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90 天经口给予 ICR 小鼠 N,N-二甲基甲酰胺导致的肝和心脏毒性。

Liver and heart toxicity due to 90-day oral exposure of ICR mice to N,N-dimethylformamide.

机构信息

School of Public Health, Anhui Medical University, China.

出版信息

Environ Toxicol Pharmacol. 2011 May;31(3):357-63. doi: 10.1016/j.etap.2011.01.002. Epub 2011 Jan 28.

Abstract

N,N-dimethylformamide (DMF) is a colorless liquid with a faint amine odor, which is widely used in the world. DMF exposure may induce adverse effects on liver, but few studies showed damage to heart after exposure to DMF. In the present study, DMF was administered to ICR mice with the doses of 0.32, 0.63 and 1.26 g/kg of body weight by gavage for 90 days. The increase in the relative liver weight is accompanied with the presence of the centrilobular hepatocellular hypertrophy as well as increased serum levels of aspartate transaminase (AST) and alanine transaminase (ALT). An increase of malondialdehyde (MDA) level was shown in liver homogenate, while superoxide dismutase (SOD) and glutathione (GSH) activities decreased. Heart damage was also shown in mice exposed to DMF for 90 days, although pathological examination showed only slight inflammatory cell infiltration. Increased levels of serum lactate dehydrogenase (LDH), isoenzymes of creatine kinase (CK-MB) and cardiac troponin I (cTnI) were shown. Increased level of MDA was also shown in heart homogenate, in contrast with the decreased activity of SOD. These data suggested that the administration of DMF could induce liver and heart injuries and oxidative stress was involved in the toxic effects.

摘要

N,N-二甲基甲酰胺(DMF)是一种无色液体,具有微弱的胺气味,在世界范围内广泛使用。DMF 暴露可能会对肝脏造成不良影响,但很少有研究表明 DMF 暴露会对心脏造成损害。在本研究中,将 DMF 以 0.32、0.63 和 1.26 g/kg 体重的剂量通过灌胃给予 ICR 小鼠,持续 90 天。相对肝重的增加伴随着中央小叶肝细胞肥大以及天冬氨酸转氨酶(AST)和丙氨酸转氨酶(ALT)血清水平的升高。肝匀浆中丙二醛(MDA)水平升高,而过氧化物歧化酶(SOD)和谷胱甘肽(GSH)活性降低。暴露于 DMF 90 天的小鼠也出现了心脏损伤,尽管病理检查仅显示轻微的炎症细胞浸润。血清乳酸脱氢酶(LDH)、肌酸激酶同工酶(CK-MB)和心肌肌钙蛋白 I(cTnI)的水平升高。心脏匀浆中 MDA 水平也升高,而 SOD 活性降低。这些数据表明,DMF 的给药可诱导肝和心脏损伤,氧化应激参与其毒性作用。

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