1α,25-二羟基维生素D3可预防二乙基亚硝胺诱导并由苯巴比妥促进的大鼠肝癌发生过程中的DNA损伤，并恢复抗氧化酶。
1alpha, 25-dihydroxyvitamin D3 prevents DNA damage and restores antioxidant enzymes in rat hepatocarcinogenesis induced by diethylnitrosamine and promoted by phenobarbital.
作者信息
Banakar Mahendrakumar Chandrasekharappa, Paramasivan Suresh Kanna, Chattopadhyay Mitali Basu, Datta Subrata, Chakraborty Prabir, Chatterjee Malay, Kannan Kalaiselvi, Thygarajan Elayaraja
机构信息
Division of Biochemistry, Department of Pharmaceutical Technology, Jadavpur University, Kolkata-700032, India.
出版信息
World J Gastroenterol. 2004 May 1;10(9):1268-75. doi: 10.3748/wjg.v10.i9.1268.
AIM
To investigate the chemopreventive effects of 1alpha, 25-dihydroxyvitamin D(3) in diethylnitrosamine induced, phenobarbital promoted rat hepatocarcinogenesis.
METHODS
The rats were randomly divided into 6 different groups (A-F). Groups A, C and E rats received a single intraperitoneal (i.p.) injection of diethylnitrosamine (DEN) at a dose of 200 mg/kg body mass in 9 g/L NaCl solution at 4 wk of age, while group B served as normal vehicle control received normal saline once. After a brief recovery of 2 wk, all the DEN treated rats were given phenobarbital (PB) at 0.5 g/L daily in the basal diet till wk 20. Group A was DEN control. Treatment of 1alpha, 25-(OH)2D3 in group C was started 4 wk prior to DEN injection and continued thereafter till wk 20 at a dose of 0.3 microg/100 microL propylene glycol per one single dose (os) twice a week. Group E received the treatment of 1alpha, 25-(OH)2D3 at the same dose mentioned as above for 15 wk. The rats in group D and F received 1alpha, 25-(OH)2D3 alone as in group C without DEN injection.
RESULTS
The comet assay showed statistically higher mean values for length to width ratios (L: W) of DNA mass and tailed cells (P<0.01; P<0.01 respectively) in DEN treated rats as compared to their normal controls. Continuous supplementation of 1alpha, 25-dihydroxyvitaminD2 showed a significant (P<0.01) decrease in L:W ratio of DNA mass tailed cells. Furthermore, 1alpha, 25-(OH)2D3 supplementations elevated the super oxide dismutase (SOD) activity, hepatic malondialdehyde (MDA) level, reduced glutathione (GSH) and glutathione S-transferase (GST) activity (P<0.01, P<0.05, P<0.05 and P<0.05 respectively). As an endpoint marker histological changes were observed to establish the chemopreventive effects of 1alpha, 25-dihydroxyvitaminD2.
CONCLUSION
Supplementations of 1alpha, 25-(OH)2D3 has a marked protection against hepatic nodulogenesis, antioxidant enzymes and DNA damages in DEN induced rat hepatocarcinogenesis promoted by phenobarbital.
目的
研究1α,25 - 二羟基维生素D(3)对二乙基亚硝胺诱导、苯巴比妥促进的大鼠肝癌发生的化学预防作用。
方法
将大鼠随机分为6个不同组（A - F）。A、C和E组大鼠在4周龄时腹腔注射一次二乙基亚硝胺（DEN），剂量为200 mg/kg体重，溶于9 g/L氯化钠溶液中，而B组作为正常载体对照，仅接受一次生理盐水注射。短暂恢复2周后，所有接受DEN处理的大鼠在基础饮食中每日给予0.5 g/L苯巴比妥（PB），直至第20周。A组为DEN对照组。C组在注射DEN前4周开始给予1α,25 - (OH)2D3治疗，并持续至第20周，剂量为每单剂量0.3 μg/100 μL丙二醇，每周两次。E组以上述相同剂量接受1α,25 - (OH)2D3治疗15周。D组和F组大鼠单独接受与C组相同剂量的1α,25 - (OH)2D3，不注射DEN。
结果
彗星试验显示，与正常对照组相比，DEN处理的大鼠中DNA质量的长宽比（L:W）和拖尾细胞的平均值在统计学上显著更高（分别为P<0.01；P<0.01）。持续补充1α,25 - 二羟基维生素D2显示DNA质量拖尾细胞的L:W比显著降低（P<0.01）。此外，补充1α,25 - (OH)2D3可提高超氧化物歧化酶（SOD）活性、肝脏丙二醛（MDA）水平、还原型谷胱甘肽（GSH）和谷胱甘肽S - 转移酶（GST）活性（分别为P<0.01、P<0.05、P<0.05和P<0.05）。作为终点标志物，观察组织学变化以确定1α,25 - 二羟基维生素D2的化学预防作用。
结论
补充1α,25 - (OH)2D3对苯巴比妥促进的二乙基亚硝胺诱导的大鼠肝癌发生中的肝脏结节形成、抗氧化酶和DNA损伤具有显著的保护作用。
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