Ranolazine exhibits anti-inflammatory and antioxidant activities in H9c2 cardiomyocytes

Abstract

OBJECTIVE: The aim of this study was to evaluate the effectiveness of ranola-zine on hypoxia-inducible factor-1 alpha (HIF-1 alpha) and oxidative stress in H9c2 cardiomyocyte cells.MATERIALS AND METHODS: We have as-sessed the effects of increasing concentrations of methotrexate (MTX) and ranolazine on prolif-eration of H9c2 rat cardiomyocyte cells by MTT assay. Malondialdehyde (MDA) protein oxidation [advanced oxidation protein products (AOPPs)], lipid hydroperoxide (LOOH) and xanthine oxidase (XO) activity as oxidative stress markers and HIF-1 alpha levels increased and total thiol (T-SH), cata-lase (CAT) activity and total antioxidant capacity (TAC) antioxidant capacity markers decreased in MTX-treated cells compared to control cells.RESULTS: Oxidative stress markers decreased, and antioxidant capacity markers increased in cells treated with ranolazine alone compared to control cells. For all parameters, we showed that the levels of oxidant, antioxidant markers and HIF-1 alpha in cells treated with MTX and ranolazine together reached the level of the control group, and ranolazine re-versed the oxidative damage caused by MTX.CONCLUSIONS: The cell viability increased the levels of oxidant and prooxidant markers and decreased the levels of antioxidant markers de-creased in H9c2 cardiomyocytes induced by oxi-dative stress. These results suggest that ranola-zine may protect the cardiomyocytes from MTX-in-duced oxidative damage. The effects of ranolazine could result from its antioxidant properties.