Gangar Subhash Chander, Sandhir Rajat, Rai Durg Vijay, Koul Ashwani
Department of Biophysics, Basic Medical Sciences Block, Panjab University, Chandigarh 160014, India.
Phytother Res. 2006 Oct;20(10):889-95. doi: 10.1002/ptr.1967.
In the present investigation, the effects of aqueous Azadirachta indica leaf extract (AAILE) on (3)H-benzo(a)pyrene-DNA [(3)H-B(a)P-DNA] adduct formation, the status of biotransformation enzymes and reduced glutathione (GSH) content were evaluated in the forestomach and liver of Balb/c mice. Two weeks of AAILE treatment reduced the (3)H-B(a)P-DNA adduct levels by 31.6% in forestomach tissue. Similarly, (3)H-B(a)P-DNA adduct levels were decreased by 34.7% in the liver of AAILE treated mice compared with their control counterparts. After AAILE treatment, the cytochrome P450 content decreased, whereas the GSH content increased significantly in the hepatic tissue. In the forestomach as well as in the liver, the cytochrome b5 content declined, whereas an increase in glutathione-S-transferase (GST) activity was observed in both tissues. These observations suggested that AAILE may have reduced the metabolic activation of (3)H-B(a)P with enhanced detoxification of its active metabolites, hence the observed decrease in the levels of (3)H-B(a)P-DNA adducts. These molecular and biochemical modulations observed at the initiation phase of carcinogenesis seems to be significant and could be correlated with the chemopreventive effects of A. indica against B(a)P induced forestomach tumorigenesis.
在本研究中，评估了印度楝叶水提取物（AAILE）对Balb/c小鼠前胃和肝脏中³H-苯并(a)芘-DNA（³H-B(a)P-DNA）加合物形成、生物转化酶状态和还原型谷胱甘肽（GSH）含量的影响。两周的AAILE处理使前胃组织中³H-B(a)P-DNA加合物水平降低了31.6%。同样，与对照小鼠相比，经AAILE处理的小鼠肝脏中³H-B(a)P-DNA加合物水平降低了34.7%。AAILE处理后，肝脏组织中细胞色素P450含量降低，而GSH含量显著增加。在前胃和肝脏中，细胞色素b5含量均下降，而两个组织中谷胱甘肽-S-转移酶（GST）活性均升高。这些观察结果表明，AAILE可能降低了³H-B(a)P的代谢活化，并增强了其活性代谢物的解毒作用，因此观察到³H-B(a)P-DNA加合物水平降低。在致癌作用起始阶段观察到的这些分子和生化调节似乎具有重要意义，并且可能与印度楝对B(a)P诱导的前胃癌发生的化学预防作用相关。
