Nociceptin/orphanin FQ opioid receptor selective ligand MCOPPB as a potent senolytic drug

Here we used RNA-Seq to gain deep mechanistic insight into the effects of the drug MCOPPB on C57BL6J mice that were fed with chow diet or that received a low dose of a carcinogen (25 mg/kg diethynitrosamine, DEN) and then fed with high fat diet (HFD). Only in a second step we decided to focus exclusevely on the groups under chow diet. Heatmap analysis of the differentially expressed genes between the two groups revealed a difference in transcriptomic profile of MCOPPB-treated mice compared to the control condition. Genes were considered differentially expressed between groups if their expression values significantly differed by >4 fold. Statistical differences in gene expression were assessed by the ANOVA test. Correction for multiple test was achieved by the Benjamini-Hochberg procedure. The significance threshold was set to 0.05. Significantly enriched transcripts over-represented in MCOPPB compared to control were implicated in a number of functions and diseases. Specifically,Ingenuity pathway analysis (IPA) identified differences in hepatic fibrosis, oxidative stress,Ephrin A signaling, GP6 signaling pathway, Ephrin B signaling and others categories between MCOPPB versus CTL. These data suggested a slight pro-fibrotic effect in the liver of MCOPPB. Overall design: Profiling the transcriptome of C57BL6J mice under chow diet or high fat diet+DEN and treated with MCOPPB, using RNA-Seq.