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Abstract Hepatocellular carcinoma (HCC) is a major health problem worldwide, with an estimated incidence ranging between 500,000 and 1000,000 new cases annually. It is the fifth most common cancer in the world, and the third most common cause of cancer-related death. The purpose of our thesis was in two directions, The first one was to study the hepatoprotective and anticancer role of aqueous olive leaf extract as a herbal medicine for modulating the metabolic disorders occurring in HCC showing its therapeutic value in contrast to 5-FU which is a well known cheap anticancer with many side effects hoping both to potentiate its anticancer activity and decrease its side effects. the second one was to explore new or highly related rapid and sensitive markers for early diagnosis of hepatocellular carcinoma such as (acetyl CoA synthase enzyme, lipoprotein lipase enzyme and glycosaminoglycans) as most of known tumor markers appear at late stages of the disease, that was monitored along with alpha-fetoprotein (AFP) which is the most common tumor marker for hepatocellular carcinoma in a trial to raise its sensitivity and specifity. 64 male wister rats were used and classified into 8 groups each of 8 rats. They were divided as the following: Group I: Untreated normal healthy group (normal control group). Group II: Treated with 5-fluorouracil (5-FU) (75mg/kg/ I.P.) once weekly for 3 successive weeks. Group III: Treated with aqueous olive leaf extract (500mg/kg) once daily for continuous 28 days. Group IV: Treated with olive leaf extract and 5-FU for periods as mentioned above for each drug. Group V: Received daily doses of trichloroacetic acid (TCA) (500mg/kg/day) for five days. Group VI: Received daily doses of trichloroacetic acid (TCA) for 5 days then treated with 5-FU for 3 weeks as stated above. Group VII: Received daily doses of trichloroacetic acid (TCA) for 5 days then treated with olive leaf extract. Group VIII: Received daily doses of trichloroacetic acid (TCA) for 5 days then treated with 5-FU and olive leaf extract together. Samples of serum and plasma (collected on non-EDTA and EDTA containing tubes) were stored at –80 ºC, and then we measured the following parameters: Serum alanine aminotransferase (ALT) activity, serum aspartate aminotransferase (AST) activity, serum alkaline phosphatase (ALP) activity, plasma triglycerides (TG) (Triacylglycerol) level, serum total glycosaminoglycans (GAGs) level, plasma total bilirubin level, serum alpha fetoprotein (AFP) level, serum acetyl coA synthase (ACAS) activity , serum lipoprotein lipase activity, histopathological findings of liver sections were also examined. from our results, the data showed that treatment with TCA induced a significant increase in serum alanine aminotransferase (ALT), aspartate aminotransferase (AST) and alkaline phosphatase (ALP) activities, also in plasma total bilirubin, triglycerides, serum total glycosaminoglycans, alpha-fetoprotein, and acetyl CoA synthase (ACAS) activity. Also, it induced a significant reduction in serum lipoprotein lipase activity (LPL). The histopathological results showed that damaged neoplastic hepatic tissue by TCA was treated and reversed towards normal cellular architecture by treatment with AOLE and 5-FU. In the present study, it could be noticed that the treatment with AOLE specially in combination with 5-FU produced a pronounced improvements in most of the studied parameters up to or towards the normal range which could be explained on the basis of improvement the liver functions and the protection against the oxidative damage that may be involved in cancer induction. Finally, our study concluded that aqueous olive leaf extract has hepatoprotective and anticancer properties especially in combination with 5-FU. Also GAGs level, LPL and ACAS activities can be added as new markers for early diagnosis of hepatocellular carcinoma. Finally chlorination of drinking water is a critical process and chlorination byproducts as TCA are so harmful to human so strict measures have to be taken to control this process and find more safe water disinfection process. |