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十溴二苯乙烷经 30 天喂养暴露对 Balb/C 小鼠的内分泌干扰活性

Endocrine Disruption Activity of 30-day Dietary Exposure to Decabromodiphenyl Ethane in Balb/C Mouse.

机构信息

Institute of Disease Prevention and Control, Chinese People's Liberation Army, Beijing 100071, China.

Institute of Health and Environmental Medicine, Academy Military Medical Sciences, Tianjin 300050, China.

出版信息

Biomed Environ Sci. 2018 Jan;31(1):12-22. doi: 10.3967/bes2018.002.

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.

摘要

目的

本研究旨在评估十溴二苯乙烷(DBDPE)处理的小鼠的肝毒性、代谢紊乱活性和内分泌干扰活性。

方法

在这项研究中,Balb/C 小鼠通过灌胃给予不同剂量的 DBDPE。治疗 30 天后,处死小鼠;采集血液、肝脏和甲状腺,并分离肝微粒体。测定包括 8 项临床化学参数在内的生化参数、血糖和激素水平(包括胰岛素和甲状腺激素)。研究了 DBDPE 对肝细胞色素 P450(CYP)水平和活性以及尿苷二磷酸葡萄糖醛酸转移酶(UDPGT)活性的影响。观察了肝脏和甲状腺的变化。

结果

各剂量组均未出现明显毒性迹象,体重或肝体比与对照组相比无明显差异。较高剂量组的 ALT 和 AST 水平显著升高。各剂量组的血糖水平均高于对照组。TSH、T3 和 fT3 也有所升高。高剂量组的 UDPGT、PROD 和 EROD 活性显著增加。组织病理学肝脏变化的特征是肝细胞肥大和细胞质空泡化。研究结果表明,DBDPE 可导致小鼠肝脏受到一定程度的损伤和功能不全。

结论

DBDPE 在 Balb/C 小鼠中具有内分泌干扰活性,可能诱导包括 CYP 和 UDPGT 在内的药物代谢酶,并干扰 AhR 和 CAR 信号通路介导的甲状腺激素水平。DBDPE 的内分泌干扰活性还可能影响葡萄糖代谢的稳态。

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