Molecular mechanisms of action of styrene toxicity in blood plasma and liver

Styrene is an aromatic colorless hydrocarbon available in liquid form and highly volatile. In its pure form, it gives a sweet smell. The primary source of exposure in the environment is from plastic materials, rubber industries, packaging materials, insulations, and fiber glass and carpet industry. Natural sources of styrene include: few metabolites in plants which are transferred through food chain. The current study was designed to evaluate styrene toxicity, including: superoxide dismutase (SOD) and protein carbonyl, oxidative stress, glucose‐6‐phosphatase (G6Pase), glycogen phosphorylase (GP), and phosphoenolpyruvate carboxykinase (PEPCK) activities, adenosine triphosphate (ATP) to adenosine diphosphate (ADP) ratio, and changes in gene expressions such as glutamate dehydrogenase 1 (GLUD1), glucose transporter 2 (GLUT2), and glucokinase (GCK) in the rat liver tissue. For this purpose, styrene was dissolved in corn oil and was administered via gavage, at doses 250, 500, 1000, 1500, 2000, mg/kg/day per mL and control (corn oil) to each rat with one day off in a week, for 42 days. Plasma SOD and protein carbonyl of plasma were significantly up‐regulated in 1000, 1500, and 2000 mg/kg/day styrene administrated groups (P < .001). In addition, styrene caused an increase in lipid peroxidation (LPO) and reactive oxygen species (ROS) in the dose‐dependent manners in liver tissue (P < .001). Furthermore, the ferrous reducing antioxidant power (FRAP) and total thiol molecules (TTM) in styrene‐treated groups were significantly decreased in liver tissue (P < .001) with increasing doses. In treated rats, styrene significantly increased G6Pase activity (P < .001) and down‐regulated GP activity (P < .001) as compared to the control group. The PEPCK activity was significantly raised in a dose‐dependent manner (P < .001). The ATP/ADP ratio of live cells was significantly raised by increasing the dose (P < .001). There was significantly an up‐regulation of GLUD1 and GCK at 2000 mg/kg group (P < .01) and a down‐regulation for GLUT2 at the same dose. While in the rest of group, GLUT2 showed up‐regulation of relative fold change. By targeting genes such as GLUD1, GLUT2, and GCK, disruption of hepatic gluconeogenesis, glycogenolysis, and insulin secretory functions are obvious. The present study illustrates that induction of oxidative stress followed by changes in G6Pase, GP, and PEPCK activities and the genes responsible for glucose metabolism are the mechanisms of styrene's action in the liver.