الفهرس 
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Abstract
Atherosclerosis is a progressive vascular disease characterized by endothelial dysfunction, upregulation of cell adhesion molecules, accumulation of lipids, macrophages, smooth muscle cells (SMCs) and fibrous tissue in the arterial intima and represents one of the leading causes of cardiovascular morbidity and mortality.
Atherosclerosis commences with the deposition of lipids in the artery wall. Hyperlipidemia, including hypercholesterolemia and hypertriglyceridemia, is a major risk factor for the development of cardiovascular diseases (CVD). Trapped lipoproteins are chemically and enzymatically modified to yield pro-inflammatory species that induce adhesion molecule expression on endothelial cells leading to the recruitment of multiple species of immune cells and a chronic inflammatory response. Ongoing remodeling of the vessel and later morphological changes generate “vulnerable” plaques, the acute rupture of which generates the clinical event.
The major medical therapies are lipid lowering agents. Although these drugs are amongst the most efficacious in cardiovascular medicine, the maximum effect is limited to an approximately 30% reduction in cardiovascular events.
Aim: The purpose of this study was to examine the efficiency of using either cold or hot UFP algal extracts on the prevention of hyperlipidemia, hypercholesterolemia- induced in rats fed high fat, high cholesterol diets.
Materials and Methods:
Sulfated polysaccharides (SPs) from Ulva fasciata were extracted in both cold and hot water and precipitated by ethanol, then orally administrated to hypercholesterolemic (HC) rats, for four weeks to evaluate the antihypercholesterolemic and antioxidant actions. Fluvastatin Lescol) was used as a reference drug.
A total of 105 rats were used in this study and were randomly divided into 7 groups, among them 3 normal diet groups fed on rat chow without any additives (given normal diet and distilled water), the first normal group (n=15) used as negative controls, and the other 2 normal groups,
each (n=15), received both cold and hot UFP algal extracts. The other 4 groups kept on HC-diet for twelve weeks. Hypercholesterolemia was experimentally induced by administration of cholesterol at a dose of (30mg/0.3ml olive oil as a vehicle for cholesterol /1 kg animal), lard fat was mixed with normal diet (One kilogram of animal lard was added to 5Kgs of normal diet). The occurrence of hyperlipidemia was determined by measuring lipid profile (Duration of treatment: 4 weeks).
The HC-rats were subdivided into four groups:
Group 1: is served as positive control rats.
Group 2: HC-rats received an oral dose of cold extract.
Group 3: HC-rats received an oral dose of hot extract.
Group4: HC-rats received an oral dose of fluvastatin.
Results: The present study showed that cholesterol-enriched diet caused a significant surge in total cholesterol, total lipids, and triacylglycerols, serum LDL-C, VLDL-C and atherogenic index (AI), whereas high density lipoprotein cholesterol (HDL-C) was significantly decreased as compared to normal control group. Furthermore, AST, ALT, ALP, TB were significantly elevated, whereas TPand albumin were significantly reduced. Moreover, hyperlipidemia induced mild oxidative stress in terms of elevated hepatic levels of malondialdehyde (MDA) and nitric oxide (NO) and decreased level of reduced glutathione (GSH). In addition, adhesion molecules (VCAM-1) and (ICAM-1) increased, as well as, inflammatory markers (TNF-α, MPO and CRP), in contrast; antiatherogenic IL-10 was significantly reduced. High fat diet intake caused a highly significant elevation in serum urea, creatinine concentration.
Aorta histopathology: In addition, hyperlipidemic rats exhibited histological abnormalities manifested as perivascular hemorrhage, scattered foam cells in intima and subintima region, vacuolation of the tunica media and minor thickening in aorta wall, suggesting the commencement of atherosclerosis.
Liver histopathology: Hepatocytes of HC-rats showed severe degeneration with diffuse vacuolar degeneration and necrosis. The endothelial lining of the central vein exhibited more cell injury with increased accumulation of fat vacuoles in the hepatocytes.
Kidney histopathology: Light microscopy observations of HC-rats revealed, mild glomerular injury with mild vascular and inflammatory changes, signs of moderate vascular congestion, mesangial hyperplasia and dilatation of vascular lumen with no evidence of fat deposits.
These effects were reversed by oral administration of cold and hot UFP extracts to HC-rats, as it showed a significant ameliorative action on lipid profile, represented by significant decrease in plasma total
cholesterol, non-HDL cholesterol, total lipids, triacylglycerols and LDL-C, and the hepatic non-enzymatic antioxidant defenses were ameliorated by promoting the production of GSH and reducing MDA and NO, as well as, suppressing the expression of VCAM-1 and ICAM-1,
with increased anti-inflammatory IL-10 and decreased inflammatory cytokines (TNF-α, MPO and CRP), thereby suppressing lipid accumulation and inflammatory cell infiltration. Furthermore, serum activities of AST, ALT, alkaline phosphatase (ALP), TB, TP and albumin were also improved, as well as, glucose that restored to its normal level.
Histopathology: Normal histological structure was observed in aorta of treated rats with cold and hot UFP extracts, and associated with a significant decrease in atherosclerotic plaque progression and endothelial function improvement, as well as, improvement of liver and kidney histology.