الفهرس 
Aim of the workOnly 14 pages are availabe for public view
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Abstract
Hepatocellular Carcinoma (HCC), Also Called Malignant Hepatoma, Is The Most Common Type Of Liver Cancer. The Development Of Liver Cancer Occurs In A Stepwise Fashion With Frank Malignancy Resulting Once A Sufficient Number Of Oncogenes Are Activated And/Or Tumor Genes Are Inactivated. chronic Inflammation Of The Liver And Subsequent Cirrhosis Which Are Highly Correlated With Hepatitis B And C Viruses’ Infection And Alcoholic Liver Diseases Are The Strongest Risk Factors, Also Obesity And Related Metabolic Abnormalities (Such As Diabetes) Raise The Risk Factor Of HCC.
Only Surgical Resection And Liver Transplantation Are Curative Therapies. They Are In Only 30% Of The Patients, Namely Those Diagnosed With Small Tumor Burden. Systemic Chemotherapy Lacks Efficacy For HCC And There Is No Standard Treatment For Patients With Non-Resectable HCC, So Treatment Options And Prognosis Are Dependent On Many Factors But Especially On Tumor Size, Staging, And Extent Of Liver Injury. Tumor Grade Is Also Important; High-Grade Tumors Will Have A Poor Prognosis, While Low-Grade Tumors May Go Unnoticed For Many Years, As Is The Case In Many Other Organs.
The Uses Of Drugs Inducing Apoptosis Of Tumor Cells And Antioxidant Drugs Which Have Protective Effects Against Many Mitochondrial Toxic Agents Could Minimize The Harmful Effects Of HCC In Hepatic Cells. Hence, Our Study Was Designed To Investigate The Possible Therapeutic Effects Of Arsenic Trioxide (As₂O₃) And L-Carnitine Against Induced Hepatocellular Carcinoma In Rats.
To Fulfill This Goal The Study Has Been Applied As Follows:
Fifty Male Wistar Albino Rats Were Divided Into Five Groups With 10 Animals In Each group As Follows:
group I, This group Served As Negative Control group And Received Only Sterile Saline.
The Other Four Groups (from 2nd To 5th Group) Were Given A Single IP Injection Of Diethylnitrosamine (DENA) (200 Mg/Kg B.Wt.) Then After Two Weeks Received A Weekly SC. Injection Of Carbon Tetrachloride Ccl4 (3 Ml/Kg B.Wt.) For Six Consecutive Weeks.
group II, This group Received DENA Followed By Ccl4 And Served As Control Positive group (Hepatocellular Carcinoma Group).
group III, Rats Were Treated With Standard Drug Cisplatin (5 Mg/Kg, IP) For Four Weeks.
Groups IV, This group Received As₂O₃ (1mg/Kg/Day, IP). After Two Weeks, Administration Was Changed To Twice A Week And The Total Time Of Drug Administration Was Four Weeks.
Groups V, Rats Received L-Carnitine (1g/Kg/ Day, PO) For Four Weeks.
At The End Of The Experiment, Blood Samples Were Withdrawn from The Retro-Orbital Venous Plexus Of Rats, And Then The Liver Were Dissected Out. Both Serum And Tissue Were Used For Biochemical And Histological Studies.
Liver Function Biomarkers [Serum Alanine Transaminase (ALT), Aspartate Transaminase (AST), Alkaline Phosphatase (ALP), Total Bilirubin (T.Bil), Albumin, And Total Protein)]; Tumor Marker [Serum Alpha-Fetoprotein (AFP)] And Oxidative Stress Biomarkers [Hepatic Malondialdhyde (MDA), Glutathione Reduced (GSH) And Superoxide Dismutase (SOD)] Were Investigated. Histopathology And Immuno-Histochemistry P53 Of The Obtained Samples Were Also Examined.
The Obtained Results Revealed That, The Hepatocellular Carcinoma group Showed:
- Significant Increase In ALT, AST, T.Bil And ALP Levels.
- No Significant Change In Serum Albumin And Total Protein Levels In Comparison With Negative Control Group.
- Significant Increase In AFP Level As Compared To Negative Control Group.
- Significant Elevation Of Hepatic MDA Level.
- Significant Reductions Of Hepatic GSH As Compared To Negative Control Group.
- Significant Reductions Of Hepatic SOD Levels As Compared To Negative Control Group.
- Morphologically Hepatocellular Carcinoma group Showed Multifocal, Widely Distributed Nodules Of Variable Size And Shapes Which Embedded In Hepatic Parenchyma.
- Immunohistochemistry Study Of P53 Hepatocellular Carcinoma group Showed Very Strong Immunostained As Compared To Negative Control group Which Showed Very Weak Immunostained.
Cisplatin Treated group Showed:
- Significant Decrease In ALT, AST, T.Bil And ALP Levels.
- No Significant Change In Serum Albumin And Total Protein Levels In Comparison With Negative Control group And HCC Group.
- No Significant Decrease In Tumor Marker AFP Level As It Is Not Always Reflecting HCC Condition So We Don ҆T Depend On It.
- Significant Reduction Of Hepatic MDA Level When Compared To HCC Group.
- No Significant Change In Hepatic GSH Level When Compared To HCC Group.
- Significant Elevation Of Hepatic SOD Level When Compared To HCC Group.
- Morphologically Cisplatin group Showed Improvement In Histopathological Findings Through The Reduction Of Mitotic Figures With Clear Pleomorphism.
- Immunohistochemistry Study Of P53 Cisplatin group Showed Positive Stain In Few Numbers Of Hepatocytes Nuclei That Mean Fewer P53 Tumor Protein As Compared To HCC Group.
Arsenic Trioxide Treated group Showed:
- Significant Decreased In Liver Enzymes ALT, AST, ALP And T.Bil Levels As Compared To HCC Group.
- No Significant Change In Serum Albumin And Total Protein Levels In Comparison With Negative Control group And HCC Group.
- No Significant Decrease In Tumor Marker AFP Level As It Is Not Always Reflecting HCC Condition So We Don ҆T Depend On It.
- Significant Reduction Of Hepatic MDA Level When Compared To HCC Group.
- No Significant Change In GSH Level When Compared To HCC Group.
- Significant Elevation Of Hepatic SOD Level When Compared To HCC Group.
- Morphologically, We Can Find Improvement In Histopathology (Shape Of Cells).
- Immunohistochemistry (Decrease In Number Of Cells Contain P53 Gene) As Compared To Hepatocellular Carcinoma group And Cisplatin Group.
L-Carnitine Treated group Showed:
- Significant Decreased In Liver Enzymes ALT, AST, ALP And T.Bil Levels When Compared To HCC Group.
- No Significant Change In Serum Albumin And Total Protein Levels In Comparison With Negative Control group And HCC Group.
- No Significant Decrease In Tumor Marker AFP Level.
- No Significant Change In GSH Level When Compared To HCC Group.
- Significant Reduction Of Hepatic MDA Level When Compared To HCC Group.
- Significant Elevation Of Hepatic SOD Level When Compared To HCC Group.
- Morphologically, We Can Find Improvement In Histopathology (Shape Of Cells).
- Immunohistochemistry (Decrease In Number Of Cells Contain P53 Gene) As Compared To Hepatocellular Carcinoma group And Cisplatin Group.
Finally, It Could Be Concluded from This Study:
Treatment Of HCC With As₂O₃ Or L-Carnitine Showed Improvement In The Morphology Of The Cell And Liver Enzymes In Hepatocellular Affected Rats, Due To Apoptotic Effect Of As₂O₃ In Addition To Antioxidant Effect Of L-Carnitine As Well As Treatment With As₂O₃ Is Better Than L-Carnitine As Compared To Cisplatin.