الفهرس 
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Abstract
The present study evaluated the hypoglycemic effect of the manufactured organosulpher compounds; taurine, diallyl disulphide, dimethyl disulphide and dipropyl disulphide and compared this effect with the therapeutic hypoglycemic drug, gliclazide (diabyl) in vivo, in vitro and in situ.
In the present study, intera peritoneal injection of a single dose of 45 mg/kg b. wt. streptozotocin to adult male albino rats induced mild hyperglycemia and hypoinsulinemia with a decrease in liver glycogen and an increase in gluconeogenic enzymes activities. It also induced a general increase in total lipids, triglycerides, total cholesterol and LDL-cholesterol and a decrease in HDL-cholesterol. However, the results showed a decrease in total protein concentration, protein fractions, albumin : globulin ratio and globulin fractions and induced a disturbance in individual amino acids concentration. Regarding the immunological study, streptozotocin injection induced immunodeficiency explained by a decrease in total immunoglobulins and a decrease in Ig M, Ig G and Ig A. At the same time, this dose showed vacuolations in the cytoplasm and hydropic degenerations of many {3-cells in the islet of Langerhans which resulted in a decrease in serum insulin concentration.
After being diabetic the mild rats were subdivided into six groups one settled diabetic and subdivided into two subgroups, one was administered distilled water along the time of the experiment and considered as a control for the water-soluble treatment groups and the other diabetic subgroup was administered corn oil along the experimental time and regarded as a control for the oil-soluble treatment groups.
The other five groups were treated with 12.8 mg/kg b. wt. gliclazide, 30 mg/kg b. wt. taurine and 100 mg/kg b. wt. of the three disulphide groups (diallyl disulphide, dimethyl disulphide and dipropyl disulphide). The doses selected for the organosulpher compounds depend on the preliminary study of the potency of the three different doses for each agent. As the diabetic group (with its two subdivisions) being control for the treated groups, there was another 7 TH normal group kept under the same laboratory conditions to be a control for the diabetic-untreated groups.
At the end of the experiment, in comparison with the diabetic group, the treatment either with gliclazide or the organosulpher compounds significantly ameliorate the oral glucose tolerance test (OGTT), significantly increased liver glycogen and significantly decreased the serum gluconeogenic enzymes, glucose-6-phosphate dehydrogenase (G-6-PDH) and lactate dehydrogenase (LDH), while glucose-6-phosphatase (G-6-Pase) was significantly decreased with the three tested disulphide compounds and non-significantly decreased with gliclazide and taurine. Also, the serum insulin was significantly increased after the treatment with the tested agents.
An important trial of the present study is to confirm the in vivo studies by carrying out the in vitro experiments. The addition of gliclazide and the organosulpher compounds on the isolated islets of the rats increased the insulin release. The insulin released in the presence of 2 mM or 10 mM glucose was significantly increased by the addition of the two tested doses of taurine, while it was increased significantly by the doses of gliclazide and the disulphide compounds and also, increased non-significantly with the low doses of these agents. These results indicated that taurine is initiator and potentiator for insulin release with the low and the high doses, while the other agents are initiators and potentiators in a dose-dependent manner .
Regarding the intestinal glucose absorption and the peripheral glucose uptake, there was a significant decrease in the intestinal absorption by increasing the doses of the tested agents and the peripheral glucose uptake increased parallel with the increase in doses of the tested agents.
This study proved that, organosulpher compounds have good effects on carbohydrate metabolism, by improving glucose tolerance, increasing liver glycogen storage, increasing the effect of gluconeogenic enzymes, increasing insulin effects or increasing insulin secretion as the (3-cell number increased, decreasing the intestinal glucose absorption and increasing peripheral glucose uptake.
Furthermore, serum lipidogram were also ameliorated in all treated groups with a significant decrease in serum total lipids, triglycerides, total cholesterol and LDL-cholesterol while, HDL-cholesterol was significantly increased with gliclazide only. Moreover, the cardio-vascular risk factor (CVR) was also decreased significantly after all treatments. The present data revealed that gliclazide and the tested organosulpher compounds have good hypolipidemic and cardioprotective effects on the diabetic rats by getting rid of the excess lipids or by decreasing their synthesis.
Regarding the protein profile, all the treatments showed a significant increase in serum total protein, except for diallyl disulphide where the increase was non-significant. The treatments either with gliclazide or the organosulpher compounds resulted in a significant increase in protein fractions, albumin and globulin while, the albumin : globulin ratio was significantly increased with diallyl disulphide and dimethyl disulphide and non-significantly increased with gliclazide, taurine and dipropyl disulphide. For the globulin fractions; a-globulin showed a significant increase with taurine, diallyl disulphide and dipropyl disulphide while the increase was non-significant with gliclazide and dimethyl disulphide. (3-globulin showed a significant increase with all the treatments except with diallyl disulphide while y-globulin showed a significant increase with all the treatments except for taurine. For serum amino acids concentration, there was a general increase with all treatments for aspartic acid and alanine and a general decrease with all treatments for arginine while for the other amino acids each treatment affects each amino acid concentration individually as insulin plays an important role in the alterations of some amino acids. Therefore, the effect of the tested materials on protein metabolism in diabetic rats can be suggested to be mainly due to their effect on decreasing gluconeogenesis or increasing proteogenesis by increasing insulin level.
The immunological study showed a significant increase in total immunoglobulins with all the treatments except with diallyl disulphide, where the increase was non-significant. The immunoglobulin M showed a significant decrease with diallyl disulphide and dimethyl disulphide, a non-significant decrease with dipropyl disulphide and a non-significant increase with gliclazide and taurine. The immunoglobulin G showed a
significant increase with dipropyl disulphide only while the increase was non-significant with the other treatments. On the other hand, the immunoglobulin A showed a significant increase with all the treatments except with gliclazide where the increase was non-significant.
In the histopathological study, the treatment with gliclazide and the organosulpher compounds stimulated the recovery of some of the islets cells as it became more organized with less vacuolations and less necrotic cells.
In conclusion, our study revealed that gliclazide as well as the organosulpher compounds have both pancreatic (secretogogue or insulinotropic) and extrapancreatic (insulin mimetic) effects, as they have hypoglycemic, hypolipedemic, proteogenic and immunogenic effects. The study, also, proved that the tested agents have a beneficial effect on all aspects of disturbed metabolism of streptozotocin-diabetic rats, so they may act as good hypoglycemic agents in diabetes apart from using chemical drugs with possible side effects or using the whole extracts of medicinal plants with their unuseful or unsafe components.