Toxicopathological study due to effect of different doses of Copper Sulfate ingested in rat

The object of this study were to evaluate the effect of different doses with regard toxicopathological changes in rat ingested CuSO4.5H2O The study was done on (66) female rats of approximately the same age and body weight. The first experiment was done on (30) rats, the animals were divided into (5) groups, each group composed of (6) animals ingested toxic doses of CuSO4.5H2O for studying the symptoms of acute toxicosis, time of appearance and disappearance, and for determination of LD50 by using probit method. The result of the experiment showed that the value of LD50 was 809 mg/kg.bw. The acute toxic signs appeared after short time and become more severe with increasing rate of the death according to the dose of the drug. Second experiment was done on (36) rats divided into (3) groups each groups contain (12) animals as in the followings, First group: Administered orally with distilled water day for (3) months and considered as a control group. Second group: Administered orally (8) mg /kg.b.wday of CuSO4.5H2O for 3 months and considered as Treated 1 group (T1). Third group: Administered orally (40) mg kg.b.w day of CuSO4.5H2O for 3 months and considered as Treated Two group (T2). The clinical signs were checked continously. The main signs were anorexia, decrease in body weight ,the mucous membranes were paleyellow, with rough skin, ruffled hair and alopecia especially in the abdominal regoin, hemaglobinurea and dyspnea. The severity of signs increased with high dose and long duration Toxicopathological changes due to CuSO4.5H2O showed the followings. The gross lesions of liver characterized by hepatomegaly or atrophy with pale- yellow color. Kidney darkish brown descolaration (gunmetal) colored with presence of small whitish nodules in high dose group, splenomegaly due to congestion or atrophy and fibrosis. The brain showed congestion and edema, with thickening of the stomach wall and catarrhal enteritis. The microscopic examination showed that the severity of the lesions depend upon the dose and duration of treatment. The liver undergo fatty degenerations with centri-lobular necrosis which was a constant feature of all examined sections, with focal infiltration of mononuclear cells, with apoptosis, severe hemorrhage with formation of hyperplastic nodules and deposition of hemosiderin pigment in hepatocytes, proliferated kupffer cells and periportal fibrosis. The lesions of the kidney were characterized by degeneration and necrosis of the epithelial lining of the proximal convoluted tubules with deposition of hemosiderin pigment and dilation of cortical and medullary renal tubules with formation of hyaline cast , cortical tubular basophilia and interstitial infiltration of mononuclear cells and fibrosis of medullary region especially in high dose.The brain sections showed perineuronal and perivascular edema with focal gliosis and demyelination with focal aggregation of microglial cells around the blood vessels with hemorrhage especially in high dose. The heart lesions were represented by fatty degeneration and myocarditis and epeicarditis with infiltration of mononuclear cells and areas of necrosis and hemorrhages with fibrosis in high dosage group. Spleen showed severe depletion of white pulp lymphoid tissue with extramedullary 2 hemopoiesis characterized by the presence of large numbers of megakaryocytes, severe congestion and deposition of hemosiderin pigment and fibrosis especially in high dosage group, the non-glandular stomach showed hyperplasia and hyperkeratosis. Bone sections showed suppression of hempoietic tissue with signs of osteoporosis. The study have been concluded that CuSO4.5H2O poisoning in rat causes toxicopathological changes internal abdominal organs with precancerous lesions