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Abstract
SUMMARY
This study was carried out to investigate the toxic effects of 2,3,7,8- tetrachlorodibenzo–p-dioxin (TCDD) on albino rats. Two hundreds male albino rats of 10-12 weeks old were divided into five groups A, B, C, D and E (40 each). Exposure to TCDD was applied orally using stomach tube in both acute and long-term toxicity.
Acute Toxicity: (First experiment)
Group A: was exposed to 1/5 of LD 50 of TCDD in a calculated dose of 4.4 g/kgb.w diluted in corn oil, given as a single dose.
Group B: Another fourty rats were used as control for the acute toxicity.
Long – term toxicity: (Second experiment)
Group C: was exposed to 1/50 of LD 50 of TCDD in a calculated dose of 0.44 g/kgb.w, diluted in corn oil given (day by day) for 12 weeks.
Group D: Rats of this group exposed to TCDD in a dose of 0.44 g/kg b.w with addition of Vit C in a dose of lg/L in drinking water simultaneously with the application of TCDD.
Group E: was kept as control administered corn oil only.
Blood, bone marrow, spleen, thymus, subscapular lymphnodes, liver and kidneys samples were collected at 12, 24, 48, 72, 96 and 144 h post-exposure in case of acute toxicity, at 4, 6, 8, 10 and 12 weeks post exposure, and after 2, 4 weeks post exposure stoppage in long –term toxicity. The body weight and feed intake were recorded weekly.
Blood samples with heparin were collected for determination of WBCs count, and differential leucocytic count ,RBCs count, Hb concentration, PCV percentage. Blood samples were collected without anticoagulant to be used for Serobiochemical investigation including determination of total protein, albumin, globulin, AST, ALT,γ-GT, alkaline phosphates, creatinine, triglycerides, cholesterol, glucose and thyroxine hormone (T4) as well as the electrophoretic pattern of serum protein. Samples of bone marrow were taken from the femur bones used to make bone barrow film. Samples for histopathological examination were taken from liver, kidneys, spleen, thymus and subscapular lymphnodes.
Hematological examination revealed variable degree of microcytic hypochromic anemia in acute group, and macrocytic hypochromic anemia in long-term toxicity. These anaemias could be attributed to apoptotic cell death in circulating erythrocytes induced by TCDD through its effect on Ahr receptor in bone marrow stromal cells which reflected with hypoplasia in the bone marrow erythrocytic series .The decrease in total WBCs count, lymphocytes, monocytes and esinophils percentage in all experimental groups, was attributed to toxicity induced by TCDD toward bone marrow, the factory of production of blood cells .The myelotoxic effect of TCDD in bone marrow, led to apoptosis of its cellularity.
Serobiochemical investigation revealed hypoproteinaemia, hypoalbuminemia, hypoglobunaemia and increased activity of some enzymes related to hepatorenal functions as AST, ALT, -Gt and alkaline phosphatase. Also increased level of serum creatinine, hyperlipaemia, hypoglycemia and decreased in the thyroxine hormone level (T4) in the serum was recorded. Hypoproteinaemia, hypoalbuminemia, and increase liver enzymes were attributed to hypofunction of the liver and kidneys due to hepatopathy and nephropathy and recorded in the organs in histopathological examination. Increase creatinine level was due to the decrease in glomerular filtration of the kidney. Hypofunction of this vital organ will be reflected on the health of the rats. Hyperlipaemia, the increase of both cholesterol and triglycerides levels concentrations in the serum was demonstrated in all groups, this increase attributed to toxic effect of TCDD on the lipid metabolism as a result to liver affection and bile duct lesions. Decreased levels of glucose concentration in the serum were due to impaired gluconegenic pathway in combination with reduced feed intake. Decreased level of thyroxine hormone was due to toxic effect of TCDD on the thyroid gland.
Electrophoretic pattern of serum proteins revealed decrease in albumin and globulin fractions , and fractions. This decrease was due to degeneration and necrosis in the lymphoid organs, which observed by histopathological examination on different lymphoid organs from all groups of the experimental groups.
Histopathological investigation of liver and kidney revealed hepatopathy and nephropathy. The severest lesions were observed in the liver followed by the kidneys. The intensity of the lesions and degree of its distribution were dose related and correlated with the time of exposure of TCDD. Primary degeneration and necrosis observed in the liver and kidneys in most groups of the experiment were apparently due to the direct action of TCDD on these organs. It also might owe its origin to the hypoxia associated with anemia observed in most experimental rats. Hypercellularity of the glomerular tuft, interstitial and fibroblastic cells reaction were chronic reaction process secondary to degeneration and necrosis observed in the parenchymal cells.
Histopathological examination of spleen, thymus and subscapular lymphnodes revealed necrosis, degeneration and lymphoid cell depletion in these organs. This exhaustion of lymphoid cell population was manifested clinically by hypoglobulinaemia. This hypoglobulinaemia was an indication of immunosuppression as it was indicated by histopathological studies that necrosis and depletion involved essentially B-lymphocytes. So the humoral immunity mechanism of the rats will be suppressed. Thymus atrophy and depletion of its population essentially T-lymphocytes indicated suppression in the cellular mediated immunity mechanism. This suppression in both arms of immune system exposes the rats to different types of infection and decreases in their resistance. On the other hand the most prominent result in this study was the restoring effect of Vit C of some parameters related directly to the immune system as differential leucocytic count, bone marrow series, total protein, albumin, alpha and beta globulins and histopathological changes in the lymphoid organs, in rats exposed to both TCDD and Vit C.