Laboratory of Cell and Molecular Biology, Faculty of Biological Sciences, University of Sciences and Technology Houari Boumediene (USTHB), Algiers, Algeria; Biochemistry Department, Faculty of Sciences, Ege University, Izmir, Turkey.
Laboratory of Cell and Molecular Biology, Faculty of Biological Sciences, University of Sciences and Technology Houari Boumediene (USTHB), Algiers, Algeria.
J Trace Elem Med Biol. 2018 May;47:21-30. doi: 10.1016/j.jtemb.2018.01.009. Epub 2018 Feb 4.
Zinc is a trace element widely known for its marked antioxidant properties. To gain more insight into the site- and time- specific mechanisms by which it induces chemoprevention, this study was elaborated over a pre-cancerous model of colon carcinogenesis. Colon cancer was induced by 1,2-dimethylhydrazine (DMH) in mice (20 mg/kg for 2 weeks) and groups of animals were supplemented with or without zinc sulfate (ZnSO, 200 mg/L) in drinking water for 4, 10 or 14 weeks. Colon tissues were collected for pathological observation, analyzing aberrant crypt (AC) and aberrant crypt foci (ACF) formations, multiplicity and distribution. Similarly, histological assessment and mucin production, as well as oxidative stress markers estimation was performed for the different groups. Results showed a significant increase in ACF and AC numbers, ACF multiplicity and demonstrated stronger distal occurrence than in the proximal after DHM administration. Histopathological analysis presented marked structural alterations and mucin loss in the distal than the proximal colons. A significant increase in myeloperoxidase (MPO), nitric oxide (NO), L-ornithine and malondialdehyde (MDA) levels was observed followed by a significant decrease in antioxidant markers (superoxide dismutase (SOD), catalase (CAT) and reduced glutathione (GSH)). Oral ZnSO supplementation (continuous or partial) induced significant decrease in ACF, AC numbers and multiplicity, restored histological architecture and mucin production, and a significant decrease in proinflammatory markers while it reduced antioxidants to normal levels. From this study, insight was obtained on the use of ZnSO as a chemopreventive agent and shed light on its potential, as a supplement in nutraceutical approaches.
锌是一种微量元素，以其显著的抗氧化特性而广为人知。为了更深入地了解其诱导化学预防的特定部位和时间的机制，本研究在结肠癌发生的癌前模型上进行了阐述。通过 1,2-二甲基肼（DMH）（20mg/kg，2 周）诱导小鼠发生结肠癌，并用饮水补充硫酸锌（ZnSO，200mg/L），连续或部分补充 4、10 或 14 周。收集结肠组织进行病理观察，分析异常隐窝（AC）和异常隐窝病灶（ACF）的形成、多发性和分布。同样，对不同组进行组织学评估和粘蛋白产生以及氧化应激标志物的估计。结果显示，ACF 和 AC 数量、ACF 多发性显著增加，并且在 DMH 给药后，远侧比近侧更频繁地发生。组织病理学分析显示，远侧结肠比近侧结肠结构变化更明显，粘蛋白丢失更明显。髓过氧化物酶（MPO）、一氧化氮（NO）、L-鸟氨酸和丙二醛（MDA）水平显著增加，随后抗氧化标记物（超氧化物歧化酶（SOD）、过氧化氢酶（CAT）和还原型谷胱甘肽（GSH））水平显著降低。口服硫酸锌（ZnSO）连续或部分补充可显著减少 ACF、AC 数量和多发性，恢复组织学结构和粘蛋白产生，降低促炎标志物水平，同时将抗氧化剂降低至正常水平。本研究深入了解了 ZnSO 作为化学预防剂的用途，并揭示了其作为营养保健品补充剂的潜力。
