Laboratory of Research on Biologically Compatible Compounds, Faculty of Dentistry, Rue Avicenne, 5019 Monastir, Tunisia.
Nutr Metab (Lond). 2011 Oct 18;8:73. doi: 10.1186/1743-7075-8-73.
Aflatoxin B1 (AFB1) is potent hepatotoxic and hepatocarcinogenic agent. In aflatoxicosis, oxidative stress is a common mechanism contributing to initiation and progression of hepatic damage. The aim of this work was to evaluate the hepatoprotective effect of cactus cladode extract (CCE) on aflatoxin B1-induced liver damage in mice by measuring malondialdehyde (MDA) level, the protein carbonyls generation and the heat shock proteins Hsp 70 and Hsp 27 expressions in liver. We also looked for an eventual protective effect against AFB1-induced genotoxicity as determined by chromosome aberrations test, SOS Chromotest and DNA fragmentation assay. We further evaluated the modulation of p53, bax and bcl2 protein expressions in liver.
Adult, healthy balbC (20-25 g) male mice were pre-treated by intraperitonial administration of CCE (50 mg/Kg.b.w) for 2 weeks. Control animals were treated 3 days a week for 4 weeks by intraperitonial administration of 250 μg/Kg.b.w AFB1. Animals treated by AFB1 and CCE were divided into two groups: the first group was administrated CCE 2 hours before each treatment with AFB1 3 days a week for 4 weeks. The second group was administrated without pre-treatment with CCE but this extract was administrated 24 hours after each treatment with AFB1 3 days a week for 4 weeks.
Our results clearly showed that AFB1 induced significant alterations in oxidative stress markers. In addition, it has a genotoxic potential and it increased the expression of pro apoptotic proteins p53 and bax and decreased the expression of bcl2. The treatment of CCE before or after treatment with AFB1, showed (i) a total reduction of AFB1 induced oxidative damage markers, (ii) an anti-genotoxic effect resulting in an efficient prevention of chromosomal aberrations and DNA fragmentation compared to the group treated with AFB1 alone (iii) restriction of the effect of AFB1 by differential modulation of the expression of p53 which decreased as well as its associated genes such as bax and bcl2.
We concluded that CCE might have a hepatoprotective effect against aflatoxicosis in mice, probably acting by promoting the antioxidant defence systems.
黄曲霉毒素 B1（AFB1）是一种强烈的肝毒性和致癌物质。在黄曲霉毒素中毒中，氧化应激是导致肝损伤发生和进展的常见机制。本工作的目的是通过测量丙二醛（MDA）水平、蛋白质羰基生成以及热休克蛋白 Hsp70 和 Hsp27 在肝中的表达，评估仙人掌茎提取物（CCE）对 AFB1 诱导的肝损伤的保护作用。我们还寻找了一种可能的保护作用，以防止 AFB1 诱导的染色体畸变试验、SOS 显色试验和 DNA 片段化试验的遗传毒性。我们进一步评估了肝中 p53、bax 和 bcl2 蛋白表达的调节。
成年、健康的 balbC（20-25 克）雄性小鼠通过腹腔内给予 CCE（50mg/kg.b.w）预处理 2 周。对照动物每周 3 天腹腔内给予 250μg/kg.b.w AFB1 治疗 4 周。用 AFB1 治疗的动物分为两组：第一组在每周 3 天腹腔内给予 AFB1 前 2 小时给予 CCE 治疗 4 周。第二组未用 CCE 预处理，但在每周 3 天腹腔内给予 AFB1 后 24 小时给予该提取物治疗 4 周。
我们的结果清楚地表明，AFB1 诱导了氧化应激标志物的显著改变。此外，它具有遗传毒性潜力，并增加了促凋亡蛋白 p53 和 bax 的表达，降低了 bcl2 的表达。在 AFB1 治疗前后给予 CCE 治疗，（i）完全降低了 AFB1 诱导的氧化损伤标志物，（ii）显示出抗遗传毒性作用，与单独用 AFB1 治疗的组相比，有效地预防了染色体畸变和 DNA 片段化，（iii）通过差异调节 p53 的表达来限制 AFB1 的作用，p53 及其相关基因如 bax 和 bcl2 的表达也随之降低。
我们得出结论，CCE 可能对小鼠黄曲霉毒素中毒具有保护作用，可能通过促进抗氧化防御系统起作用。
