الفهرس 
IntroductionOnly 14 pages are availabe for public view
 |  | from | 233 |  |  |
| | | from | 233 | | |
Abstract
Summary
Liver cancer is ranked in the top 10 human cancers worldwide and among the top five of cancers in terms of mortality. Many studies suggested that the risk factors related to liver cancer are alcohol abuse, smoking, and exposure to aflatoxins, sex, ethnicity, as well as infection by hepatitis B (HBV) and C viruses (HCV). The combination therapy was shown to induce apoptosis in a synergistic fashion. It is the basic strategy to increase response, tolerability and decrease resistance. The advantages, which attributed to combination chemotherapy include improved patient compliance because it reduced the number of administrations, appearance of additive or synergistic interaction effects, ability to overcome drug resistance and reduction of drug dose with consequent diminishing of toxicity to healthy tissues.
Nanotechnology is the treatment of individual atoms, molecules, or compounds into structures to produce materials and devices with special properties by reducing the size of large structures to smallest structure. Nanomedicine is developing multifunctional constructs of drugs to fight cancer cells.
In the present study the complex was prepared by suspending Ga2O3 nanoparticles in 90 gm Cu-CTAB dissolved
Summery 154
in 100 ml distilled water by using ultrasonication for 30 minutes. The chemical structure of the prepared complex was evident by TEM
Different concentrations of Cu-CTAB, GaO-NPs and complex (Cu-CTAB+GaO-NPs) suspension were prepared. The
was detected for each, using crystal violet cytotoxicity assay, against hepatocellular carcinoma human cell line (HepG-2). The
values were 11.07, 360 and 0.2 μg/ml respectively.
For the in vivo application, a hepatocellular carcinoma animal model was induced using Diethylnitrosamine (DEN) as a potent carcinogen. Eighty Wister male rats were divided into eight groups (10 rats of each) and classified as follow:
group I (Normal control): Untreated control group.
group II (Cu-CTAB): Rats received 6.5 mg/ kg body weight of Cu-CTAB (Badawi et al., 2012) orally five times per week for 4 weeks.
group III (GaO-NPs): Rats orally administrated GaO-NPs (3.3 mg/ kg b.w. five times per week for four weeks by intragastric gavage.
group IV (Complex) (Cu-CTAB+GaO-NPs): Rats received 16.3 mg/ kg b.w. of complex orally (five times per week) for 4 weeks.
Summery 155
group V (DEN): Rats received 20 mg/kg b. w. of DEN orally (five times per week for 6 weeks) and left alive for 4 weeks. group VI (DEN+Cu-CTAB): Rats received DEN as in-group V, then were administrated the Cu-CTAB orally five times per week for 4 weeks as in-group II.
group (VII) (DEN+GaO-NPs): Rats received DEN as in-group V, then were administrated the GaO-NPs orally five times per week for 4 weeks as in-group III.
group VIII (DEN+Complex): After rats received DEN as in-group V, then were administrated the complex orally five times per week for 4 weeks. At the end of the treatment period, rats were sacrificed; blood and liver tissue samples were collected for the biochemical and histopathological examinations. The biochemical investigation including; (AST, ALT, total protein, iron, Arginase, α-L-Fucosidase, AFP, MDA, SOD , TGF-1β, and capase-3).
Results obtained from the current study showed that male rats treated with DEN were capable of inducing oxidative stress by ROS generation, They were manifested by elevated MDA level accompanied by depleted antioxidant defense (such as SOD activities). A significant decrease in caspase-3 activity attributed to over production of caspase inhibitors by cancer cells and a significant elevation in TFGβ-1, AFP, α-L-
Summery 156
fucosidase and arginase in this group may indicate that the proliferation rate of cancerous cells increased. A significant depression in serum iron content in this group indicates the ability of the tumors to uptake much more iron for their enhanced proliferation. Furthermore, marked elevations in ALT and AST enzymes with decrease in serum total protein concentration, displayed by this group, could be illustrated by the effect of oxidative stress on the integrity of mitochondrial membranes causing damage liver tissues. Administration of (Cu-CTAB) alone and/or combined with (GaO-NPs) in induced-tumor groups decrease of liver enzymes ALT and AST with increase in total protein, which could be illustrated by the effect of treatment on integrity of mitochondrial membranes. This treatment improved some of antioxidant enzyme activities in blood such as SOD and depletion of lipid peroxidation marker (MDA) and increase caspase-3 level in serum during cancer formation to induce apoptosis. Due to the treatment potential as inhibitors of tumor growth, there is a significant decrease in tumor markers level (AFP, α-l-Fucosidase and arginase).
Conclusion & Recommendation 157
Conclusion
As a conclusion, from the current results found that both Cu-CTAB alone and/or combined with GaO-NPs exerted cytotoxic effects against DEN-induced HCC, which would in turn, speculate a possible therapeutic role of the novel Cu-CTAB+GaO-NPs compound. Else more, it is worth mentioning once again that the effect of the applied combined supplementation of Cu-CTAB with GaO-NPs didn’t meet our expectations as it caused hepatotoxicity and the toxicity induced by GaO-NPs was less than Cu-CTAB and complex.
Recommendations
The present study provides the rationale for the use of gallium oxide nano-particles alone in further preclinical models for hepatocellular carcinoma therapy. This can be used especially in early stages of the disease, or together with a suitable compound with antioxidant property, as a backup to fulfill body demands for antioxidant defense system, in order to cope with the pro-oxidant activity of the gallium oxide.