Agha A M, El-Fattah A A, Al-Zuhair H H, Al-Rikabi A C
Dept. of Pharmacology, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia.
J Exp Clin Cancer Res. 2001 Mar;20(1):39-50.
Ginkgo biloba extract (EGb) is a natural product that possesses antioxidant and anticlastogenic properties. The current study was conducted to investigate the effect of EGb on benzo(a)pyrene (BP)-induced forestomach neoplasia, and to explore its possible beneficial effects against doxorubicin (Dox)-induced cardiotoxicity. Tumor was induced in female Swiss albino mice by oral administration of 1 mg BP, twice weekly for four weeks. EGb was given, at a daily oral dose of 150 mg kg(-1), two weeks before and during BP administration. Dox was given ip at a dose of 1.5 mg kg(-1), once weekly, for four weeks, during BP administration. EGb and Dox were given as combined or monotherapies. Results of the present investigation revealed that EGb blunted forestomach tumor multiplicity, as compared to control tumor bearing group. It also exhibited high activity to induce cytosolic glutathione S-transferase and glucose-6-phosphate dehydrogenase (G6PDH) in liver, as well as replenished hepatic glutathione that have been inhibited or depleted by tumorigenesis. Furthermore, it normalized nitric oxide (NO) serum level, without any observed alteration in neither the activity of liver microsomal NADPH-cytochrome P-450 reductase nor serum level of tumor necrosis factor-alpha (TNFalpha). Similar results have been obtained with Dox, but it failed to affect G6PDH activity, while increased serum TNFalpha and NO levels. The combined therapy did not add further to the anticarcinogenic effect of Dox, however it succeeded in ameliorating the deleterious effects of Dox on the heart; as evidenced by the reduction of cardiac lipoperoxidation, with modulation of Dox-induced pathological changes. Therefore, EGb confers a beneficial chemopreventive effect against BP-induced gastric carcinogenesis in mice, and possesses a salutary ameliorating potential on the cardiotoxic effects of Dox.
银杏叶提取物（EGb）是一种具有抗氧化和抗致突变特性的天然产物。本研究旨在探讨EGb对苯并(a)芘（BP）诱导的前胃肿瘤形成的影响，并探索其对阿霉素（Dox）诱导的心脏毒性可能的有益作用。通过每周两次口服1 mg BP，持续四周，诱导雌性瑞士白化小鼠发生肿瘤。在给予BP前两周及给药期间，每天口服给予EGb，剂量为150 mg/kg(-1)。在给予BP期间，每周一次腹腔注射给予Dox，剂量为1.5 mg/kg(-1)，持续四周。EGb和Dox以联合或单一疗法给药。本研究结果显示，与对照肿瘤组相比，EGb可降低前胃肿瘤的多发性。它还表现出在肝脏中诱导胞质谷胱甘肽S-转移酶和葡萄糖-6-磷酸脱氢酶（G6PDH）的高活性，以及补充因肿瘤发生而被抑制或消耗的肝脏谷胱甘肽。此外，它使一氧化氮（NO）血清水平正常化，而未观察到肝脏微粒体NADPH-细胞色素P-450还原酶活性或肿瘤坏死因子-α（TNFα）血清水平有任何改变。Dox也得到了类似的结果，但它未能影响G6PDH活性，同时增加了血清TNFα和NO水平。联合疗法并未进一步增强Dox的抗癌作用，然而它成功地改善了Dox对心脏的有害影响；心脏脂质过氧化的减少以及Dox诱导的病理变化的调节证明了这一点。因此，EGb对小鼠BP诱导的胃癌发生具有有益的化学预防作用，并且对Dox的心脏毒性作用具有有益的改善潜力。
