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Based on our repeated-measures analysis, there were no obvious signs of toxicity and no significant treatment effect on body weight, or liver-to-body weight ratios between treatment groups. Liver weight significantly increased only at 200 mg/(kg·day) of DBDPE. (Table 1)
Table 1. Body Weight, Liver Weight, and Liver-to-body Weight Ratio
Treatment Group [mg/(kg·day)] Body Weight (g)a Liver Weight (g)a Liver-to-body Weight Ratioa 0 23.08 ± 2.51 1.08 ± 0.18 0.047 ± 0.009 5 23.81 ± 2.31 1.22 ± 0.18 0.052 ± 0.006 20 23.46 ± 2.13 1.22 ± 0.21 0.052 ± 0.003 100 23.90 ± 1.95 1.21 ± 0.16 0.051 ± 0.008 200 25.65 ± 2.36 1.38 ± 0.24b 0.054 ± 0.007 Note. aData are expressed as mean ± standard deviation (n = 16). bSignificantly different from control group (P < 0.05). -
The levels of AST (Figure 1A) and ALT (Figure 1B) of different concentration treatment groups were markedly increased compared to the control group (P < 0.05). Other chemistry parameters including LDH, GGT, TBIL, IBIL, ALP, and TBA did not show significant differences compared to the control group.
Figure 1. Effects of Balb/C mouse treated by DBDPE on selected chemistry parameters including AST (A) and ALT (B). Parameters was measured by an autoanalyser. Data represent means ± standard deviation. *Statistically significant differences between treatment group and control group were determined by a one-way ANOVA (n = 16, P < 0.05).
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In comparision with control group, there was a significant increase in blood glucose levels in the treatment groups of 200 mg/(kg·day) starting from the 15th day, and 100 mg/(kg·day) from the 20th day, and 20 mg from the 30th day (Figure 2).
Figure 2. Effects of Balb/C mouse treated by DBDPE on blood glucose. Glucose was measured by a portable glucose analyzer. Data represent means ± standard deviation. *Statistically significant differences between treatment group and control group were determined by a one-way ANOVA (n = 16, P < 0.05).
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There was a weak induction in TSH, only statistically significant in the treatment group of 200 mg/(kg·day) (Figure 3A). Serum total T3 was found to have decreased significantly for 200 mg/(kg·day) (Figure 3B), serum fT3 for 100 mg/(kg·day) and 200 mg/(kg·day) (Figure 3C). There was a declining but not significant change in serum total T4 (Figure 3D), fT4 (Figure 3E) and insulin (Figure 3F) in any treatment groups.
Figure 3. Effects of Balb/C mouse treated by DBDPE on TSH (A), T3 (B), fT3 (C), T4 (D), fT4 (E), and insulin (F). TSH, T3, fT3, T4, fT4, and insulin were measured by standard kits. Data represent means ± standard deviation. *Statistically significant differences between treatment group and control group were determined by a one-way ANOVA (n = 16, P < 0.05).
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Effects on major xenobiotic metabolizing enzymes for phase Ⅰ metabolism were examined. UDPGT and PROD activities were found to have been increased significantly for 100 mg/(kg·day) and 200 mg/(kg·day) (Figure 4A and 4C), and EROD activity for 200 mg/(kg·day) (Figure 4B). Compared to the control group, no significant changes were observed in BROD activity in all treatment groups (Figure 4D).
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Histopathologic liver changes were characterized by hepatocyte hypertrophy and cytoplasmic vacuolization in mice treated in high exposure dose (Figure 5B). No histopathological change of thyroid was observed in mice (Figure 5A).
Figure 5. Thyroid gland from a mouse of the exposure group of 5 mg/(kg·day) (A2), 20 mg/(kg·day) (A3), 100 mg/(kg·day) (A4), and 200 mg/(kg·day) (A5) shown no significant change compared with the control group (A1). Liver from a mouse of the exposure group of 5 mg/(kg·day) (B2), 20 mg/(kg·day) (B3), and 100 mg/(kg·day) (B4) shown no significant change compared with the control group (B1). Liver from a mouse of the exposure group of 200 mg/(kg·day) (B5) show histopathologic liver changes characterized by hepatocyte hypertrophy and cytoplasmic vacuolization.
doi: 10.3967/bes2018.002
Endocrine Disruption Activity of 30-day Dietary Exposure to Decabromodiphenyl Ethane in Balb/C Mouse
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Abstract:
Objective This study aimed to evaluate the hepatotoxicity, metabolic disturbance activity and endocrine disrupting activity of mice treated by Decabromodiphenyl ethane (DBDPE). Methods In this study, Balb/C mice were treated orally by gavage with various doses of DBDPE. After 30 days of treatment, mice were sacrificed; blood, livers and thyroid glands were obtained, and hepatic microsomes were isolated. Biochemical parameters including 8 clinical chemistry parameters, blood glucose and hormone levels including insulin and thyroid hormone were assayed. The effects of DBDPE on hepatic cytochrome P450 (CYP) levels and activities and uridinediphosphate-glucuronosyltransferase (UDPGT) activities were investigated. Liver and thyroid glands were observed. Results There were no obvious signs of toxicity and no significant treatment effect on body weight, or liver-to-body weight ratios between treatment groups. The levels of ALT and AST of higher dose treatment groups were markedly increased. Blood glucose levels of treatment groups were higher than those of control group. There was also an induction in TSH, T3, and fT3. UDPGT, PROD, and EROD activities were found to have been increased significantly in the high dose group. Histopathologic liver changes were characterized by hepatocyte hypertrophy and cytoplasmic vacuolization. Our findings suggest that DBDPE can cause a certain degree of mouse liver damage and insufficiency. Conclusion DBDPE has the activity of endocrine disruptors in Bal/C mice, which may induce drug-metabolizing enzymes including CYPs and UDPGT, and interfere with thyroid hormone levels mediated by AhR and CAR signaling pathways. Endocrine disrupting activity of DBDPE could also affect the glucose metabolism homeostasis. -
Figure 1. Effects of Balb/C mouse treated by DBDPE on selected chemistry parameters including AST (A) and ALT (B). Parameters was measured by an autoanalyser. Data represent means ± standard deviation. *Statistically significant differences between treatment group and control group were determined by a one-way ANOVA (n = 16, P < 0.05).
Figure 2. Effects of Balb/C mouse treated by DBDPE on blood glucose. Glucose was measured by a portable glucose analyzer. Data represent means ± standard deviation. *Statistically significant differences between treatment group and control group were determined by a one-way ANOVA (n = 16, P < 0.05).
Figure 3. Effects of Balb/C mouse treated by DBDPE on TSH (A), T3 (B), fT3 (C), T4 (D), fT4 (E), and insulin (F). TSH, T3, fT3, T4, fT4, and insulin were measured by standard kits. Data represent means ± standard deviation. *Statistically significant differences between treatment group and control group were determined by a one-way ANOVA (n = 16, P < 0.05).
Figure 5. Thyroid gland from a mouse of the exposure group of 5 mg/(kg·day) (A2), 20 mg/(kg·day) (A3), 100 mg/(kg·day) (A4), and 200 mg/(kg·day) (A5) shown no significant change compared with the control group (A1). Liver from a mouse of the exposure group of 5 mg/(kg·day) (B2), 20 mg/(kg·day) (B3), and 100 mg/(kg·day) (B4) shown no significant change compared with the control group (B1). Liver from a mouse of the exposure group of 200 mg/(kg·day) (B5) show histopathologic liver changes characterized by hepatocyte hypertrophy and cytoplasmic vacuolization.
Table 1. Body Weight, Liver Weight, and Liver-to-body Weight Ratio
Treatment Group [mg/(kg·day)] Body Weight (g)a Liver Weight (g)a Liver-to-body Weight Ratioa 0 23.08 ± 2.51 1.08 ± 0.18 0.047 ± 0.009 5 23.81 ± 2.31 1.22 ± 0.18 0.052 ± 0.006 20 23.46 ± 2.13 1.22 ± 0.21 0.052 ± 0.003 100 23.90 ± 1.95 1.21 ± 0.16 0.051 ± 0.008 200 25.65 ± 2.36 1.38 ± 0.24b 0.054 ± 0.007 Note. aData are expressed as mean ± standard deviation (n = 16). bSignificantly different from control group (P < 0.05). -
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