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甲基硒酸通过抑制氧化应激和失活 p53 和 MAPKs 来预防棒曲霉素诱导的肝毒性和肾毒性。

Methylseleninic Acid Prevents Patulin-Induced Hepatotoxicity and Nephrotoxicity via the Inhibition of Oxidative Stress and Inactivation of p53 and MAPKs.

机构信息

Beijing Advanced Innovation Center for Food Nutrition and Human Health, College of Food Science and Nutritional Engineering, Beijing Key Laboratory for Food Non-thermal Processing, China Agricultural University , No. 17 Qinghua East Road, Haidian District, Beijing 100083, China.

College of Veterinary Medicine, China Agricultural University , No. 2 Yuanmingyuan West Road, Haidian District, Beijing 100193, China.

出版信息

J Agric Food Chem. 2017 Jul 5;65(26):5299-5305. doi: 10.1021/acs.jafc.7b01338. Epub 2017 Jun 22.

DOI:10.1021/acs.jafc.7b01338
PMID:28594550
Abstract

Patulin is one of the common food-borne mycotoxins. Previous studies have demonstrated that patulin can cause diverse toxic effects in animals including hepatotoxicity and nephrotoxicity. In the present study, we have addressed the protective effect of two forms of selenium compounds methylseleninic acid (MSeA) and sodium selenite on patulin-induced nephrotoxicity and hepatotoxicity using both in vitro and in vivo models. Results showed that MSeA at concentrations of 3-5 μM, not sodium selenite at the same concentrations, is capable of protecting against patulin-induced cytotoxicity in the cell culture model. Moreover, the hepatoprotective and nephroprotective effects of MSeA (2 mg/kg body weight, oral administration) on patulin-induced toxicity (10 mg/kg body weight, intraperitoneal injection) were also achieved in the animal model. A further mechanistic study revealed that the protective effect of MSeA on patulin-mediated toxicity is attributed to its ability to inhibit patulin-mediated ROS generation and inactivate p53 and mitogen-activated protein kinase (MAPK) signaling pathways. Our findings support a possible usefulness of MSeA as a novel detoxicant to mitigate the toxicities of patulin.

摘要

棒曲霉素是一种常见的食物源真菌毒素。先前的研究表明,棒曲霉素会对动物造成多种毒性作用,包括肝毒性和肾毒性。在本研究中,我们采用体外和体内模型,研究了两种硒化合物形式——甲基硒酸(MSeA)和亚硒酸钠对棒曲霉素诱导的肾毒性和肝毒性的保护作用。结果表明,浓度为 3-5 μM 的 MSeA(而非相同浓度的亚硒酸钠)能够在细胞培养模型中抵抗棒曲霉素诱导的细胞毒性。此外,MSeA(2 毫克/千克体重,口服)对(10 毫克/千克体重,腹腔注射)棒曲霉素诱导的毒性也具有肝保护和肾保护作用。进一步的机制研究表明,MSeA 对棒曲霉素介导毒性的保护作用归因于其抑制棒曲霉素介导的 ROS 生成以及失活 p53 和丝裂原活化蛋白激酶(MAPK)信号通路的能力。我们的研究结果支持 MSeA 作为一种新型解毒剂减轻棒曲霉素毒性的可能性。

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