الفهرس 
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Abstract
The present study is an experimental trial to assess the hepato-toxic effect of iron and to investigate the effect of antioxidant plant extract as chemo-protective and chemotherapeutic agent taking the advances of being cheap, available and safe alternative to the available chemotherapeutic drugs, avoiding their various side effects.
The goal of the present work was to inveatigate the possible protective and treatment mechanisms by which antioxidant plant extract (Piper longum extract) and cytotoxic agent (methotrexate) counteract iron-induced HCC. The present work performed both in-vivo and in-vitro experiments to study the antioxidant and anticancer activities of these drugs against iron-induced HCC. The iron overload model used in this study was through Intraperitoneal injection of Fe-NTA (an iron generator) for 60 days.
The in-vivo and in-vitro studies included the following parameters:
1- Assessment of iron content:
a). Change in serum iron, TIBC,UIBC and transferrin levels.
2- Assessment of hepato-toxicity:
a). Liver enzymes: AST and ALT.
3- Assessment of oxidative stress markers:
a). Antioxidant enzymes: GSH content, SOD, catalase, GSH peroxidase, GSH reductase and GSH-s-transferase activities.
b). Oxidative particles: lipid peroxidation, H2O2 and conjugated diene levels.
4- Assessment of different cell characters:
a). DNA fragmentation.
b). Characterization of cell death (apoptosis).
c). Histopathological examination of liver cells.
5- Assessment of some adverse effects:
a). Lung metastasis.
b). Mortality rate.
6- In-vitro experiments:
a). Antioxidant activity (Scavenging of DPPH radicals).
b). Anti-tumor activity (Hep-G2, HL-84 and HCT-116 cell lines).<The results obtained can be summarized as follow:
1. Effect of Fe-NTA (15 mg/kg) as iron generator:
a. Intraperitoneal injection of Fe-NTA (15 mg/kg) induced a state of iron overload, showed by the significant increase in serum iron, TIBC, UIBC and transferrin levels in adult female rats when compared with normal rats.
b. Effect of Fe-NTA (15 mg/kg) on liver function parameters was shown by the significant increase in both AST and ALT activities in adult female rats when compared with normal rats.
c. It was found that Fe-NTA (15 mg/kg) caused imbalance in redox system which was evidenced by the significant reduction in GSH content and antioxidant enzymes; SOD, catalase, GSH peroxidase, GSH reductase and GSH-s-transferase and the significant increase in oxidative particles; lipid peroxidation, H2O2 and conjugated diene levels when compared with normal rats.
d. Fe-NTA (15 mg/kg) caused significant increase in DNA fragmentation in liver cells when compared with normal group.