Objective Insulin resistance is fundamental to the development of diabetes mellitus type 2 and multiple chronic metabolic diseases, and is closely linked to environmental factors. Di(2-ethylhexyl) phthalate (DEHP) as a common plastcizer has been widely applied in plastc products and thus widely present in environment, while epidemiological studies have shown that DEHP exposure is associated with chronic diseases such as diabetes mellitus type 2 and obesity. This experiment is conducted to observe the toxic effects of DEHP on glycolipid metabolism, insulin resistance, and oxidatve stress in healthy male rats.
Methods Twenty-four healthy SPF male Wistar rats were randomly divided into four groups by weight, including one control group (corn oil) and three experimental groups treated with 10 mg/kg, 100 mg/kg, and 1 000 mg/kg DEHP by gavage (5 mL/kg), once a day, for 30 consecutve days. Tail venous blood was collected to measure random blood glucose on the 1st, 14th, and 28th days, and the changes of glucose tolerance of rats were observed by oral glucose tolerance test on the 29th day. All rats were detected for fastng plasma glucose (FPG) on the next day of last exposure, and then anesthetzed and sacrifced to weigh liver and calculate liver coefcient. The serum levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), albumin (ALB), and triglyceride (TG) were determined with auto-biochemical analyzer; the fastng insulin (FINS) was measured by radio-immunological method; the serum levels of free faty acids (FFA), malondialdehyde (MDA), and hydrogen peroxide (H2O2) were determined by colorimetry.
Results The designed DEHP exposure had no signifcant effect on body weight and food intake of rats (P>0.05). On the 14th and 28th days, the 1000mg/kg DEHP group showed increased random blood glucose compared with the control group (P < 0.05). With the increase of DEHP dose, the peak of glucose tolerance curve was heightened, but no difference in the area under curve of glucose among the groups were observed (P>0.05). Compared with the control group(3.03±0.33)%, the liver coefcients increased signifcantly in the three DEHP exposure groups(3.16±0.18)%, (3.68±0.29)%, and (5.02±0.46)%, respectvely (P < 0.05). The serum levels of ALB in the 100mg/kg and 1000mg/kg DEHP groups were higher than that in the control group (P < 0.05); the serum levels of TG in the groups treated with various doses of DEHP were increased (P < 0.05); the serum levels of ALP and ALT in the 1 000 mg/kg DEHP group were higher (P < 0.05); no difference in serum AST was observed (P>0.05). There were no signifcant changes in FPG, FINS, and index of homeostasis model assessment of insulin resistance afer designed DEHP exposures compared with the control group (P>0.05). The serum levels of FFA and H2O2 of the 1 000 mg/kg DEHP group were signifcantly higher than those of the control group (P < 0.05), but there was no signifcant difference in serum MDA (P>0.05).
Conclusion DEHP exposure at 100-1 000 mg/kg could lead to liver damage, altered glucose tolerance, glycolipid metabolism disorder, and increased oxidatve stress in male Wistar rats.
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