الفهرس 
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Abstract
br>Type I diabetes is an autoimmune disease in which the patient’s own immune system reacts against islet antigens and destroys the β- cell. As the hyperglycemia of diabetes becomes chronic, the glucose that normally serves as substrate, fuel, and signal takes on the darker role of toxin. Diabetes is associated with oxidative stress, low antioxidant system and high risk for vascular disease and aggressive lipid management is generally necessary. This work deals with the study of treatment of diabetes mellitus with antioxidants (taurine and selenium), immunosuppressive agent (azathioprine) or both of them as a strategy for amendment and improvement its biochemical pathways, as well as their possible role in amelioration of spleen and thymus tissues deteriorations caused by the disease has also been investigated.
Fifty adult male albino rats, Sprague Dawely strain weighing 100-150 g were used. The animals were classified into five groups as following:
Group (1): was used to study the normal control status.
Group (2): was used to study the diabetic control status.
Group (3): was used to study the effect of antioxidants in diabetes treatment.
Group (4): was used to study the effect of immunosuppressive agent in diabetes treatment.
Group (5): was used to study the effect of both antioxidants and immunosuppressive agent in diabetes treatment.
A mild diabetic state were induced to groups 2,3,4 and 5 by two consecutive intra peritoneal injection of streptozotocin (STZ), with a dose of 30 mg/kg body weight for 24 hours apart. The diabetic rats were daily received antioxidant, selenium and / or immunosuppressive agent, via oral intubations, starting 24 hours after diabetes induction for a period of three months.
Blood glutathione, plasma glucose and insulin, erythrocytic lipid peroxides and glutathione-peroxidase, serum LDH, total lipid, total cholesterol, triglycerides, HDL- cholesterol, LDL- cholesterol and glucose-6-phosphate dehydrogenase and liver glycogen were estimated. Specimens of spleen and thymus were collected for histopathological examination.
Diabetic rats exhibited an elevation in plasma glucose, serum lactate dehydrogenase, serum total lipid, total cholesterol, triglycerides, LDL-cholesterol and erythrocytic lipid peroxides content and a decrease in plasma insulin, liver glycogen, HDL-cholesterol, blood glutathione, erythrocytic glutathione peroxidase, and serum glucose-6-phosphate dehydrogenase in comparison with control rats. Treatment of diabetic rats with either taurine and selenium or azathioprine managed to induce improvements. Treatment with both of antioxidants and the immunosuppressive agent was more effective where the estimated levels tend to be as normal ones.
The spleen sections of diabetic rats showed marked signs of separation the germinal center from the red pulp. The red pulp showed impressive dilated sinuses and many pyknotic nuclei. White and red pulps areas were infiltrated with interstitial hemorrhagic alterations. Central arterioles walls in the white pulp appeared thickened.
Thymus from diabetic rats presented a very advanced atrophy, characterized by lobules with disappearance of cortical-medullary distinction, disarrangement and aggregation of lymphocytes as compared to control animals. There were wide spaces in the medulla could be observed easily.
Treatment with antioxidants or immunosuppressive agent managed to induce ameliorative patterns in spleen and thymus. Treatment with both of antioxidants and immunosuppressive agent stimulated more effective amended profiles in both spleen and thymus than the antioxidants or the immunosuppressive agent separately.
The present results indicated that treatment with both antioxidants and the immunosuppressive agent daily is impressive in control of hyperglycemia and lipid management in order to lower the oxidative stress. This is through the efficacious antioxidant defense effect of taurine and selenium as free radical scavengers which protects type I diabetics from lipid peroxides formation in addition to a similar efficacious immunosuppressive agent effect of azathioprine as immunosuppressive agent against diabetic complications. This treatment suppresses the diabetic autoimmunity came from cytokineses (IL-1β, TNF-α and IFN- γ) which release free radicals that cause β-cell destruction that is followed by hyperglycemia. The endogenous antioxidants as glutathione and antioxidant enzymes as glutathione peroxidase and glucose-6-phosphate dehydrogenase were intiated to play their roles against free radical formation, an action which pervents cell injury in spleen and thymus.
Conclusion:
Treatment with both of antioxidants and the immunosuppressive agent at time of onset or soon after its diagnosis can be effective in diabetes disease which prevents progressing of diabetes which attenuates its autoimmunity, lipid peroxides and complications as well as ameliorates the spleen and thymus tissues deteriorations induced by diabetes.