Romualdo Guilherme R, Goto Renata L, Fernandes Ana A H, Cogliati Bruno, Barbisan Luis F
UNESP - São Paulo State University, Botucatu Medical School, Department of Pathology, Botucatu, São Paulo State, Brazil.
UNESP - São Paulo State University, Institute of Biosciences of Botucatu, Department of Morphology, Botucatu, São Paulo State, Brazil.
Food Chem Toxicol. 2017 Sep;107(Pt A):27-36. doi: 10.1016/j.fct.2017.06.030. Epub 2017 Jun 17.
Hexachlorobezene (HCB), a fungicide widely distributed in the environment, promotes the development of hepatocellular preneoplastic lesions (PNL) and tumors in rodents. In contrast, vitamin D (VD) supplementation presents a potential role for the prevention/treatment of chronic liver diseases. Thus, we investigated whether VD supplementation attenuates the early stage of HCB-promoted hepatocarcinogenesis. Female Balb/C mice were injected a single dose of diethylnitrosamine (DEN, 50 mg/kg) at postnatal day 15. From day 40 onwards, mice were fed with a standard diet containing 0.02% HCB alone or supplemented with VD (10,000 or 20,000 IU/Kg diet) for 20 weeks. Untreated mice were fed just standard diet. After this period, mice were euthanized and liver and serum samples were collected. Compared to the untreated group, DEN/HCB treatment decreased total hepatic glutathione levels and glutathione peroxidase (GSH-Px) activity while increased lipid peroxidation, p65 protein expression, cell proliferation/apoptosis and the PNL development. In contrast, dietary VD supplementation enhanced vitamin D receptor (VDR) protein expression, total glutathione levels and GSH-Px activity while diminished lipid hydroperoxide levels. Also, VD supplementation decreased p65 protein expression, hepatocyte proliferation, the size and the liver area occupied by PNL. Therefore, our findings indicate that VD supplementation attenuates the early stage of HCB-promoted hepatocarcinogenesis.
六氯苯（HCB）是一种广泛分布于环境中的杀菌剂，可促进啮齿动物肝细胞癌前病变（PNL）和肿瘤的发展。相比之下，补充维生素D（VD）对慢性肝病的预防/治疗具有潜在作用。因此，我们研究了补充VD是否能减轻HCB促进的肝癌发生的早期阶段。在出生后第15天，给雌性Balb/C小鼠注射单剂量的二乙基亚硝胺（DEN，50 mg/kg）。从第40天起，小鼠被喂食仅含0.02% HCB的标准饮食或补充VD（10,000或20,000 IU/Kg饮食），持续20周。未处理的小鼠仅喂食标准饮食。在此期间过后，对小鼠实施安乐死并收集肝脏和血清样本。与未处理组相比，DEN/HCB处理降低了肝脏总谷胱甘肽水平和谷胱甘肽过氧化物酶（GSH-Px）活性，同时增加了脂质过氧化、p65蛋白表达、细胞增殖/凋亡以及PNL的发展。相比之下，饮食中补充VD增强了维生素D受体（VDR）蛋白表达、总谷胱甘肽水平和GSH-Px活性，同时降低了脂质过氧化氢水平。此外，补充VD降低了p65蛋白表达、肝细胞增殖、PNL的大小和肝脏所占面积。因此，我们的研究结果表明，补充VD可减轻HCB促进的肝癌发生的早期阶段。
