الفهرس 
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Abstract
Copper and cobalt are essential elements in humans and animals and have both beneficial and harmful effect on human health, they are necessary for life at very low concentrations, but when their concentrations increase, they become toxic and interfere with cell metabolism
The present study aimed to investigate the chronic toxicity of copper sulphate and cobalt chloride on male white albino rats .
This study was conducted on 100 mature male albino rats divided into five groups, group (I) served as control group, group (II) and group (III) given copper sulphate 1/10 LD50 and 1/5 LD50 respectively, group (IV), group (V) given cobalt chloride 1/10 LD50 and 1/5 LD50 respectively. All groups treated orally three doses every week for six months.
Whole blood was collected for hematological investigation (RBCs, WBCs, Hb concentrations, PCV%) and blood glucose level. Serum was collected for biochemical analysis. Testis and tail of epididymes collected for spermogram. Samples of liver and kidney were collected for residues analysis, and tissue samples of liver, spleen, kidney, brain, testis, heart, thymus gland and lung were collected for histopathological examination.
The results revealed a significant decrease in mean body weight of rats . These reduction was clear in groups treated by high doses. The relative organs weight of liver, kidney, heart, lung and spleen of treated groups showed a significant increase, while relative testis weight showed a significant decrease (p< 0.05).
RBCs, WBCs, Hb concentrations and PCV% of treated rats with copper sulphate showed a highly significant decrease (p< 0.05). while RBCs in treated groups with cobalt chloride induced a highly significant increase (p< 0.05).
There was a significant increase in total leucocytes, lymphocytes and ; band cell (immature neutrophile) counts of all treated rats at the 2nd, 4th and 6th month of experiment compared to the control group (p< 0.05).
Total serum protein and albumin levels of treated rats significantly decreased. The significances were prominent after the 6th month of treatment specially in groups received the high dose of copper sulphate or cobalt chloride (p< 0.05) .
The study recorded a highly significant elevation of AST, ALT, AP , GGT, urea , uric acid and creatinine in the sera of all treated rats specially after the 6th month of treatment specially in groups received high dose of copper sulphate and cobalt chloride (p< 0.05).
There was a significant increase in calcium levels at the 4th and 6th months in rats treated by copper sulphate and cobalt chloride. While a significant decrease in potassium levels in serum treated rats at the 2nd, 4th and 6th month. Regarding manganese levels, there was a non significant decrease at the 2nd month, while at the 4th and 6th month there was a significant decrease in serum treated-rats compared to the control group (p< 0.05) .
There was a significant decrease in T3 and T4 levels in the treated groups. While there was a significant increase in TSH levels in the treated groups compared to the control group (p< 0.05) .
There was a significant increase in blood glucose level in treated groups compared to the control group (p< 0.05) .
Regarding the effect of copper sulphate and cobalt chloride on sperm cell count and morphological abnormalities there were a significant decrease of sperm cell count and elevation of sperm abnormalities specially in groups received the high dose of copper sulphate and cobalt chloride after 6 months of treatment (p< 0.05).
The antioxidant status including GSH and GST showed a significant decrease in the treated groups, while MDA showed a significant increase in these groups compared to the control group (p< 0.05) .
The tumor markers revealed that alfa feto- protein was not detected in the treated groups except at the 6th month of the experiment in groups received the high dose of copper sulphate (p< 0.05).
Copper and cobalt concentrations levels were detected in liver and kidney of rats in the treated groups at the 4th and 6th month of the treatment in comparison to the permissible limit (p< 0.05).
The histopathological examination of the liver of rats in all treated groups revealed diffuse hepatic degenerative changes in the form of vascular, hydropic and fatty degeneration at the early stage of examination. These changes were more severe in rats given the high dose 1/5 LD50. At end of experiment inflammatory cellular infiltration, diffuse fatty degeneration, hepatic cell disarrangement with bile duct hyperplasia and small neoplastic foci characterized by a collection of dysplastic hepatocytes with a decreased cell volume, hyperchromatic or vesicular nuclei, nuclear pleomorphism, increased nucleocytoplasmic ratio and pale cytoplasmic eosinophilia were seen. The examined spleen of rats showed lymphoid depletion which increased in its severity with time. Renal tubular necrosis was the predominant microscopic changes in the examined kidneys of rats in all groups. These changes were severe at the end of experiment particularly in rats given the high dose. The recorded brain histopathological changes were represented by congestion, cerebral edema, with neural degeneration and neurophagia. Testicular degeneration was found in the testes of examined rats mostly at the late stages of experiment and in rats given the high dose. The examined lungs showed multiple lymphocytic cellular infiltration with desquamation of the bronchial lining epithelium. Moreover, cardiac hyalinosis and congestion were observed in the examined heart mainly at the end of experimental period. The examined thymus of rats showed hyperplasia and stratification of the follicular cells (goiter in rats).