الفهرس 
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Abstract
Lifestyle and diet modulate metabolic syndrome and induces pathophysiological changes throughout the body. The change includes obesity, insulin resistance, hypertension, impaired glucose tolerance and dyslipidaemia and is associated with an increased risk of non alcoholic fatty liver disease and kidney dysfunction. The Egyptian diet is rich in carbohydrates such as fructose and sucrose as well as saturated fat. Combinations of fructose or sucrose and fat-rich dietary components have been used in rodents to mimic the metabolic syndrome. Sucrose content varied between 10% and 30% whereas fat content varied between 20% and 40%. Feeding on high-sucrose, high-fat diet induced abdominal fat deposition, hyperinsulinaemia, hyperglycaemia, hyperleptinaemia, oxidative stress, hepatic steatosis and increased hepatic lipogenic enzyme activities.
There are two types of adipose tissue, brown adipose tissue that functionally control of body temperature and adiposity and white adipose tissue that functions in lipid storage, storing triacylglycerides following energy excess, and mobilizing these stores during periods of nutrient deprivation. Adipose differentiation is the result of transcriptional remodelling that leads to activation of a large number of adipose-related genes like PPARγ which is highly expressed in adipocytes and plays a role in improving glucose homeostasis. Insulin resistance is usually associated with higher concentrations of TG and lower concentrations of HDL and increased inducible nitric oxide synthase which inhibit adiponectin secretion from adipocytes, causes vascular dysfunction in obesity. Moreover, both insulin resistance and hyperinsulinemia lead to endothelial dysfunction. Physical compression of both kidneys seems to generate from accumulation of adipose tissue around the organs emphasizing the crucial function of visceral obesity in the development of renal disease.
Phytochemicals are the bioactive compounds of plants that do not deliver energy and are not yet classified as essential nutrients but possess healthful properties beyond their use as macronutrients or micronutrients. The chemopreventive effects of the majority of edible phytochemicals are often attributed to their antioxidative or anti-inflammatory activities. Flavonoids are the most common phenolic compounds that are widely distributed in fruits, seeds, and vegetables. Flavonoids possess anti-inflammatory, antiviral, antioxidant, hepatoprotective, antithrombotic, anticarcinogenic, and other biological effects. Quercetin is the most abundant of the flavonoids is found in various human foods such as red onions, grapes, citrus fruits, and tea. Quercetin has a wide range of biological effects such as lowering of blood pressure, reduction of body weight, and amelioration of hyperglycemia-related diseases. Coumaric acids are organic compounds that are hydroxy derivatives of cinnamic acid is found in a wide variety of edible plants such as peanuts, tomatoes, carrots, and garlic. p-coumaric acid has marked antioxidant, anti-adipogenic and anti-inflammatory, and anti-obesity effects. Berberine is a botanical alkaloid found in the roots and barks of several plants Berberine has various pharmacological properties, including glucose-lowering, antimicrobial properties, enhances insulin sensitivity, reduces hyperlipidemia, and relieves fatty liver.
This thesis was undertaken to study the histopathological and biochemical changes that induced by high fat-high sucrose diet in rat model. Also, the study aims to evaluate the ameliorating effects of three phytochemicals (quercetin, o- coumaric acid and berberine) on the changes that induced by diet.
Fifty male rats weight 100-120 gm were used in this study. They are divided into two groups. The first (10 rats) work as normal control feed on normal chow diet. The second (40 rats) was feed on high fat-high sucrose diet for 6 weeks, then divided into 4 subgroup (10 rats each). The first subgroup work as positive control, the second, third and fourth were orally supplemented with quercetin (50mg/kg b.w), o-coumaric acid, (75mg/ kg b.w) and berberine (50mg/kg b.w) for other 6 weeks with continuous feeding on high fat-high sucrose diet. After 12 weeks from the beginning of experiments rats were killed for collection of samples (serum, liver, adipose tissue, kidney, pancreas, aorta).
The present study proved that our laboratory animal model able to induce several metabolic disorders as evidenced by histological and biochemical changes due to feeding on HFS diet. These metabolic disorders include:
a. Increase blood glucose, insulin, TG, TCh & LDL and decreased HDL levels.
b. Alterations in the lipase, glucose -6- phosphate dehyrdogenase and glycerol -3- phosphate dehydrogenase activities in hepatic and adipose tissue.
c. Alternations of some oxidative stress markers includes lipid peroxidation, nitric oxide, glutathione, supeoxide and catalase activities in serum, kidney, liver and adipose tissue.
d. Histopathological observations by light and electron microscope revealed several changes: hepatic micro and macrovesicular steatosis, hyperplasia of pancreatic islets, tubulonephrosis and vascular changes in renal tissue, and initiation of atherosclerosis in aorta.
e. Daily oral supplementation with Q, CA and BB for 6 weeks after 6 weeks of feeding on HFS diet resulted in normoglycemic and hypolipidemic action, modulation of metabolic and oxidative stress markers. In addition to partial recovery of histopathological alterations in liver, kidney, pancreatic islets of Langergans and aorta by different levels.
The present study suggests that o-coumaric acid and berberine could be considered as promising complementary treatments against metabolic disorders associated with HFS diet while quercetin needs more investigations.