Lycopene Protects Against Hypoxia/Reoxgenation-injury In Neonatal Mouse Cardiomyocytes And It’s Mechnism

Background: Ischemia/reperfusion-injury is a worldwide problem thatpeople are constantly looking for a new intrinsic or exogenous method toreduce this damage. Ischemia/reperfusion-induced apoptosis ofcardiomyocytes plays an important role in Ischemia/reperfusion-injury.Lycopene is an antioxidant carotenoid that has been shown to have protectiveproperties on cardiovascular system. However, whether Lycopene can protectthe cardiomyocytes from Ischemia/repurfusion -injury and the possiblemechanism is not clear.Objective: The purpose of this study was to investigate whetherLycopene could efficiently protect against Ischemia/reperfusion-injury, andthe possible mechanism.Methods: Cardiomyocytes were isolated from neonatal C57BL/6 mouse.After cultured for 48-72 h, cardiomyocytes were exposed to different hypoxiatime to search for a proper hypoxia time, then cardiomyocytes were exposedto different reoxgenation time to find out a suitable reoxgenation time.Cardiomyocytes were underwent hypoxia/ reoxgenation treatment tosimulated Ischemia/reperfusion-injury. To investigate the possiblecardiomyocytes protective effects of Lycopene on Ischemia/reperfusion-injury,cardiomyocytes were divided into four groups: control; Lycopene group, inwhich the the cardiomyocytes were pretreatment with 0.5μM Lycopene for 4h but not followed by H/R treatment; H/R group, in which the cardiomyocyteswere underwent H/R treatment but without Lycopene pretreatment; and H/R +Lycopene group, in which the cardiomyocytes were pretreatment with 0.5μM Lycopene for 4 h before H/R treatment. Then, the apoptosis index ofcardiomyocytes, intracellular ROS and MDA levels, the opening of mPTP, thefunction of mitochondria, the release of cytochromec from mitochondrialmatrix into the cytosol and the activity of caspse3 were determined in thesegroups.Results: The apoptosis index in the H/R group significantly increasedcompared to control and Lycopene groups (P<0.05). while, the apoptosisindex in the H/R+Lycopene group was smaller than the H/R group(P<0.05);The intracellular ROS level in the H/R group significantly increasedcompared to control and Lycopene groups (P<0.01) and the intracellularMDA level in the H/R group significantly increased compared to control andLycopene groups (P<0.05). while, the intracellular ROS and MDA level in theH/R+Lycopene group was decreased compared with the H/R group; TheNRFU in the H/R group significantly decreased compared to control andLycopene groups (P<0.01). while, the NRFU in the H/R+Lycopene group wasincreased compared with the H/R group; TheΔΨm in the H/R groupsignificantly decreased compared to control and Lycopene groups (P<0.01)and the intracellular ATP level in the H/R group significantly decreasedcompared to control and Lycopene groups (P<0.05). while, theΔΨm and theintracellular ATP level in the H/R+Lycopene group was increased comparedwith the H/R group; the release of cytochromec from mitochondrial matrixinto the cytosol and the activity of caspse3 were also significantly increased inH/R group compare to control (P<0.05). However, the release ofcytochromec from mitochondrial matrix into the cytosol was reduced inH/R+Lycopene group and the activity of caspse3 were efficiently attenuated in H/R+Lycopene group compared with the H/R group (P<0.05).Conclusions: These results demonstrated that Lycopene protect againstIschemia/repurfusion-injury in vitro, which may be attributable to its roles inimproving mitochondrial function.