A multifactorial study of in situ antioxidant activity of modified GrO in myocardial reperfusion injury using the Langerdorff model.

Carbon nanomaterials possess antioxidant properties that can be applied in biomedicine and clinics for the development of new highly effective treatments against oxidative stress-induced diseases like ischemic heart disease. We previously reported the usage of graphene oxide (GrO) as a precursor for the elaboration of such prototypes. The promising findings led to the development of two new modifications of GrO: nitrogen-doped (N-GrO) and l-cysteine functionalized (S-GrO) derivatives as possible antioxidant agents in ischemia-reperfusion (I/R) conditions. In this study, the cardioprotective and antioxidant potential of modified GrO as a pre-treatment in rats was evaluated for the first time. In Langendorff isolated rat heart I/R model, the left ventricle developed pressure (LVDP), the end-diastolic pressure (EDP), the maximal (dP/dtmax) and minimal (dP/dtmin) value of the first derivative of LVDP, and heart rate (HR) were measured. The oxidative-nitrosative markers, in particular, the rate of O2*- and H2O2 generation, the content of malonic dialdehyde, diene conjugates, and leukotriene as well as cNOS and iNOS activity were estimated. Obtained results show a significant restoration of cadiodynamic parameters at the reperfusion period. Simultaneously, all samples significantly reduced the rate of reactive oxygen species (ROS) and lipid peroxidation markers in cardiac homogenates and preserved cNOS activity at the preischemic level. This evidence makes GrO derivatives promising candidates for the correction of reperfusion disorders affecting myocardial function.

Graphene oxide nanoflakes prevent reperfusion injury of Langendorff isolated rat heart providing antioxidative activity in situ.

Carbon materials possess powerful antioxidant activity that might be promising for the development of new generation treatment of cardiovascular diseases, ischemic conditions, and reperfusion injury. The present study aimed to characterize the structure of nanosized graphene oxide (GrO) sample and evaluate the antioxidant efficacy of GrO in situ models of oxidative stress widely used in pre-clinical studies. The structure and surface chemistry of the initial samples were analyzed via LDS, RAMAN, LDI, TPD-MS, and FTIR methods. The GrO showed a strong ability to scavenge DPPH, hydroxyl, and superoxide anion free radicals and have a total antioxidant capacity. The DFT quantum-chemical calculation demonstrated the radical scavenging effect of GrO proceeding due to the physical adsorption of the free radical on the surface. For evaluation of the antioxidant effect of GrO in situ, we used the model of ischemia-reperfusion (I/R) of Langendorff isolated rat heart. We revealed that intravenous pretreatment of Wistar male rats with GrO significantly increased resistance of myocardium to I/R, improved restoration of heart function, prevented non-effective oxygen utilization, and I/R-induced reactive oxygen species production in cardiac tissue. Thus, our data demonstrate the perspective of further use of GrO for the development of antiischemic therapy.