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大鼠给予2-甲氧基乙醇后肝脏的氧化应激、促炎细胞因子上调、凋亡和致癌标志物情况。

Hepatic oxidative stress, up-regulation of pro-inflammatory cytokines, apoptotic and oncogenic markers following 2-methoxyethanol administrations in rats.

作者信息

Somade Oluwatobi T, Ajayi Babajide O, Olunaike Oyinkansola E, Jimoh Latifah A

机构信息

Department of Biochemistry, College of Biosciences, Federal University of Agriculture, Abeokuta, Nigeria.

Department of Chemical Sciences, Faculty of Natural Sciences, Ajayi Crowther University, Oyo, Nigeria.

出版信息

Biochem Biophys Rep. 2020 Aug 29;24:100806. doi: 10.1016/j.bbrep.2020.100806. eCollection 2020 Dec.

Abstract

2-methoxyethanol (2-ME) is an organic solvent widely used in the manufacture of brake fluids, paints, resins, varnish, nail polish, acetate cellulose, wood coloring, and as a plasticizer in plastics manufacturing. We therefore, investigated its effect on the liver, in a time-course study in male Wistar rats. Animals were orally administered 50 mg/kg body weight of 2-ME for a period of 7, 14, and 21 days. Following 7 days of administration of 2-ME, there was a significant increase in the level of Bax, c-Myc, K-Ras, TNF-α, IL-1β, IL-6, MDA and GPx activity, while the levels of Bcl-2, NO and GSH were significantly reduced compared with control. At the end of 14 days exposure, Bcl-2, and GSH levels, as well as GST activity, were significantly decreased, while levels of Bax, c-Myc, K-Ras, caspase-3, TNF-α, IL-1β, IL-6, MDA and NO were significantly increased compared with control. After 21 days of 2-ME administration, Bcl-2, IL-10, and GSH levels, as well as SOD and GST activities, were significantly decreased, while levels of Bax, c-Myc, K-Ras, caspase-3, p53, TNF-α, IL-1β, IL-6, MDA and NO were significantly increased compared with control. Lastly, liver histopathology confirmed and corroborated the biochemical findings reported above. We therefore, advised that exposures to 2-ME should be strictly avoided as it could trigger hepatic damage through the disorganization of the antioxidant system, up-regulation of inflammatory, apoptotic, and oncogenic markers in rats.

摘要

2-甲氧基乙醇(2-ME)是一种有机溶剂,广泛应用于制动液、油漆、树脂、清漆、指甲油、醋酸纤维素、木材染色的生产中,还用作塑料制造中的增塑剂。因此,我们在雄性Wistar大鼠的一项时间进程研究中,研究了其对肝脏的影响。给动物口服50毫克/千克体重的2-ME,持续7天、14天和21天。在给予2-ME 7天后,Bax、c-Myc、K-Ras、TNF-α、IL-1β、IL-6、丙二醛(MDA)水平和谷胱甘肽过氧化物酶(GPx)活性显著增加,而与对照组相比,Bcl-2、一氧化氮(NO)和谷胱甘肽(GSH)水平显著降低。在暴露14天结束时,Bcl-2和GSH水平以及谷胱甘肽S-转移酶(GST)活性显著降低,而与对照组相比,Bax、c-Myc、K-Ras、半胱天冬酶-3(caspase-3)、TNF-α、IL-1β、IL-6、MDA和NO水平显著增加。在给予2-ME 21天后,Bcl-2、IL-10和GSH水平以及超氧化物歧化酶(SOD)和GST活性显著降低,而与对照组相比,Bax、c-Myc、K-Ras、caspase-3、p53、TNF-α、IL-1β、IL-6、MDA和NO水平显著增加。最后,肝脏组织病理学证实并支持了上述生化研究结果。因此,我们建议应严格避免接触2-ME,因为它可能通过破坏大鼠抗氧化系统、上调炎症、凋亡和致癌标志物而引发肝损伤。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3f66/7472863/8a0123da48ff/gr1.jpg

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