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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.

Misuse of the psychostimulant methamphetamine (METH) could induce serious hepatotoxicity. Our previous study revealed the effects of luteolin on alleviating METH-induced hepatotoxicity, however, the detailed mechanisms have not been elucidated. In this study, rats were orally pretreated with 100 mg/kg luteolin or sodium dodecyl sulfate water, and then METH (15 mg/kg, intraperitoneal [i.p.]) or saline was administered. Histopathological and biochemical analyses were used to determine the alleviative effects of luteolin. Based on the RNA-sequencing data, METH induced 1859 differentially expressed genes (DEGs) in comparison with the control group, which were enriched into 11 signaling pathways. Among these DEGs, 497 DEGs could be regulated through luteolin treatment and enriched into 16 pathways. The p53 signaling pathway was enriched in both METH administered and luteolin pretreated rats. Meanwhile, luteolin significantly suppressed METH-induced elevation of p53, caspase9, caspase3, cleaved caspase3, the ratio of Bax/Beclin-2, as well as autophagy-related Beclin-1, Atg5, and LC3-II. Luteolin also relieved METH-induced hepatotoxicity by decreasing inflammation factors, including TNF-α, IL-1β, and IL-18. Moreover, the levels of PI3K, p-Akt, and the normalized ratio of p-Akt/Akt declined after METH administration, whereas luteolin pretreatment failed to reverse these effects. Our results suggest that luteolin alleviates METH-induced hepatic apoptosis, autophagy, and inflammation through repressing the p53 pathway. It further illustrates the protective mechanisms of luteolin on METH-induced hepatotoxicity and provides a research basis for clinical treatment.

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Detection of the vitality of wounds is one of the most important issues in forensic practice. This study investigated mRNA and protein levels of CXCL1 and CXCR2 in skin wounds in mice and humans. Western blot analysis of CXCL1 and CXCR2 protein levels showed no difference between wounded and intact skin. However, mRNA levels demonstrated higher expression of CXCL1 and CXCR2 in contused mouse and human skin, compared with intact skin. At postmortem there were no remarkable changes in CXCL1 and CXCR2 mRNA levels in contused mouse skin. Increased mRNA expression was observed in contused mouse skin up to 96 h and 72 h after death for CXCL1 and CXCR2 respectively. In human samples of wounded skin, increased CXCL1 mRNA levels were detected up to 48 h after autopsy in all 5 cases, while increased CXCR2 mRNA levels were observed 48 h after autopsy in 4 of 5 cases. These findings suggest that the levels of CXCL1 and CXCR2 mRNA present in contused skin can be used as potential markers for a vital reaction in forensic practice.