الفهرس | Only 14 pages are availabe for public view |
Abstract Given the lack of progress in curing metastatic epithelial cancers, there is intense interest in, and a sound scientific rationale for, pursuing strategies to prevent cancer. However, although several clinical trials have shown efficacy in cancer prevention, few have resulted in changes to medical practice, and some trials have even shown harm. Recent experiences with serious side effects identified in cancer prevention trials underscore the need to re-evaluate our approach to clinical chemopreventive drug development. The present study was done to evaluate the protective effect of Ginkgo biloba extract and / or low dose gamma irradiation on ferric nitrilotriacetate induced hepatic and renal carcinogenesis in rats. For this purpose eighty adult male albino (120-150 g) rats were randomly distributed into 8 groups (each of 10 rats) as following : group 1: Untreated control group. group 2: Animals of this group received pretreatment with ginkgo biloba extract (100 mg / kg / day ) 3 times per week for 21 weeks. Summary 153 group 3: Animals of this group exposed to γ-radiation (50 cGy per week) for 19 weeks . group 4: Animals of this group intraperitoneally injected with Fe-NTA (9 mg Fe/kg body wt) twice a week for 20 weeks. group 5: Animals of this group received pretreatment with ginkgo biloba extract as described in group (2) and exposed to γ-radiation as described in group (3). group 6: Animals of this group received pretreatment with ginkgo biloba extract as described in group (2) and intraperitoneally injected with Fe-NTA as described in group (4). group 7: Animals of this group intraperitoneally injected with Fe-NTA as described in group (4) and exposed to γ- radiation as described in group (3). group 8: Animals of this group received pretreatment with ginkgo biloba extract as described in group (2), intraperitoneally injected with Fe-NTA as described in group (4) and exposed to γ-radiation as described in group (3). At the end of the experiment blood, liver and kidney samples were collected for biochemical determinations and histopathological observations. Summary 154 The results were statistically analyzed and represented in tables and figures. The gained results were summarized as following : ALT and AST activities were elevated in Fe- NTA treated rats as well as BUN and creatinine levels which reflect the hepatic and renal damage that have been induced in these rats. Fe-NTA injected groups showed a marked depletion in GSH content, GPx, SOD and catalase activities in blood, liver and kidney with a significant increase in lipid peroxide and NO levels in blood, liver and kidney compared to the control group which indicate the highly oxidized state of Fe-NTA treated rats. Fe-NTA induced notable ROS, which played a protective role in apoptosis by inhibiting Caspase-3 activation in liver and kidney tissues whole body γ-radiation exposure of rats caused severe degenerative changes in liver and kidney tissues resulted in a marked elevation in ALT and AST activities and a significant increase in creatinine and urea levels. Summary 155 a considerable decrease in the levels of GSH, GSHPX , catalase and SOD was observed in γ- irradiated groups with a distinct increase in LPx level which illustrate the damaging effect of low dose γ- irradiation. Pretreatment with G. biloba extract led to a marked decrease in ALT, AST, creatinine and BUN levels compared to the Fe-NTA treated rats. Pretreatment of Fe-NTA treated rats with G. biloba extract increased GSH content, Gpx, SOD and catalase activities in blood , liver and kidney of these rats with depletion in lipid peroxide and NO levels. GB Treatment caused a marked increase in levels of liver and kidney Caspase-3 restoring its anticarcinogenic effect by activation of apoptosis. In conclusion, the results of the present study indicate that low dose γ- irradiation produced a cytotoxic damaging effect in blood, liver and kidney of irradiated rats which is conversed with the expected effect. Simultaneous treatment with G. biloba extract protects the liver and the kidney against Fe-NTA and / or γ- irradiation induced hepatic and renal cytotoxicity . These effects are mainly attributable to the polyvalent actions of the Summary 156 flavonoid constituents of GB, including their ability to scavenge free radicals and to modulate signal transduction pathways |