赭曲霉毒素A对小鼠生长性能、氧化应激及器官蓄积的影响研究

Effects of Ochratoxin A on growth performance, oxidative stress and organ accumulation in mice

  • 摘要: 赭曲霉毒素A(Ochratoxin A, OTA)是一种广泛污染谷物及其制品的重要真菌毒素,对人和动物健康构成严重威胁。已有研究虽已明确其肝肾毒性,但其对机体多器官系统的毒害作用与机制尚未完全阐明。为探究OTA的全身毒性效应,通过建立小鼠亚急性暴露模型(每日灌胃1、2、3.5 mg/kg BW OTA,持续8 d),系统评估了OTA对小鼠生长性能、血清氧化应激水平及主要脏器(心、肝、脾、肺、肾)中残留分布的影响。结果表明:1) OTA暴露以剂量依赖方式显著抑制小鼠体重增长,且高剂量组肝脏脏器指数显著降低(P<0.05);2) 中、高剂量OTA暴露可显著降低血清总超氧化物歧化酶活力、谷胱甘肽过氧化物酶活力及总抗氧化能力(P<0.05),表明其可引发系统性氧化损伤;3) OTA在各脏器中的残留量呈器官特异性分布,其中肾脏残留量最高(高达29.4 μg/g),肺脏次之,肝脏最低,且三者均显著高于心脏与脾脏(P<0.05)。本研究证实,OTA暴露不仅损害生长性能并诱发全身性氧化应激,而且在肺脏的高蓄积现象提示肺脏可能为OTA毒理学研究的新关注靶点。上述结果为全面理解OTA的全身毒性及其机制提供了重要实验依据。

     

    Abstract: Ochratoxin A(OTA) was identified as an important mycotoxin widely contaminating cereals and their derived products, posing a serious threat to human and animal health. Although its hepatorenal toxicity had been clarified by previous studies, its toxic effects on multiple organ systems and the underlying mechanisms were not fully elucidated. To investigate the systemic toxicity of OTA, a subacute mouse exposure model(daily intragastric administration of 1, 2, 3.5 mg/kg BW OTA for 8 days) was established, and the effects of OTA on growth performance, serum oxidative stress levels, and residue distribution in major organs(heart, liver, spleen, lung, kidney) were systematically evaluated. The results showed that:1)OTA exposure significantly inhibited mouse body weight gain in a dose‑dependent manner, and the liver organ index in the high-dose group was significantly reduced(P<0.05);2)Medium‑dose and high‑dose OTA exposure significantly decreased serum total superoxide dismutase activity, glutathione peroxidase activity, and total antioxidant capacity (P<0.05),indicating that systemic oxidative damage was induced;3)Organ‑specific distribution of OTA residues was observed among the tested organs, with the highest residue level being detected in the kidney(up to 29.4 μg/g),followed by the lung and then the liver, and all three were significantly higher than those in the heart and spleen(P<0.05). It was confirmed that OTA exposure not only impaired growth performance and induced systemic oxidative stress, but also the high accumulation in the lung suggested that the lung might be a new target of concern in OTA toxicology research. These findings provided important experimental evidence for a comprehensive understanding of the systemic toxicity and mechanisms of OTA.

     

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