Ashokkumar Pandurangan, Sudhandiran Ganapasam
Department of Biochemistry, University of Madras, Guindy Campus, Chennai 600 025, Tamilnadu, India.
Biomed Pharmacother. 2008 Nov;62(9):590-7. doi: 10.1016/j.biopha.2008.06.031. Epub 2008 Jul 9.
The modifying effect of dietary exposure to a flavonoid, luteolin (LUT) during the azoxymethane (AOM)-induced colon carcinogenesis was investigated in this study. Aberrant crypt foci (ACF), lipid peroxidation (LPO), enzymic and non-enzymic antioxidants and histopathological analysis were performed. Colon carcinogenesis was induced by injecting 15 mg/body kg weight of AOM, intraperitoneally (i.p.), once in a week for 3 weeks in male Balb/c mice. AOM-induced mice were treated with LUT (1.2mg of LUT/kg body weight/day orally). After the experimental period, frequency of ACF, levels of thiobarbutaric acid reactive substances (TBARS) and hydroxy radical (OH ) were found to be increased, whereas glutathione (GSH), Vitamins C, E and A were decreased in the plasma and colon of AOM-induced mice. However, LUT treatment to AOM-induced mice significantly decreased the incidence of ACF, levels of TBARS and OH with a concordant increase in non-enzymic antioxidants in plasma and colon tissue. The activities of the antioxidant enzymes such as superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and glutathione reductase (GR) were found to be decreased due to the induction of colon cancer in mouse. LUT treatment ameliorated the activities of these antioxidant enzymes. The histological study revealed a significant increase in the enlarged nuclei and hyperchromatism of cells in AOM-induced mice whereas LUT significantly reduced the signs in the colon. The immunohistochemical expression of MDA-DNA adduct was studied. In AOM-induced group, the expression was increased and treatment with LUT decreased significantly. The present study depicts that LUT can act as an effective chemopreventive agent against colon cancer.
本研究调查了饮食中黄酮类化合物木犀草素（LUT）在偶氮甲烷（AOM）诱导的结肠癌发生过程中的修饰作用。进行了异常隐窝灶（ACF）、脂质过氧化（LPO）、酶促和非酶促抗氧化剂以及组织病理学分析。通过腹腔注射（i.p.）15mg/体重kg的AOM诱导雄性Balb/c小鼠发生结肠癌，每周一次，共3周。用LUT（1.2mg LUT/体重kg/天，口服）对AOM诱导的小鼠进行治疗。实验期结束后，发现AOM诱导的小鼠血浆和结肠中ACF的频率、硫代巴比妥酸反应性物质（TBARS）和羟基自由基（OH）水平升高，而谷胱甘肽（GSH）、维生素C、E和A水平降低。然而，用LUT治疗AOM诱导的小鼠可显著降低ACF的发生率、TBARS和OH水平，同时血浆和结肠组织中的非酶促抗氧化剂含量相应增加。由于小鼠结肠癌的诱导，超氧化物歧化酶（SOD）、过氧化氢酶（CAT）、谷胱甘肽过氧化物酶（GPx）和谷胱甘肽还原酶（GR）等抗氧化酶的活性降低。LUT治疗改善了这些抗氧化酶的活性。组织学研究显示，AOM诱导的小鼠细胞核增大和细胞色素沉着显著增加，而LUT显著减轻了结肠中的这些症状。研究了MDA-DNA加合物的免疫组化表达。在AOM诱导组中，表达增加，而LUT治疗后显著降低。本研究表明，LUT可作为一种有效的结肠癌化学预防剂。
