Bhattacharjee Nandini, Banerjee Pathikrit, Anisur Rahman Khuda-Bukhsh Anisur
Cytogenetics and Molecular Biology Laboratory, Department of Zoology, University of Kalyani, Kalyani 741 235, India.
Indian J Biochem Biophys. 2009 Aug;46(4):307-18.
The study was undertaken to examine whether Carcinosin-200 (Car-200) could provide additional ameliorative effect, if used intermittently with Natrum sulphuricum-30 (Nat Sulph-30) against hepatocarcinogenesis induced by chronic feeding of p-dimethylaminoazobenzene (p-DAB) and phenobarbital (PB) in mice (Mus mnusculus). Mice were randomly divided into seven sub-groups: (i) normal untreated; (ii) normal + succussed alcohol; (iii) p-DAB (0.06%) + PB (0.05%); (iv) p-DAB + PB + succussed alcohol, (v) p-DAB + PB + Nat Sulph-30, (vi) p-DAB + PB + Car-200, and (vii) p-DAB + PB + Nat Sulph-30 + Car-200. They were sacrificed at 30, 60, 90 and 120 days for assessment of genotoxicity through cytogenetical end-points like chromosome aberrations, micronuclei, mitotic index and sperm head anomaly and cytotoxicity through assay of widely accepted biomarkers and pathophysiological parameters. Additionally, electron microscopic studies and gelatin zymography for matrix metalloproteinases (MMPs) were conducted in liver at 90 and 120 days. Results showed that administration of Nat Sulph-30 alone and in combination with Car-200 reduced the liver tumors with positive ultrastructural changes and in MMPs expression, genotoxic parameters, lipid peroxidation, gamma-glutamyl transferase, lactate dehydrogenase, blood glucose, bilirubin, creatinine, urea and increased GSH, glucose-6-phosphate dehydrogenasc, superoxide dismutase, catalase, glutathione reductase activities and hemoglobin, cholesterol, and albumin levels. Thus, intermittent use of Car-200 along with Nat Sulph-30 yielded additional benefit against genotoxicity, cytotoxicity, hepatotoxicity and oxidative stress induced by the carcinogens during hepatocarcinogenesis.
本研究旨在探讨癌菌素-200(Car-200)与硫酸钠盐-30(Nat Sulph-30)间歇联合使用时,是否能对小鼠(小家鼠)长期喂食对二甲氨基偶氮苯(p-DAB)和苯巴比妥(PB)诱导的肝癌发生提供额外的改善作用。小鼠被随机分为七个亚组:(i)正常未处理组;(ii)正常+振荡酒精组;(iii)p-DAB(0.06%)+PB(0.05%)组;(iv)p-DAB+PB+振荡酒精组;(v)p-DAB+PB+Nat Sulph-30组;(vi)p-DAB+PB+Car-200组;(vii)p-DAB+PB+Nat Sulph-30+Car-200组。在第30、60、90和120天处死小鼠,通过染色体畸变、微核、有丝分裂指数和精子头部异常等细胞遗传学终点评估遗传毒性,并通过检测广泛接受的生物标志物和病理生理参数评估细胞毒性。此外,在第90和120天对肝脏进行电子显微镜研究和基质金属蛋白酶(MMPs)的明胶酶谱分析。结果表明,单独使用Nat Sulph-30以及与Car-200联合使用均能减少肝肿瘤,伴有超微结构的阳性变化以及MMPs表达、遗传毒性参数、脂质过氧化、γ-谷氨酰转移酶、乳酸脱氢酶、血糖、胆红素、肌酐、尿素的降低,同时谷胱甘肽(GSH)、葡萄糖-6-磷酸脱氢酶、超氧化物歧化酶、过氧化氢酶、谷胱甘肽还原酶活性以及血红蛋白、胆固醇和白蛋白水平升高。因此,在肝癌发生过程中,Car-200与Nat Sulph-30间歇联合使用对致癌物诱导的遗传毒性、细胞毒性、肝毒性和氧化应激具有额外的益处。