Effects of Pyrene on Human Liver HepG2 Cells: Cytotoxicity, Oxidative Stress, and Transcriptomic Changes in Xenobiotic Metabolizing Enzymes and Inflammatory Markers with Protection Trial Using Lycopene

Abstract

Pyrene is one of the major polycyclic aromatic hydrocarbons formed during heat treatment of meat and in car exhausts; however, few studies have investigated pyrene-induced adverse effects on human cell lines. This study aimed at the investigation of pyrene-induced cytotoxicity and oxidative damage in human liver HepG2 cells at environmentally relevant concentrations. Pyrene-induced changes in mRNA expression of xenobiotic metabolizing enzymes (XMEs), xenobiotic transporters, antioxidant enzymes, and inflammatory markers were investigated using real-time PCR. As a protection trial, the ameliorative effects of lycopene, a carotenoid abundantly found in tomato, were investigated. The possible mechanisms behind such effects were examined via studying the co exposure effects of pyrene and lycopene on regulatory elements including the aryl hydrocarbon receptor (Air) and elytroid 2-related factor 2 (RF). The achieved results indicated that pyrene caused significant cytotoxicity at 50 n, with a clear production of reactive oxygen species (ROS) in a dose-dependent manner. Pyrene upregulated mRNA expression of phase I enzymes including CYP1A1, 1A2, and CYP1B1 and inflammatory markers including TNFα and Cox2. However, pyrene significantly downregulated phase II enzymes, xenobiotic transporters, and antioxidant enzymes. Interestingly, lycopene significantly reduced pyrene-induced cytotoxicity and ROS production. Moreover, lycopene upregulated detoxification and antioxidant enzymes, probably via its regulatory effects on Air- and RF-dependent pathways.