Vitamin E (α-Tocopherol) Does Not Ameliorate the Toxic Effect of Bisphenol S on the Metabolic Analytes and Pancreas Histoarchitecture of Diabetic Rats

Abstract

This study investigated whether the coadministration of vitamin E (VitE) diminishes the harmful effects provoked by plasticizer bisphenol S (BPS) in the serum metabolites related to hepatic and renal metabolism, as well as the endocrine pancreatic function in diabetic male Wistar rats. Rats were divided into five groups (n = 5-6); the first group was healthy rats (Ctrl group). The other four groups were diabetic rats induced with 45 mg/kg bw of streptozotocin: Ctrl-D (diabetic control); VitE-D (100 mg/kg bw/d of VitE); BPS-D (100 mg/kg bw/d of BPS); The animals from the VitE + BPS-D group were administered 100 mg/kg bw/d of VitE + 100 mg/kg bw/d of BPS. All compounds were administered orally for 30 days. Body weight, biochemical assays, urinalysis, glucose tolerance test, pancreas histopathology, proximate chemical analysis in feces, and the activity of antioxidants in rat serum were assessed. The coadministration of VitE + BPS produced weight losses, increases in 14 serum analytes, and degeneration in the pancreas. Therefore, the VitE + BPS coadministration did not have a protective effect versus the harmful impact of BPS or the diabetic metabolic state; on the contrary, it partially aggravated the damage produced by the BPS. VitE is likely to have an additive effect on the toxicity of BPS.

Keywords: biochemistry; bisphenol S; diabetic rats; endocrine-disrupting compounds; vitamin E.

Figure 1

Experimental design.

Figure 2

Effects of vitamin E (VitE), bisphenol S (BPS), or VitE + BPS on body weight (BW). BW was measured weekly and on day 30 of oral treatment; (a) Mean body weight. (b) The percentage of control weight. (c) The total weight (mean of all weights evaluated at 7, 14, 21, and 28 days). Data are expressed as mean ± SEM (n = 5/6 animals per group) of male-treated Wistar rats. * p ≤ 0.05 versus Ctrl group; ^# p ≤ 0.05 versus Ctrl-D group; ^$ p ≤ 0.05 versus BPS-D group, ^& p ≤ 0.05 versus VitE-D (specific p values are included in the text).

Figure 3

Effects of Vitamin E (VitE), bisphenol S (BPS), or VitE + BPS on (a) glutathione peroxidase (GPx), (b) glutathione reductase (GR), and (c) glutathione-S-transferase (GST) activity in serum of treated male Wistar rats. Data are presented as mean ± SEM, n = 5–6 animals per group. * p ≤ 0.05 versus Ctrl group (specific p values are included in the text).

Figure 4

(a) Blood glucose concentrations (mg/dL) following administration of glucose load (2 g/kg bw) in male Wistar rats. (b) Mean total glucose area under the curve (AUC). Data are presented as mean ± SEM, n = 5–6 animals per group. * p ≤ 0.05, compared to the Ctrl group; ^# p ≤ 0.05, compared to the Ctrl-D group (specific p values are included in the text).

Figure 5

Effects of Vitamin E (VitE), bisphenol S (BPS), VitE + BPS on (a) blood urea nitrogen (BUN; reference value (RV): 4.02–9.13 mmol/L); (b) total cholesterol (RV: 0.51–2.85 mmol/L); (c) alanine aminotransferase (ALT; RV: 19–48 U/L); (d) albumin (RV: 30–50 g/L); (e) globulin (RV: 15–25 g/L); (f) total protein (RV: 56–76 g/L); (g) urea (RV: 4.28–8.57 mmol/L); (h) total bilirubin (RV: 0.86–2.57 μmol/L). Values are means ± SEM (n = 5/6) of male-treated Wistar rats. Solid line range: minimum reference value; dotted line: maximum reference value. * p ≤ 0.05 versus Ctrl group; ^# p ≤ 0.05 versus Ctrl-D; ^$ p ≤ 0.05 versus BPS-D; ^& p ≤ 0.05 versus VitE-D (specific p values are included in the text).

Figure 6

Effects of vitamin E (VitE), bisphenol S (BPS), or VitE + BPS on pancreas histology, stain with H&E. Bar = 100 µm. Photomicrographs of pancreatic tissue in 4×, 10×, and 40× magnification of (a–c) Ctrl group; (d–f) Ctrl-D group; (g–i) VitE-D group; (j–l) BPS-D group; (m–o) VitE + BPS-D group. Inset in (b) indicates the 100× magnification of the exocrine parenchyma of the Ctrl group. Inset in (n) denotes the 100× magnification of the exocrine parenchyma of the VitE + BPS-D group; yellow arrows indicate vacuolization inside of cells. (p) Boxplot of the number of Langerhans islets; * p ≤ 0.05 versus Ctrl and ^& p ≤ 0.05 versus VitE-D. (q) Mean Langerhans islets area (µm²); * p ≤ 0.05 versus Ctrl (specific p values are included in the text). White arrows indicate Langerhans islets; blue stars show the pancreatic duct; the green circle exhibits the vacuolization and degeneration of the exocrine pancreas; the green arrowhead displays the lipid infiltration in Langerhans islets cells.