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N-乙酰-L-半胱氨酸(L-NAC)对苯乙烯诱导的耳蜗损伤的保护作用。

Protective effect of N-acetyl-L-cysteine (L-NAC) against styrene-induced cochlear injuries.

作者信息

Yang Wei Ping, Hu Bo Hua, Chen Guang Di, Bielefeld Eric C, Henderson Donald

机构信息

Center for Hearing and Deafness, SUNY at Buffalo, Buffalo, New York 14214, USA.

出版信息

Acta Otolaryngol. 2009 Oct;129(10):1036-43. doi: 10.1080/00016480802566261.

Abstract

CONCLUSION

Styrene exposure causes hair cell death through both apoptotic and necrotic pathways and treatment with N-acetyl-L-cysteine (L-NAC) reduces styrene ototoxicity.

OBJECTIVE

Exposure to styrene causes hearing loss and hair cell death in the middle frequency region in the cochlea. The current study was designed to examine the cell death pathways and the protective effect of L-NAC against styrene-induced cochlear injuries.

MATERIALS AND METHODS

Seventeen rats were exposed to styrene by gavage at 400 mg/kg 5 days per week for 3 weeks. Nine of the styrene-treated rats received L-NAC by intraperitoneal injection (325 mg/kg), and the remaining eight rats received saline injections as controls. The styrene-induced hearing loss was assessed by auditory brainstem responses (ABRs). Apoptotic, necrotic, and missing hair cells were quantified using combined methods, including nuclear staining with propidium iodide, F-actin staining with FITC-phalloidin, and the TUNEL assay.

RESULTS

The styrene exposure caused a threshold shift of 15±4.3 dB. Both apoptosis and necrosis were involved in the pathogenesis of the cochlear lesion, but apoptosis appeared to be the major cell death pathway leading to the styrene ototoxicity. Treatment with L-NAC reduced the number of missing and dying outer hair cells (OHCs) and reduced the styrene-induced hearing loss.

摘要

结论

苯乙烯暴露通过凋亡和坏死途径导致毛细胞死亡,而用N-乙酰-L-半胱氨酸(L-NAC)治疗可降低苯乙烯的耳毒性。

目的

接触苯乙烯会导致耳蜗中频区域听力损失和毛细胞死亡。本研究旨在探讨细胞死亡途径以及L-NAC对苯乙烯诱导的耳蜗损伤的保护作用。

材料与方法

17只大鼠每周5天经口灌胃给予400mg/kg苯乙烯,持续3周。9只经苯乙烯处理的大鼠腹腔注射L-NAC(325mg/kg),其余8只大鼠注射生理盐水作为对照。通过听性脑干反应(ABR)评估苯乙烯诱导的听力损失。使用包括碘化丙啶核染色、FITC-鬼笔环肽F-肌动蛋白染色和TUNEL检测在内的联合方法对凋亡、坏死和缺失的毛细胞进行定量。

结果

苯乙烯暴露导致阈值偏移15±4.3dB。凋亡和坏死均参与了耳蜗病变的发病机制,但凋亡似乎是导致苯乙烯耳毒性的主要细胞死亡途径。L-NAC治疗减少了缺失和死亡的外毛细胞(OHC)数量,并减轻了苯乙烯诱导的听力损失。

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Int Arch Occup Environ Health. 2006 Feb;79(2):93-102. doi: 10.1007/s00420-005-0030-2. Epub 2005 Sep 6.
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