Wang Xinghe, Muhammad Ishfaq, Sun Xiaoqi, Han Meiyu, Hamid Sattar, Zhang Xiuying
Laboratory of Veterinary Pathology, Faculty of Basic Veterinary Science, College of Animal Science and Veterinary Medicine, Shenyang Agricultural University, Shenyang, People's Republic of China.
Heilongjiang Key Laboratory for Animal Disease Control and Pharmaceutical Development, Faculty of Basic Veterinary Science, College of Veterinary Medicine, Northeast Agricultural University, 600 Changjiang Road, Xiangfang District, Harbin, People's Republic of China.
Mol Biol Rep. 2018 Oct;45(5):881-891. doi: 10.1007/s11033-018-4234-4. Epub 2018 Jul 5.
It is well documented that liver is the primary target organ of aflatoxin B (AFB) and curcumin proved to be effective against AFB-induced liver injury. In the present study, we investigated the preventive effects of curcumin against AFB-induced apoptosis through the molecular regulation of p53, caspase-3, Bax, caspase-9, Bcl-2 and cytochrome-C associated with mitochondrial pathway. Liver antioxidant levels were measured. The hallmarks of apoptosis were analysed by methyl green-pyronin-Y staining, transmission electron microscopy, RT-PCR and western blot. Results revealed that dietary curcumin ameliorated AFB-induced oxidative stress in a dose-dependent manner. Methyl green-pyronin-Y staining and transmission electron microscopy showed that AFB induced apoptosis and caused abnormal changes in liver cells morphology such as condensation of chromatin material, reduces cell volume and damaged mitochondria. Moreover, mRNA and protein expression results manifested that apoptosis associated genes showed up-regulation in AFB fed group. However, the supplementation of dietary curcumin (dose-dependently) alleviated the increased expression of the apoptosis associated genes at mRNA and protein level, and restored the hepatocytes normal morphology. The study provides an insight and a better understanding of the preventive mechanism of curcumin against AFB-induced apoptosis in hepatocytes and provide scientific basis for the therapeutic uses of curcumin.
已有充分文献证明肝脏是黄曲霉毒素B（AFB）的主要靶器官，姜黄素被证明对AFB诱导的肝损伤有效。在本研究中，我们通过对与线粒体途径相关的p53、半胱天冬酶-3、Bax、半胱天冬酶-9、Bcl-2和细胞色素C进行分子调控，研究了姜黄素对AFB诱导的细胞凋亡的预防作用。测定了肝脏抗氧化水平。通过甲基绿-派洛宁-Y染色、透射电子显微镜、逆转录-聚合酶链反应（RT-PCR）和蛋白质免疫印迹法分析细胞凋亡的特征。结果显示，膳食姜黄素以剂量依赖的方式改善了AFB诱导的氧化应激。甲基绿-派洛宁-Y染色和透射电子显微镜显示，AFB诱导细胞凋亡并导致肝细胞形态发生异常变化，如染色质物质浓缩、细胞体积减小和线粒体受损。此外，mRNA和蛋白质表达结果表明，AFB喂养组中凋亡相关基因呈上调表达。然而，膳食姜黄素的补充（剂量依赖）在mRNA和蛋白质水平上减轻了凋亡相关基因表达的增加，并恢复了肝细胞的正常形态。本研究为深入了解姜黄素对AFB诱导的肝细胞凋亡的预防机制提供了见解，并为姜黄素的治疗应用提供了科学依据。
