Transcriptomics and metabolomics reveal the alleviating effect of lycopene on di-(2-ethylhexyl) phthalate-induced...

Di(2-ethylhexyl) phthalate (DEHP), a prevalent plasticizer in medical, personal care, and food packaging items, leads to extensive human exposure and liver accumulation, resulting in notable liver toxicity. Lycopene (Lyc), a strong antioxidant in red fruits and vegetables, protects the liver by reducing oxidation, inflammation, and cell death. However, the exact ways DEHP causes liver damage and how Lyc counteracts it are not well understood. In this study, integrated metabolomics and transcriptomics were employed to investigate the protective mechanisms of Lyc in mice administered DEHP (200 mg/kg) and Lyc (5 mg/kg) via gavage. The findings indicated that DEHP caused hepatocytes to have shrunken nuclei and looser cytoplasm, impaired liver function, increased oxidative stress indicators, and reduced antioxidant activity markers. DEHP altered hepatic metabolite profiles, notably reducing the levels of isodeoxycholic acid, 3beta,7alpha-dihydroxychol-5-en-24-oic acid, lithocholic acid glucuronide, 3-dehydrocholic acid, and cholic acid. Remarkably, the occurrence of these disorders and injuries was prevented by Lyc treatment. Mechanistically, Lyc was found to alleviate the DEHP-induced suppression of the PI3K-AKT signaling pathway and activation of the p53 signaling pathway. This investigation reveals that the alleviation of DEHP-induced hepatotoxicity by Lyc is closely associated with modulations in the liver metabolome and transcriptome.