الفهرس 
I. INTRODUCTIONOnly 14 pages are availabe for public view
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Abstract
Liver is a vital organ present in all vertebrates including human. Reasons for this include the following: 1) this organ plays numerous important metabolic functions, such the regulation of carbohydrate metabolism, the production of plasma proteins, and the synthesis of bile, 2) nutrients derived from intestinal absorption are stored in hepatocytes and released for further catabolism by other tissues, 3) the yolk protein, vitellogenin, destined for incorporation into the oocyte, is synthesized entirely within the liver, 4) it is the major site of the cytochrome P450-mediated, mixed-function oxidase system, and, while this system inactivates or detoxifies some xenobiotics, it activates others to their toxic forms, and 5) bile synthesized by hepatocytes aids in the digestion of fatty acids and carries conjugated metabolites of toxicants into the intestine for excretion or intrahepatic recirculation. It that means, the liver is responsible for many critical functions within the body and should it become diseased or injured, the loss of those functions can cause significant damage to the body. There are more than a hundred kinds of liver disease, these are some of the most common fascioliasis, hepatitis, alcoholic liver disease, fatty liver disease, hereditary diseases, glbert’s syndrome, cirrhosis, liver cancer, primary biliary cirrhosis etc. Liver disease can occur through several mechanisms. A common form of liver disease is viral infection. High consumption of alcohol can lead to several forms of liver disease including alcoholic hepatitis, alcoholic fatty liver disease, cirrhosis, and liver cancer. In the earlier stages of alcoholic liver disease, fat builds up in the liver’s cells due to increased creation of triglycerides and fatty acids and a decreased ability to break down fatty acids. Progression of the disease can lead to liver inflammation from the excess fat in the liver. Scarring in the liver often occurs as the body attempts to heal and extensive scarring can lead to the development of cirrhosis in more advanced stages of the disease. Approximately 3-10% of individuals with cirrhosis develop a form of liver cancer known as hepatocellular carcinoma. Huge chemical medications are available to treat liver disease. Such modern pharmacological therapy is costly and associated with multiple side effects resulting in patient non-compliance. Thus there is a need to explore alternative therapies particularly from the natural sources as these are cost effective and possess minimal side effects. Many of authorities and academic centers of research pay more attention towards the area of natural bioactive compounds called phytochemicals (phyto is Greek for plant). It is differ from vitamins and minerals in that they have known nutritional value. Some are antioxidants, protecting against harmful cell damage from oxidation. Others perform different functions that help prevent cancer. Scientists have identified thousands of phytochemicals, including flavonoids, glucosinolates (isothiocyanates and indoles), phenolic acids, phytates, and phytoestrogens (isoflavones and lignans), in vegetables, fruits, grains, legumes, and other plant sources. A vast variety of phytochemicals that are present in the daily human diet have been found to possess substantial antimutagenic and anticarcinogenic properties (Surh, 2002). The chemopreventive effects of the majority of edible phytochemicals are often attributed to their antioxidative or anti-inflammatory activities. Besides the edible chemopreventives in vegetables, fruits, herbs, and spices, some phytochemicals in diverse plants also have other beneficial health effects such as anti-obesity, lipid-lowering, and/or antidiabetic properties. Thus, new aspects concerning the use of agro-industrial wastes/by-products for further exploitation on the production of extracts rich with bioactive compounds have gained increasing interest because these are high-value products and their recovery may be economically attractive. Although the using of such plant parts in different medicinal applications is still in debates because of potential toxicological points of view. Therefore, the objective of this study is to highlight the potential of selected plant parts extracts (Sweet violet, marjoram, onion skin and orange peel) as a source of bioactive compounds and natural and antioxidants. Also, examination of the potential for those selected plant parts individually or to work together to improve the liver injuries induced by CCl4 in vitro will be in the scope of this study. To achieve such objectives, the study protocol was designed as follow: selected plant parts, Orange ”Citrus sinensis L.” peel (OP), Sweet violet ”Viola odorata L.” blossoms (SVB), Red onion ”Allium cepa L.” skin (ROS) and Marjoram ”Origanum majorana” leaves (ML) were obtained and their different types of extracts were prepared. Antioxidant activity of selected plant parts extracts was determined and calculated in four different way, antioxidant value (AOX), antioxidant activity (AA), oxidation rate ratio (ORR) and antioxidant activity coefficient (AAC). Total phenolics of selected plant parts extracts were determined in a trial to make a correlation with their antioxidant activities (AA).Bolti fish (Tilapia nilotica) liver homogenate and human lymphocytes were prepared and used as a biological model in vitro and used for measuring of the toxic effects of CCl4. Determination of the ideal concentrations of the selected plant parts extract for applying in co-treatment with CCl4. Effect of selected plant parts methanolic extract on the cytotoxicity of CCl4 in liver cells and genotoxicity of CCl4 in lymphocytes cells. The obtained data could be summarized as follow: 1.Extractive value of selected plant parts using different organic solvents The extractive value of selected plant parts were determined by successive extraction in different solvents using a Soxhlet’s apparatus. The extractive value for selected plant parts in water and hexane was low (1.04- 2.32%) while relatively high in methanol and ethanol (2.12-7.45 %). 2. Antioxidant activity and total phenolics of selected plant parts methanolic extracts 2.1 Antioxidant activities The selected plant parts methanolic extracts showed considerable differences in antioxidant activity (AA= 51.78±6.12 to 91.38± 10.22 %). Red onion skin (ROS) and marjoram leaves (ML) extracts showed strong activity because of its high phenolic content (349.49±89.87 and 128.65±27.94 mg GAE. g-1, respectively) while orange peel (OP) and sweet violet blossoms (SVB) showed relatively low content in both antioxidant activity and the total phenolics. Red onion skin extract (ROS) recorded the lowest decreasing followed by Marjoram leaves (ML), Orange peel (OP) and Sweet violet blossoms (SVB), respectively. The values of onion skin extract (ROS) absorbance through 120 min are coming well i.e. closing the line of 50 mg /L of α-tocopherol followed by the rest plant by-product parts. These data proved the high stability of the all tested plant by-products when comparing with that more common standard α-tocopherol. 2.2 Relationship between phenolic contents and antioxidant activity The total phenolic content of the selected plant parts methanolic extracts investigated in this study varied from 33.56± 4.87349.49± 89.87 mg GAE.g-1. When all selected plant parts methanolic extracts were included in the statistical analysis, there was a positive and highly significant (r2= 0.676-0.932, p< 0.05) relationship between total phenolics and antioxidant activity. The highest value was recorded for ROS (r2= 0.932, p< 0.05) followed by OP (r2= 0.836, p< 0.05), ML (r2= 0.795, p< 0.05), and SVE (r2= 0. 676, p< 0.05), respectively. 3. Effect of selected plant parts methanolic extract on the cytotoxicity of CCl4 in liver cells as determined by different assays 3.1 Determination of the ideal concentrations of the selected plant parts extract for applying in co-treatment with CCl4 Bolti fish liver cells homogenate were incubated with serial dilutions of CCl4 alone and in co-treatment with mixture of the selected plant parts methanolic extract by different concentrations (0.25-1.0%). Neutral red (NR) assay which determined the lysosomal activity was used to make a dose response toxicity of CCl4. The data were standardized by expressing absorbance data in the presence of each mixture concentration as a percentage of that in the control medium. Such as shown in Table (1) and Figure (1), the absorbance measurements of NR assay (as % of control) were 17.51-104.78, 41.30-104.09, 50.65-107.66, 58.84-113.83 and 60.32-114.74 for the CCl4 alone and co-treatment with mixture of the selected plant parts methanolic extract by different concentrations (0.25, 0.50, 0.75 and 1.0%)., respectively. 3.2 Cytotoxicological studies The absorbance measurements of assays (as % of control) were 17.51-104.78, 32.89-109.67, 29.89-108.45, 56.76-111.67, 51.99-109.54 and 59.20-112.61 ( for NR); 22.73-106.07, 34.60-112.05, 32.36-111.24, 59.58-115.25, 57.50-113.72 and 60.32-115.75 ( for MTT); and 29. 56-110.79, 49.10-115.14, 41.98-116.47, 62.10-116.18, 57.53-112.81 and 63.07-119.11 (for CV) for the CCl4 and CCl4 plus the four selected plant parts extract OP, SVB, ROS,ML as well as their mixture, respectively. Also, data indicated that CCl4 induced many adverse cytotoxic effects including lysosomal and mitochondrial dysfunctions and cell membrane integrity of liver cells which expressed by NR, MTT and CV assays, respectively. Co-treatment of liver cell with CCl4 and the tested selected plant parts extracts as well as their mixture exhibited therapeutic effects through decreasing the all of the different cytotoxic effects. That decreasing in different cytototoxic effects was depending on the type of the plant parts applied. The highest therapeutic effect was recorded for the mixture of the selected plant parts extracts followed by ROS, ML, OP and SVB, respectively. 3.3 Studying the initial and midpoint toxicity of the selected plant parts methanolic extract towards liver homogenate of Bolti fish The initial and midpoint cytotoxicity value for CCl4 was recorded lowest values for NR, MTT and CV. Co-treatment of liver cell with CCl4 and the tested selected plant parts extracts as well as their mixture induced significantly reduction in the initial and midpoint cytotoxicity values i.e. exhibited therapeutic effects against CCl4 cytotoxicity. According to these data, the sequence of tested extracts for the different cytotoxicity assays were CCl4> CCl4+SVB> CCl4+OP > CCl4+ML > CCl4+ROS > CCl4+Mix. 4. Effect of selected plant parts methanolic extract on the immunotoxicity of CCl4 in liver cells The absorbance measurements of PA assays (as % of control) were 41.04-116.33, 54.17-119.99, 50.92-120.19, 64.65-119.09, 60.68-115.06 and 65.33-122.33for the CCl4 and CCl4 plus the four selected plant parts extract OP, SVB, ROS,ML as well as their mixture, respectively. Also, data indicated that CCl4 induced some adverse immunotoxic effects which expressed by PA assay. Co-treatment of liver cell with CCl4 and the tested selected plant parts extracts as well as their mixture exhibited therapeutic effects through decreasing the immunotoxic effects. That decreasing in mmunotoxic effects was depending on the type of the plant parts applied. The highest therapeutic effect was recorded for the mixture of the selected plant parts extracts followed by ROS, ML, OP and SVB, respectively. 5.Effect of selected plant parts methanolic extract on the genotoxicity of CCl4 by using of human lymphocyte cultures 5.1 Viability of human lymphocyte The viability of human lymphocyte exposed to CCl4 and CCl4 plus the four selected plant parts extract OP, SVB, ROS,ML as well as their mixture. The tested dilutions of CCl4, 10-7 to 10-1, decreased the human lymphocyte viability which were ranged 94.12 to 27.98% . The co-treatment of CCl4 with OP, SVB, ROS and ML as well as their mixture increased the human lymphocyte viability which ranged 96.18-43.24, 95.01-39.67, 98.67-70.14, 97.99-65.05 and 99.04-71.29%, respectively. 5.2 DNA damage detection by comet assay The percentages of normal and migrated spots of DNA of CCl4 and CCl4 plus the four selected plant parts extract OP, SVB, ROS,ML as well as their mixture. The tested dilutions of CCl4, 10-7 to 10-1, increased the percentage of total damaged spots and the normal DNA-lymphocytes (as % of control) were ranged 95.95 to 58.18%. The co-treatment of CCl4 with OP, SVB, ROS and ML as well as their mixture increased the normal DNA-lymphocytes which ranged 97.93-65.76, 96.05-65.73, 98.55-84.73, 98.3-78.45 and 99.23-89.76 %, respectively. These values were found to be highly significant (p<0.01) and dose dependent