Monmeesil Poempool, Fungfuang Wirasak, Tulayakul Phitsanu, Pongchairerk Urai
Department of Anatomy, Faculty of Veterinary Medicine, Kasetsart University, 50 Ngamwongwan Road, Ladyao, Jatuchak, Bangkok 10900, Thailand.
Department of Zoology, Faculty of Science, Kasetsart University, 50 Ngamwongwan Road, Ladyao, Jatuchak, Bangkok 10900, Thailand.
J Vet Med Sci. 2019 Aug 24;81(8):1162-1172. doi: 10.1292/jvms.18-0690. Epub 2019 Jul 3.
The metabolism of aflatoxin B (AFB) generates reactive oxygen species (ROS) that destroys hepatocytes. Meanwhile, astaxanthin (AX) is known to have stronger antioxidative activity than other carotenoids. This study aimed to investigate hepatoprotective role of AX from AFB-induced toxicity in rat by histopathological study and immunohistochemistry of Cu/Zn-SOD (SOD1) which acts as the first enzyme in antioxidative reaction against cell injury from ROS. Twenty Wistar rats were randomly divided into 4 groups. The control and AFB groups were gavaged by water for 7 days followed by a single DMSO and 1 mg/kg AFB, respectively. The AXL+ AFB and AXH+ AFB groups were given of 5 mg/kg and 100 mg/kg AX for 7 days before 1 mg/kg AFB administration. The result showed significantly elevated liver weight per 100 g body weight in AFB group. The histopathological finding revealed vacuolar degeneration, necrosis, megalocytosis and binucleation of hepatocytes with bile duct hyperplasia in AFB group. The severities of pathological changes were sequentially reduced in AXL+AFB and AXH+AFB groups. Most rats in AXH+AFB group owned hypertrophic hepatocytes and atypical proliferation of cholangiocytes which are adaptive responses to severe hepatocyte damage. The SOD1 expression was also significantly higher in AXH+AFB group than solely treated AFB and AXL+AFB groups. In conclusion, AX alleviated AFB-induced liver damage in rat by stimulating SOD1 expression and transdifferentiation of cholangiocytes in dose dependent manner.
黄曲霉毒素B（AFB）的代谢会产生活性氧（ROS），从而破坏肝细胞。同时，已知虾青素（AX）具有比其他类胡萝卜素更强的抗氧化活性。本研究旨在通过组织病理学研究以及对铜/锌超氧化物歧化酶（SOD1）进行免疫组织化学分析，探讨AX对大鼠AFB诱导毒性的肝脏保护作用，SOD1是抗氧化反应中抵御ROS所致细胞损伤的首个酶。20只Wistar大鼠被随机分为4组。对照组和AFB组分别用蒸馏水灌胃7天，随后分别给予单一二甲基亚砜和1 mg/kg AFB。AXL + AFB组和AXH + AFB组在给予1 mg/kg AFB前7天分别给予5 mg/kg和100 mg/kg AX。结果显示，AFB组每100 g体重的肝脏重量显著增加。组织病理学检查发现，AFB组肝细胞出现空泡变性、坏死、巨细胞形成和双核化，伴有胆管增生。AXL + AFB组和AXH + AFB组的病理变化严重程度依次降低。AXH + AFB组的大多数大鼠肝细胞肥大，胆管细胞非典型增生，这是对严重肝细胞损伤的适应性反应。AXH + AFB组的SOD1表达也显著高于单纯AFB组和AXL + AFB组。总之，AX通过刺激SOD1表达以及胆管细胞的转分化，以剂量依赖的方式减轻大鼠AFB诱导的肝损伤。
