Effect of styrene exposure on plasma parameters, molecular mechanisms and gene expression in rat model islet cells

- Styrene causes increased plasma insulin, glucose tolerance and insulin resistance.
- Styrene induces oxidative stress and inflammatory cytokines in plasma.
- Styrene up-regulates the activities of caspase-3 and −9 in Langerhans islets.
- Styrene disrupts insulin secretion by targeting islets GLUD1, GLUT2 and GCK.

Styrene is an aromatic hydrocarbon compound present in the environment and have primary exposure through plastic industry. The current study was designed to evaluate styrene-induced toxicity parameters in rat plasma fasting blood glucose (FBG) level, oral glucose tolerance, insulin secretion, oxidative stress, and inflammatory cytokines in cellular and molecular levels. Styrene was dissolved in corn oil and administered at different doses (250, 500, 1000, 1500, 2000 mg/kg/day and control) to each rat, for 42 days. In treated groups, styrene significantly increased fasting blood glucose, plasma insulin (p < 0.001) and glucose tolerance. Glucose tolerance, insulin resistance and hyperglycemia were found to be the main consequences correlating gene expression of islet cells. Styrene caused a significant enhancement of oxidative stress markers (p < 0.001) and inflammatory cytokines in a dose and concentration-dependent manner in plasma (p < 0.001). Moreover, the activities of caspase-3 and −9 of the islet cells were significantly up-regulated by this compound at 1500 and 2000 mg/kg/day styrene administrated groups (p < 0.001). The relative fold change of GLUD1 was downregulated (p < 0.05) and upregulated at 1500 and 2000 mg/kg, respectively (p < 0.01). The relative fold changes of GLUT2 were down regulated at 250 and 1000 mg/kg and up regulated in 500, 1500 and 2000 mg/kg doses of styrene (p < 0.01). The expression level of GCK indicated a significant upregulation at 250 mg/kg and downregulation of relative fold changes in the remaining doses of styrene, except for no change at 2000 mg/kg of styrene for GCK. Targeting genes (GLUD1, GLUT2 and GCK) of the pancreatic islet cells in styrene exposed groups, disrupted gluconeogenesis, glycogenolysis pathways and insulin secretory functions. The present study illustrated that fasting blood glucose, insulin pathway, oxidative balance, inflammatory cytokines, cell viability and responsible genes of glucose metabolism are susceptible to styrene, which consequently lead to other abnormalities in various organs.