الفهرس 
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Abstract
Diabetes mellitus (DM) is a metabolic disorder of multiple etiologies characterized by chronic hyperglycemia with disturbances of carbohydrates, fat and protein metabolism resulting from defects in insulin secretion, insulin action, or both. The effects of DM include long term damage, dysfunction and failure of various organs. In its most sever forms, ketoacidosis or a non- ketotic hyperosmolar state may develop and lead to coma and in absence of effective treatment, death. The long term effect of DM include progressive development of the specific complication of retinopathy with potential blindness, nephropathy that may lead to renal failure, and /or neuropathy with risk of foot ulcers ,amputation, and features of autonomic dysfunction, including sexual dysfunction .People with diabetes are at increased risk of cardiovascular, peripheral vascular and cerebrovascular disease.
Hyperlipidemia is a medical condition characterized by an elevation of any or all lipid profile and/or lipoproteins in the blood. One of the most common diabetic complications is hyperlipidemia. It is also called hypercholesterolemia/hyperlipoproteinemia. Although elevated LDL-C is thought to be the best indicator of atherosclerosis risk, dyslipidemia (abnormal amount of lipids in the blood) can also describe elevated total cholesterol (TC) or triacylglycerols (TAGs), or low levels of high density lipoprotein cholesterol (HDL-C).
Psyllium has a long history of use as a dietary fiber supplement, primarily as a gentle bulk-forming laxative to promote the regulation of large bowel function, but it has also, a potential role in the treatment and prevention of bowel diseases such as diverticulosis, irritable bowel syndrome and inflammatory bowel disease, and could even play a protective role in the prevention of colon cancer. During the last decade, dietary supplementation with Psyllium has been shown to lower blood cholesterol level (especially LDL cholesterol) and to maintain blood glucose homeostasis, which together are the most effective preventive measures against diabetes and cardiovascular diseases. The intent of this study is to summarize the functional benefits of psyllium fiber consumption and to explore the potential application this fiber has for first-line dietary prevention of these diseases and disorders. Psyllium bioactive components may have hypoglycemic and hypolipidemic activities.
The present study was designed to investigate the hypoglycemic and hypolipidemic effects of diatery psyllium seeds supplementation in two different doses (0.5 % and 1 %) in diabetic, hyperlipidemic and diabetic hyperlipidemic rats.
Eighty adult male albino rats Sprague Dawley strain weighing 150±5 g were divided into ten groups (8 rats/each), and hyperlipidemia was induced in six groups (G3,4,7,8,9 and 10) by feeding them the high fat high cholesterol diet (HFHC) for 10 days, while the remaining four groups (G1,2,5 and 6) continued feeding on standard balanced diet. Then , six groups (G2,4,5,6,9and 10) were rendered diabetic by means of a single intraperitoneal (i.p.) injection of a freshly prepared STZ 50 mg/Kg b.w. dissolved in 0.1 M sodium citrate buffer pH4.5 and injected within 15 min of preparation to rats. As STZ is capable of inducing fatal hypoglycemia as a result of massive pancreatic insulin release, STZ-treated rats were allowed to drink 5% glucose solution to overcome hypoglycemia after STZ injection. And the remaining four groups (G1, 3, 7 and 8) were injected interaperitoneally (i.p.) by saline solution.
The experimental groups were divided as follow:
group 1: Normal rats fed on standard balanced diet (-ve Control) [NC].
group 2: Diabetic rats fed on standard balanced diet (Diabetic Control) [DC].
group 3: Hyperlipidemic rats fed on HFHC diet (Hyperlipidemic Control [HC].
group 4: Diabetic Hyperlipidemic rats fed on HFHC (Diabetic Hyperlipidemic Control) [DHC].
group 5: Diabetic rats fed on diet supplemented with 0.5%Psyllium [D+0.5%Psy].
group 6: Diabetic rats fed on diet supplemented with 1% Psyllium seeds [D+1% Psy].
group 7: Hyperlipidemic rats fed on HFHC diet supplemented with 0.5% Psyllium seeds [H+0.5%Psy].
group 8: Hyperlipidemic rats fed on HFHC diet supplemented with 1% Psyllium seeds [H+1%Psy].
group 9: Diabetic hyperlipidemic rats fed on HFHC diet supplemented with 0.5 % Psyllium seeds [DH+0.5% Psy].
group 10: Diabetic hyperlipidemic rats fed on HFHC diet supplemented with 1.0% Psyllium seeds [DH+1% Psy].
Food intake was recorded daily and rats were weighed weekly to monitor the body weight changes and to calculate feed efficiency ratio (FER).
At the end of the experiments (6 weeks) the animals were scarified under ether anesthesia and blood samples were collected from portal vein. Also, Organs (liver and pancreas) were immediately removed, washed and weighed to calculate the relative organs weight , then pancreas were preserved in 10 % formalin solution for microscopic examination. The following biochemical parameters were measured:
• Glucose and insulin levels
• Homeostasis model of insulin resistance (HOMA-IR)
• Pancreatic β cell function (HOMA-β–Score)
• Serum lipid profile (TL,Pl,TAGs,HDL-C,LDL-C and VLDL-C) levels.
• Heart disease risk ratios AI, LDL-C/HDL-C , TC/HDL-C and TAGs/HDL-C levels.
• Serum TAC, MDA, and OSI levels.
• Blood Gpx and G6PD activities
• Liver cholesterol and triacylglycerols levels.
• Also, microscopic examination of pancreas was performed.
The result of our study can be summarized as follows:
(1) Food intake,body weight change, feed efficiency ratio and relative organs weight in experimental groups:
Diabetes mellitus caused a marked increase in food intake and a marked decrease in body weight and FER. While, there was marked increase in food intake accompanied by marked increase in body weight in hyperlipidemic group. Administration of psyllium seeds tends to restore body weight gain near normal in all treated groups. Also, there were marked increase in relative liver weight in all +ve control groups. while, after psyllium supplementation relative liver weight neared to normal weight. Moreover, there was marked decrease in relative pancreatic weight in STZ-induced diabetic rats. While, there were a significant increase in relative pancreatic weight in hyperlipidemic group. Treatment with psyllium seeds restored relative pancreatic weight near normal. The effectiveness of psyllium supplementation was dose dependent.
(2)Serum (glucose and insulin level), insulin resistance (HOMA-IR) and beta function index (HOMA-β) levels in experimental groups :
Diabetes mellitus causes chronic hyperglycemia and hypoinsulinemia in STZ-induced diabetic and diabetic hyperlipidemic rats that reflect the destruction of β-cells of pancreas. Psyllium seeds improve glucose hemostasis by decreasing blood glucose, increasing β-cell function and increasing serum insulin levels. While, there were marked hyperinsulinemia with normal serum glucose in hyperlipidemic group accompanied by marked increase in insulin resistance. Psyllium seeds supplementation improve glucose hemostasis by decreasing blood glucose and increasing serum insulin level in diabetic group. However, psyllium supplementation for hyperlipidemic groups decrease insulin resistance and improve hyperinsulinaemia. Generally, the improvement was dose dependent.
The glucose-reducing action of psyllium is proposed to the formation of a viscous gel in aqueous solution. This gel may hinder the access of glucose to the absorptive epithelium of the small intestine, thereby blunting postprandial glucose peaks. In addition, soluble fiber may delay gastric emptying, thus slowing carbohydrate uptake.
(3) Lipid profile levels :
Diabetic, hyperlipidemic and diabetic hyperlipidemic rats showed disturbance in serum lipid profile which detected by the elevation of serum TL, PL, TC, TAGs, LDL-C,VLDL-C and marked decrease in HDL-C level. Our present study proved the hypolipidemic effect of psyllium seeds as its administration caused a marked dose dependent decrease in serum TL, PL, TC, TAGs, LDL-C,VLDL-C and noticeable elevation in HDL-C level compared to normal group. As well as, the present study illustrated that psyllium seeds possess protective effect against cardiac diseases which approved by marked decrease of AI, LDL-C/HDL-C, TC/HDL-C and TAGs/ HDL-C ratios. These parameters were elevated in all +ve control groups.
One of the cholesterol reduction mechanisms is that psyllium stimulates bile acid synthesis through 7-hydroxylase activity. Another mode of action of psyllium fibers in reducing cholesterol is diversion of hepatic cholesterol synthesis to bile acid production. Psyllium causes inhibition of hepatic cholesterol synthesis by propionate and secondary effects of slowing glucose absorption from gut.
(4) Lipids peroxidation and antioxidants status:
The present study illustrated disturbance in total antioxidant status which indicated by a marked increase in lipid peroxidation that can be reflected by increasing serum MDA level and OSI index and marked decrease in TAC level and antioxidant enzymes including GPx and G6PD activities which inferred by the reduction in their activities in diabetic, hyperlipidemic and diabetic hyperlipidemic groups.
Administration of psyllium seeds to diabetic, hyperlipidemic ,diabetic hyperlipidemic rats improve the antioxidants status and lipid peroxidation there were manifested by the marked increase in TAC level, GPx and G6PD activities and marked decrease in MDA level and OSI index. Generally, the antioxidants effect of psyllium seeds was dose – dependent. Psyllium seeds have antioxidant capacity to scavenge ROS, prevent glycation of protein and restore the antioxidants enzymes near normal.
In the present study decreasing lipid peroxidation by administration of psyllium seeds may be attributed to psyllium ability to modulate lipid parameters, protein glycation , glucose-autooxidation, thus leading to decrease production of lipid peroxidation products and may be attributed to its antioxidant activity, because psyllium have many phenolic compounds, which have inhibitory effects on lipid peroxidation and preserve the antioxidant compounds.
(5) Hepatic lipid profile:
Results also, indicated marked elevation in liver cholesterol and triacylglycerols levels in diabetic, hyperlipidemic, and diabetic hyperlipidemic groups. Supplementation of psyllium seeds amelioratethe lipid levels to normal range.
(6) Microscopic examination of pancreas:
Pancreatic tissue from diabetic rats showed that STZ reduced cellularity of pancreatic island which replaced by hyaline deposition. The blood vessels wall thickened due to the hyaline deposition. Although, on hyperlipidemic rats there were fatty acid depositions in the exocrine pancreatic tissue, there was no change in pancreatic island. Results showed that supplementation with the tested doses of psyllium seeds caused a significant amelioration of the pancreatic tissue. The best effect was noticed in 1% psyllium which improves pancreas morphology. Psyllium seeds provided definite protection against the effect of long term diabetes on the islet cells; they reduce cell lose and rate of apaptosis. Reactive oxygen species play a vital role in apoptosis and antioxidants from psyllium seeds can block or delay this process. Results indicated the role of psyllium seeds in mediating mechanisms in protecting the islet cells from diabetes induced disorders. The reduction of hyperglycemia may be a cause of such protection.