ABSTRACT: Despite clinical advancement, ischemia-induced myocardial diseases remain an underlying cause of death among individuals throughout the world. Interestingly, we found that the administration of antioxidants can protect cardiomyocytes during ischemia. However, the mechanism involved in inducing the cytoprotective effect under ischemic conditions is not fully elucidated. In this study, we carried out RNA-sequencing data analysis of rat ventricular cardiomyocytes under normoxic, ischemic, and ischemia with eugenol. The RNA sequencing data ascertained that the ischemic condition differentially regulated 7,694 genes in the NRVCs compared to the normoxic condition (padj<0.05). Out of 7,694 genes, 3,774 genes were up-regulated, and 3,920 genes were down-regulated. Also, the administration of eugenol in the presence of ischemic condition up-regulated 159 genes and down-regulated 111 genes. Functional enrichment analysis of differentially regulated genes was carried out using clusterProfiler R and ingenuity pathway analysis. In this study, we found that both the up-regulated and down-regulated genes regulated the post-translational modification of histone proteins during ischemia. Also, the up-regulated genes controlled cell death and survival, protein synthesis and transport etc. The down-regulated genes controlled cellular growth and development, cell signaling, cellular assembly and organization, cellular movement, cellular respiration, and cell death and survival. It was found that eugenol administration under ischemic conditions up-regulated intracellular transduction signaling and down-regulated negative regulation of the metabolic process, negative regulation of nucleic acid templated transcription, and negative regulation of the biosynthetic process. All in all, the administration of antioxidants improves cell survival via down-regulating negative regulation of biosynthetic processes.
