA content and mtDNA transcription levels, and caused mitochondrial dysfunction in cardiomyocytes. These effects of I/R injury on cardiomycoytes were blocked by pre‐treatment with lycopene. MtDNA depletion alone was sufficient to induce cardiomyocyte death. I/R‐injury decreased the protein level of a key activator of mt transcription, mitochondrial transcription factor A (Tfam), which was blocked by lycopene. The protective effect of lycopene on mtDNA was associated with a reduction in mitochondrial ROS production and stabilization of Tfam. In conclusion, lycopene protects cardiomyocytes from the oxidative damage of mtDNA induced by I/R‐injury. J. Cell. Physiol. 230: 2128–2141, 2015. © 2015 Wiley Periodicals, Inc.