Differences in microRNA expression in rat liver following single- and combined administration of caffeine and dextromethorphan

Abstract

In forensic practice, blood drug levels are important determinants in the diagnosis of deaths related to drug poisoning. Even at non-lethal concentrations, potential drug interactions must be considered when multiple drugs are detected. MicroRNAs (miRNAs) have attracted increasing attention owing to their short length, robustness, and resistance to postmortem changes. Caffeine and dextromethorphan are among the most commonly abused substances by young people in Japan. However, reports on interactions between caffeine and dextromethorphan and comprehensive miRNA analyses following the administration of these drugs are limited. We aimed to determine whether miRNA expression differs in rats administered caffeine and dextromethorphan alone or in combination. We performed a comprehensive analysis of miRNAs in the livers of rats treated with caffeine, dextromethorphan, or both drugs. Eight miRNAs showed changes in expression exclusively in the combination treatment group, with five upregulated and three downregulated. Among these, rno-miR-34a-5p expression was significantly decreased in the combination group, as confirmed by quantitative RT-PCR. Although no differences were observed between groups in behavioral and pathological assessments at the administered doses, distinct changes in miRNA expression were detected. These results suggest that miRNAs may serve as biomarkers to indicate pathological differences between single and combined drug administration.