Role of bisphenol A as environmental factor in the promotion of non-alcoholic fatty liver disease: in vitro and clinical study.

Background: Bisphenol A is an endocrine disrupting chemical associated with type 2 diabetes mellitus (T2DM), cardiovascular disease and liver enzyme abnormalities.

Aim: To evaluate bisphenol A plasma and urine levels in non-alcoholic fatty liver disease (NAFLD) patients compared to healthy subjects. Furthermore, we evaluated, in human HepG2 cells, the effects of exposure to different concentrations of bisphenol A on both oxidative stress induction and cell proliferation.

Methods: We enrolled 60 patients with histological diagnosis of NAFLD with or without T2DM and sixty healthy subjects. In vitro, the proliferation of bisphenol A-exposed HepG2 cells at two different concentrations (0.025 and 0.05 μM) was evaluated, both at high (H-HepG2) and at low (L-HepG2) glucose concentrations for 48 h. Lipoperoxidation was assessed by thiobarbituric acid reactive substances (TBARS) assay.

Results: Bisphenol A levels were significantly higher in 60 NAFLD subjects, both in urine and in plasma (P < 0.0001) when compared to controls and, in this group, it appeared to be higher in 30 non-alcoholic steatohepatitis patients compared to 30 simple steatosis subjects (P < 0.05), independently from the presence of T2DM. After a bisphenol A-free diet for 1 month, NAFLD patients showed a significant reduction in bisphenol A circulating levels (P < 0.05), without a significant reduction in urine levels. H-HepG2 cells treated with bisphenol A (0.05 μM) increased proliferation compared to controls at 48 h (P < 0.0001). Bisphenol A increased TBARS levels at 48 h versus controls.

Conclusions: Our study reveals a possible role of bisphenol A as an environmental factor involved in the promotion of NAFLD, particularly in T2DM patients.