Ochratoxin A (OTA) is a toxin widely found in aquafeed ingredients, and hypoxia is a common problem in fish farming. In practice, aquatic animals tend to be more sensitive to hypoxia while feeds are contaminated with OTA, but no studies exist in this area. This research investigated the multiple biotoxicities of OTA and hypoxia combined on the liver of grass carp and explored the mitigating effect of curcumin (CUR). A total of 720 healthy juvenile grass carp (11.06 ± 0.05 g) were selected and assigned randomly to 4 experimental groups: control group (without OTA and CUR), 1.2 mg/kg OTA group, 400 mg/kg CUR group, and 1.2 mg/kg OTA + 400 mg/kg CUR group with three replicates each for 60 d. Subsequently, 32 fish were selected, divided into normoxia (18 fish) and hypoxia (18 fish) groups, and subjected to hypoxia stress for 96 h. CUR can attenuate histopathological damage caused by coming to OTA and hypoxia by reducing vacuolation and nuclear excursion. The alleviation of this damage was associated with the attenuation of apoptosis in the mitochondrial pathway by decreasing the expression of the pro-apoptotic proteins Caspase 3, 8, 9, Bax, and Apaf1 while increasing the expression of the anti-apoptotic protein Bcl-2, and attenuation of endoplasmic reticulum stress (ERS) by reducing Grp78 expression and chop levels. This may be attributed to the fact that the addition of CUR increased the levels of catalase (CAT) and glutathione reductase (GSH), increased antioxidant capacity, and ensured the proper functioning of respiratory chain complexes I and II, which in turn reduced the high production of reactive oxygen species (ROS), thus alleviating apoptosis and ERS. In conclusion, our data demonstrate the effectiveness of CUR in attenuating liver injury caused by the combination of OTA and hypoxia. This study confirms the feasibility and efficacy of adding natural products to mitigate toxic damage to aquatic animals.

中文翻译：

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姜黄素通过降低 ROS 含量双重靶向内质网应激和细胞凋亡，减轻草鱼 (Ctenopharyngodon idella) 赭曲霉毒素 A 和缺氧引起的肝损伤


赭曲霉毒素A（OTA）是一种广泛存在于水产饲料原料中的毒素，缺氧是养鱼业的常见问题。在实践中，水生动物往往对缺氧更加敏感，而饲料则受到OTA污染，但目前尚无这方面的研究。本研究探讨了OTA和缺氧联合对草鱼肝脏的多种生物毒性，并探讨了姜黄素（CUR）的缓解作用。选取健康草鱼幼鱼（11.06±0.05 g）720尾，随机分为4个实验组：对照组（不含OTA和CUR）、1.2 mg/kg OTA组、400 mg/kg CUR组和1.2 mg组。 /kg OTA + 400 mg/kg CUR 组，每个重复 3 个，持续 60 d。随后选取32条鱼，分为常氧组（18条鱼）和缺氧组（18条鱼），进行低氧应激96 h。 CUR 可以通过减少空泡和核偏移来减轻 OTA 和缺氧引起的组织病理学损伤。这种损伤的减轻与线粒体途径中凋亡的减弱有关，通过减少促凋亡蛋白 Caspase 3、8、9、Bax 和 Apaf1 的表达，同时增加抗凋亡蛋白 Bcl-2 的表达，并通过降低 Grp78 表达和 Chop 水平来减弱内质网应激 (ERS)。这可能是由于CUR的添加增加了过氧化氢酶（CAT）和谷胱甘肽还原酶（GSH）的水平，增加了抗氧化能力，并确保了呼吸链复合物I和II的正常功能，从而降低了高浓度活性氧 (ROS) 的产生，从而减轻细胞凋亡和 ERS。 总之，我们的数据证明了 CUR 在减轻 OTA 和缺氧联合引起的肝损伤方面的有效性。这项研究证实了添加天然产品来减轻对水生动物的毒性损害的可行性和有效性。