RNA-sequencing analysis of the effect of luteolin on methamphetamine-induced hepatotoxicity in rats: a preliminary study

PeerJ. 2020 Feb 6:8:e8529. doi: 10.7717/peerj.8529. eCollection 2020.

Abstract

In this study, RNA-sequencing (RNA-seq) was utilized to investigate the effects of luteolin on hepatotoxicity caused by methamphetamine (METH). The rats in METH group were administrated with METH (15 mg/kg, two times per day) via intraperitoneal (i.p.) injections for four consecutive days. The rats in luteolin + METH group were firstly administrated with luteolin (100 mg/kg, once a day) by oral gavage for 3 days before METH treatment. Lueolin attenuated the hepatotoxicity induced by METH via histopathological and biochemical analysis. The results of RNA-seq showed that luteolin could regulate 497 differentially expressed genes (DEGs), and the selected DEGs were mainly enriched in eight pathways, according to KEGG analysis. Furthermore, qRT-PCR was utilized to verify the results of RNA-seq. Six genes were selected as follows: liver enriched antimicrobial peptide 2 (Leap2), fatty acid synthase (Fasn), fatty acid binding protein 5 (Fabp5), patatin like phospholipase domain containing 3 (Pnpla3), myelin basic protein (Mbp) and calmodulin 3 (Calm3). Though because of the design flaws, the luteolin group has not been included, this study demonstrated that luteolin might exert hepato-protective effects from METH via modulation of oxidative phosphorylation, cytochrome P450 and certain signaling pathways.

Keywords: Differentially expressed genes (DEGs); Hepatotoxicity; Luteolin; Methamphetamine; RNA-seq; qRT-PCR.

Grants and funding

This research work was supported by the National Natural Science Foundation of China (Grant No. 81430045 and 81871528 to Huijun Wang and Grant No. 81871526 to Qi Wang). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.