الفهرس 
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Abstract
Hyperlipidemia is clinically a common disease with the rapid improvement of economy and quick changes in nutritional stage. The incidence of hyperlipidemia is threatening people’s health. A number of studies indicate that hyperlipidemia is an independent risk factor for stroke, coronary heart disease, cardiovascular disease (CVD), sudden cardiac death, and is closely related to the occurrence of non-alcoholic fatty liver disease (NAFLD).
Diabetes mellitus is a metabolic disease resulting from defects in insulin secretion or insulin action or both. This disease is often associated with high blood glucose (hyperglycemia), increase levels of TC, TG, LDL-C (hyperlipidemia), but decrease levels of HDL-C. The hyperglycemia can increase the incidence of many complications in diabetic patients, while hyperlipidemia contributes to the development of coronary heart diseases and atherosclerosis, which are the most common cause of mortality and morbidity
The main target of this study was to examine the efficiency of using either aqueous polysaccharides extracts of Enteromorpha intestinalis or Dictyopteris membranacea on the prevention of some metabolic disorders.
A total of 105 rats were used in this study and were randomly divided into 7 groups (n=15) for each group, among them 3 normal diet groups fed on rat chow without any additives (given normal diet and water). First of them used as negative controls, and the other groups, each received aqueous Enteromorpha intestinalis or aqueous Dictyopteris membranacea extracts. Type 2 diabetes was simulated by induction of two simultaneous steps which are induction of systemic insulin resistance that was achieved by introduction of high fat diet (20 % w/w animal lard added to chow) in addition to daily oral injections of cholesterol (30 mg/kg) for twelve consecutive weeks. Then induction of insulin insufficiency achieved by injection of low dose of STZ (40 mg/kg)
(Duration of treatment :4 weeks)
The hypercholesterolemic - hyperglycemic (HC-HG) were subdivided into four groups:
group 1: served as positive control rats.
group 2: HC-HG rats received an oral dose of aqueous extract of Enteromorpha intestinalis.
group 3: HC-HG rats received an oral dose of aqueous extract of Dictyopteris membranacea.
group 4: HC-HG rats received an oral dose of reference drugs (glibenclamide along with fenofibrate).
The present study showed that cholesterol-enriched diet caused a significant surge in total cholesterol, total lipids, TGs, serum LDL-C, VLDL-C and AI, whereas HDL-C was significantly decreased as compared to control group. Furthermore, ALT, AST, GGT, ALP and TB were significantly elevated, whereas TP and albumin were significantly reduced. Moreover, hyperlipidemia and hyperglycemia induced oxidative stress in terms of GPx, SOD, NO and Cat. In addition, hyperglycemic state was observed by elevated levels of FBG while decreased in serum insulin. HC-HG caused a highly significant elevation in serum urea, creatinine concentration, as well as, inflammatory markers IL-6 and CRP. Furthermore, increased in cardiovascular biomarker CK-MB and LDH in addition to variations in LDH-isoenzymes.
Liver histopathology: HC-HG rats showed inflammation in the cells with fat vacuoles in the thick capsule with underlying vacuolar and fatty changed hepatocytes in the parenchyma accompanied with congestion in the portal vein associated with inflammatory cells infiltration surrounding the bile ducts and in the central vein and sinusoids.
Kidney histopathology: light microscopy observed congestion in the glomerlui of HC-HG rats associated with degeneration and coagulative necrosis in the lining epithelium of the tubules, in addition to sever congestion was noticed in the intertubular blood vessels at the cortex. While the corticomedullary portion showed focal hemorrhage in between the degenerated tubules.
Pancreas histopathology: HFD induced diabetic by STZ rats showed degeneration and atrophy in the islets of langerhans cells.
Heart histopathology: HC-HG rats exhibited histological alteration manifested as sever congestion in the myocardial blood vessels. The subendocardium showed oedema with inflammatory cells infiltration and focal hemorrhage in between the myocardial bundles.
Spleen histopathology: HC-HG rats showed lymphoid depletion in white pulps while the red one had hemosiderosis. In addition, a thickening in the capsule was observed by few inflammatory cell’s infiltration and oedema as well as the central portion of the white pulps showed lymphoid depletion.
These effects were reversed or improved by oral administration of polysaccharides of either aqueous Enteromorpha intestinalis or aqueous Dictyopteris membranacea extracts to HC-HG rats, as it showed a significant ameliorative action on lipid profile, represented by significant decrease in plasma total cholesterol, TGs, TLs, VLDL-C and LDL-C while, increase in HDL-C. The hepatic antioxidant activity was ameliorated by promoting decreasing in GPx, SOD, NO and Cat as well as suppression of the inflammatory cytokine IL-6 and CRP by suppression of the lipid accumulation and inflammatory cell infiltration. Furthermore, serum activities of transaminases (ALT, AST), GGT, ALP, TB, TP and ALB were also improved, as well as glucose and insulin levels restored to their normal levels.
Normal histological structure was observed in myocardium of treated rats with aqueous Enteromorpha intestinalis or aqueous Dictyopteris membranacea while administration of aqueous Enteromorpha intestinalis extract to HC-HG rats showed normal histological structure in liver, kidney, pancreas and spleen and were more effective than oral administration of aqueous Dictyopteris membranacea which still exhibited some histological abnormalities in these tissues.
In conclusion, the results of this study demonstrated that both algal extract especially, Enteromorpha intestinalis can be considered as a potential natural alga-derived drug and functional food for prevention and treatment of hyperlipidemia and hyperglycemia. As well as it is effective in decreasing the oxidative stress and atherosclerosis development.
Finally, these results suggest that both extracts possess anti-atherogenic, hypolipidemic, hepatoprotective, renal protection, hypoglycemic and reduced oxidative stress via inhibition of reactive oxygen species.