الفهرس | Only 14 pages are availabe for public view |
Abstract Diabetes is the most prevalent diseases in the world where the impact on mortality and national income of individuals and communities rate. Diabetes, hyperglycemia, occurs due to lack of insulin secretion from the β cells in the pancreas (type 1) or the insulin does not work as a result of imbalance in the ability of insulin receptors on the cells (type 2) or both reasons. Diabetes causes dysfunction in the immune system and the rate of secretion of cytokines which increases the rate of apoptosis and fibrosis. Experimentally type 1 diabetes can be induced by injecting animals with STZ that destroy β cells, leading to hperglycemia and hpoinsulinemia. The present study, experimental model of diabetes, was done to find out the effects of disease on the immune organs, in addition to find out treatment can reduces these effects. Therefore, this study was conducted in order to evaluate the effect of diabetes induced by STZ on the immune and others organs and the role of camel milk WP in the treatment of these negative influences. In this study, 45 male albino mice were purchased from Theodore Bilharz Institute in Cairo were divided into three groups, 15 mice each. The first was used as control and the other two groups were injected interperitoneally with STZ (60 mg/kg) once a week for three weeks. During the dosing blood samples were taken to assess the level of glucose, mice which had blood glucose 220 mg/dl or more was considered diabetic. After making sure the mice becomes diabetic, one group left as diabetic control, and the other was treated with CWP (100 mg/kg) for four consecutive weeks. CWP was extracted in the Dairy Department, Faculty of Agriculture, Assiut University from camel milk were purchased from Marsa Matrouh Governorate. After the expiration of the treatment, all mice were anesthetized with ether and killed for collection of blood samples and organs (liver, kidney, spleen, testis, thymus, BM) for biochemical analysis and histological observation. The study concluded the following results: 1. Injected mice with STZ showed hyperglycemia, hpo-insulinemia and increase in the levels of pro-inflammatory cytokines (IL-6, IL1β and TNF-α), while post-inflammatory cytokines (IL-2, and IL-4) showed decrease in comparison with the control group. 2. Diabetic mice showed an increase in the leukocytes and differential leukocytes count, and a decrease in the erythrocytes count and MCH, MCHC MCV, and MPV parameters. 3. Also, diabetic mice showed alterations in oxidative stress makers in different or organs as follows: Increase in the LPO in the blood and tissues of the liver, kidney and testes. Decrease in NO in the blood and liver tissue only. Increase in carbonyl protein in liver, kidney and testes. Non-significant change in the GSH level of in the liver, kidney and testes. Non-significant change in the activity of SOD in the tissues of the liver, kidney and testes. 4. Western blot analysis significant increase in the expression of ATF-3, a decrease in phosphorylation of AKT and IκB-α with an increase in apoptosis of lymphocytes and increased in the expression of Bax in BM, thymus and spleen and decreased in Bcl-XL in BM, thymus and spleen. 5. Microscopic examination by light microscope revealed pathological changes as follows: Shortage in the constituent cells of the blood cells in the BM. Increase collagen fibers in capsule of thymus, necrosis of the cells, and the decomposition of vascular tissue in the epithelial lining of the gland. Immunohistochemical analysis also showed an increase in T cells in the marrow and cortex of gland. Thickening in the capsule of the spleen due to the increase of collagen fibers and increase in the number of phagocytic cells to macrophages with a shortage of lymphocytes. Immunohistochemical analysis also showed an increase in T cells and a decrease in B cells. Presence of congestion, hemorrhage, vacuoles, necrosis and Pyknotic nuclei, and cellular infiltration in the liver The presence of necrosis of beta cells Islands of Langerhans with increased collagen fiber around the blood vessels in the pancreas. The presence of congestion, hemorrhage and focal cell morphology and Pyknotic nuclei, with a widening of Malpighian corpuscles in the kidney. Appearance of incomplete spermatogenesis with giant cells in the testis. 6. Treatment of diabetic mice with CWP results in improvement in all the biochemical changes in the blood and tissues of the liver, kidney, testes, leading to an improvement in histological tissue to the liver, kidney, testes, pancreas, spleen installation and bone marrow. In addition, restored the expression of ATF-3 and phosphorylation of AKT, IκB-α, and the expression of Bax and Bcl-XL in BM, thymus and spleen. Resulting in a lack of programmed cell death in lymphocytes with improved oxidative stress and inflammatory cytokines. 7- In conclusion our obtained results find the ability of CWP to reduce the inflammation, oxidative stress, and immune dysfunction due to metabolism of STZ and hyperglycemia as diabetic complications. |