الفهرس 
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Abstract
The aims of the present study were to evaluate the pathologic lesions and the clinopathologic changes associated with lead acetate (PbAc) toxicosis in male albino rats with special focus on the role of antioxidant and/or apoptosis in the pathogenesis of this toxicosis. Ninety nine mature male Albino rats (110-130 of body weight) were used in this study. The study was divided into 2 experiments (Exps. I, II). Exp. I (Gps. 1, 2, 3, 4 and 5) was used to study the pathologic and clinicopathologic changes associated with the acute and chronic toxicosis with lead actetate. Rats of gps. 1, 2, 3, and 4 were intubated daily with PbAc at doses of 700, 1000, 200, or 400 mg/ Kg body weight respectively for 7 days (gps 1 and 2) or 90 days (gps. 3 and 4). Rats of Gp. 5 were kept as a control group. Exp. II (Gps. 6, 7, 8 and 9) was used to study the possible protective effect of zinc sulphate against the intoxication with PbAc. Rats of gps. 6 and 7 were intubated with lead acetate 500 mg/kg body weight by stomach tube daily for ten days. Simultaneously with the PbAc, rats of gp. 7 received zinc sulphate (250 mg/L drinking water) daily for 10 days. Rats of gp. 8 received only zinc sulphate (250 mg/L drinking water) daily for 10 days, while, rats of gp. 9 were kept as a negative control group.
Clinical signs of the acutely intoxicated rats included drowsiness, anorexia, lethargy, weight loss, and polyuria. The most characteristic signs of the chronically intoxicated rats were loss of appetite, weight loss, ruffled hair, and reluctance to move. No significant clinical signs were observed in control rats. In exp. II rats of gps. 6 and 7 experienced anorexia, lethargy, and mild diarrhea. No mortalities were recorded in exp. II. No significant clinical signs were observed in rats of gps. 8 and 9.
The pathologic studies revealed that the target organs of the acute and chronic intoxication with the PbAc were brain, liver, testes and kidneys. On the other hands, other examined organs (lung, heart, spleen, and intestines) were less affected and did not show significant lesions. Renal changes in gps 1 and 2 were bilateral and included degeneration and necrosis of tubular epithelium affecting 20-30% of available proximal convoluted tubules, sloughing of necrotic tubular epithelial cells, tubular ectasia, and infiltrates of few neutrophils. The kidneys of the rats of gps 3 and 4 that were euthanized during the 1st and 2nd months had multifocal areas of moderate interstitial lymphoplasmacytic inflammation with mild cortical interstitial fibrosis that surrounded necrotic tubular structures and glomeruli. The Proximal tubular epithelium at these areas was swollen and vacuolated with nuclear pyknosis (degeneration & necrosis). Some tubules contained homogenous light pink material (hyaline cast) and others were filled with grayish birefringent crystals. Some tubular lumens contained an admixture of pink protein, sloughed epithelial cells, and neutrophils. The renal lesions in the rats euthanized at the 3rd month from gps 3 and 4 had similar lesions to those described above, however, in many rats the renal tubules were lined by flattened to low cuboidal epithelial cells that have amphophilic to basophilic cytoplasm and large, reactive large nuclei karyomegaly, interpreted as tubular regeneration. Large eosinophilic intranuclear inclusions consistent with lead inclusions were present in the kidneys of chronically intoxicated rats.
Testicular lesions of acutely intoxicated rats were mild however, several chronically intoxicated had severe testicular lesions, wherein, approximately 25-50% of available seminnefrous tubules had severe degeneration and necrosis. The affected tubules had irregular shape, very thin necrotic spermatogemic epithelium and their lumens were devoid of spermatozoa. The interstitial tissue was thickened by edema, mild early fibrosis and mild infiltration with lymphocytes, plasma cells, and rare neutrophils. Within the degenerated tubules, occasional spermatogenic cells were separated from the surroundings by a halo, appeared markedly smaller, had pyknotic nuclei, and indistinct cytoplasm (apoptosis). Severe diffuse hepatocellular swelling with marked hepatocellular apoptosis characterized the examined liver sections of the acutely and chronically intoxicated rats. Nuclear karyomegaly with intranuclear lead inclusions were present in the hepatocytes of the chronically infotxicated rats. The brain of the acute and chronic intoxicated rats had severe ischemic neuronal necrosis, mild perivascular edema, with gliosis and occasional mild lymphoplasmacytic meningitis.
A histopathologic scoring system was used to evaluate the lesions in exp. II and reveled no significant difference in the lesions’ severity between the rats intoxicated with PbAc and those intoxicated with PbAc and treated with zinc sulphate.
Rats of gps. 3 and 4 that were euthanized 3 months post-intubation showed a significant decrease in the hemoglobin count, mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), mean corpuscular hemoglobin concentration (MCHC), and the hematocrite when compared to the control rats. A significant decrease in the RBCs count was noticed in the rats of gp.4, but not of gp.3, when compared to their control counterparts.
It was concluded that, apoptosis is an important pathway in the pathogenesis of the intoxication with the PbAc and further studies are needed to determine the specific pro-apoptotic proteins that is enhanced by the PbAc. Modulation of these proteins might decrease or inhibit the toxicity with PbAc and other lead compounds.