Chemopreventive effect of Ginkgo biloba extract against benzo(a)pyrene-induced forestomach carcinogenesis in mice: amelioration of doxorubicin cardiotoxicity.
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.
Agha
A M
AM
Dept. of Pharmacology, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia.
El-Fattah
A A
AA
Al-Zuhair
H H
HH
Al-Rikabi
A C
AC
D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000627:therapeutic use*; D000975:Antioxidants / Q000627:therapeutic use; D001564:Benzo(a)pyrene / Q000037:antagonists & inhibitors / Q000633:toxicity*; D002273:Carcinogens / Q000633:toxicity; D004317:Doxorubicin / Q000627:therapeutic use* / Q000633:toxicity; D005260:Female; D005419:Flavonoids / Q000627:therapeutic use*; D020441:Ginkgo biloba; D005978:Glutathione / Q000378:metabolism; D006321:Heart / Q000187:drug effects*; D015227:Lipid Peroxidation / Q000187:drug effects; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D051379:Mice; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D010936:Plant Extracts; D013274:Stomach Neoplasms / Q000139:chemically induced / Q000188:drug therapy / Q000473:pathology / Q000517:prevention & control*; D000096983:Ginkgo Extract
D000972:Antineoplastic Agents, Phytogenic; D000975:Antioxidants; D001564:Benzo(a)pyrene; D002273:Carcinogens; D004317:Doxorubicin; D005419:Flavonoids; D005978:Glutathione; D010936:Plant Extracts; C063170:Ginkgo biloba extract; D000096983:Ginkgo Extract