A single injection of cadmium chloride (3.75 mg/kg) was made into the peritoneal cavities of albino rats. The cortices of kidney were obtained from the experimental animals at 3 hr., 6 hr., 12 hr., 24 hr. and 36 hr. after administration of cadmium chloride, respectively. The specimens of each experimental animal were prefixed in 2% glutaraldehyde-4% paraformaldehyde solution for $2{\sim}4$ hours, and these specimens were post-fixed in 1% osmic acid. After fixation, the specimens were dehydrated with alcohol and acetate and embedded in Epon 812. Ultrathin sections, $600{\sim}800{\AA}$ thickness were made and stained with uranyl acetate and lead citrate. And all the preparations were observed with Hitachi-600 transmission electron microscope. The results obtained were as follows: 1. The main changes in ultrastructures of the glomeruli observed at 3 hr. after cadmium chloride administration include loss of filtration slit and fenestrae of capillary endothelium that was resulted from thickings of the basal lamina and fusion of pedicels of the podocytes. At 12 hr. after cadmium chloride administration the Bowman's capsules were mostly filled with abnormally thickened and fused pedicels. After 24 hr. however, the only recognized change was loss of fenestrae of the capillary endothelium. And the ultrastructure of the glomeruli were almost normal in 36 hr. after cadmium chloride treatment. 2. At 3 hr. after treatment with cadmium chloride, in the renal tubular cells the vesicles and vacuoles increased in number at the apical portion, of the tubular epithelial cells, the basal infoldings were reduced and the basal lamina was thickened. After 12 hr., a number of phagosomes appeared at the apical portion and the cisternae of rough endoplasmic reticulum were swollen. At 24 hr. after cadmium chloride administration irregularly shaped mitochondria were observed in the apical area, and mitochondria with swollen cristae were found at the basal portion. And after 36 hr. The ultrastructures of the epithelial cells appeared almost normal except for a moderate increase in the number of vesicles and vacuoles. Consequently it is suggested that in albino rats, cadmium chloride induces acute reversible degenerative changes in the glomeruli as well as in the epithelial cells of the proximal convoluted tubules.
This study investigated the localization and changes in the concentration of injected mercury in the kidney, liver, and spleen of mice. To evaluate changes in the concentration of mercury over time, the mice were euthanized 10, 150, and 300 days post-treatment. Localization of accumulated mercury was identified by the autometallography method. Mercury was densely located in the supranuclear cytoplasm of epithelial cells of proximal tubules of the kidney but was not detected in the glomerulus 10 days post-treatment. In the liver, mercury was mainly found in hepatocytes around the portal vein and in sinusoidal Kupffer cells 10 days post-treatment. Mercury was scattered throughout both white and red pulp of the spleen 10 days post-treatment. In terms of changes in the concentration of mercury, the levels were lower in the renal cortex and medulla 150 and 300 days post-treatment as compared with those 10 days post-treatment. Mercury was found at low concentrations in liver hepatocytes 150 and 300 days post-treatment. The mercury concentration was also low in both the white and red pulp of the spleen 150 and 300 days post-treatment. Therefore, the concentrations of accumulated mercury in the kidney, liver, and spleen 150 and 300 days post-treatment were lower than those 10 days post-treatment. We identified the localization of mercury in cells and tissues of several organs and observed that accumulated mercury in organs decreased naturally over time.
This study were carried out to investigate cytotoxicity of paraquat and bentazon that is scattering to farm products were essensial for human diet and compensatory effects of 3-methylcholanthrene (3-MC) in vitro and in vivo. In vitro, The 5.0$\times$$10^4$ cell/ml of NIH 3T3 fibroblast in each well of 24 multidish were cultured. After 24 hours, the cells were treated with solution of paraquat and bentazon (1, 25, 50, 100 pM respectively). After the NIH 3T3 fibroblast of all groups were cultured in same condition for 48 hours, Sulfohordamin B Protein (SRB) assay were performed to evaluate the cytotoxicity of cell organelles. Paraquat and bentazon $SRB_50$ were 1860.73 $\mu\textrm{M}$, 1913.38 $\mu$M respectively. In vivo, Sprague Dawley male rats divided into paraquat and bentazon only administered group and simultaneous application group of paraquat and bentazon and 3-MC. At 30 min. and 1, 3, 6, 12, 24, 48 and 96 hrs. interval after each treatment, the animals were sacrificed by decapitation and kidney were immediately removed, immersed in fixatives, and processed with routine method for light microscopic study. Paraffin sections were stained with H-E, PAM, and PAS. Under the light microscope, atrophic change of renal corpuscles were frequently observed from 3 hrs after paraquat and bentazon treatment. The increase of the mesangium was apparent from 12 hrs later after paraquat and bentazon treatment. Necrotic changes of the epithelium and loss of brush border of proximal tubules were most severe at 48 hrs after paraquat and bentazon treatment, respectively. In contrast there were no evidences of the toxic effects on renal tissues at 48hrs in paraquat and bentazon plus 3-MC treated groups.
The effects of aconite root in rats and rabbits were studied following oral administration of the powder which was prepared by lyophilization of the decoction of the salted aconite roots. The $LD_{50}$ of the powder, the blood picture, total blood volume, uptake rate of ${42}^K$ and ${24}^Na$ in various organs, oxygen consumption, thyroid activity, and histopathological changes in various organs, were observed. The results obtained were as follows: 1. The $LD_{50}$ of the powder of decoction of the aconite root was 4.07g/kg of body weight in mice which is equivalent to approximately 40g/kg of the salted aconite roots. 2. The number of erythrocytes and leukocytes, hematocrit value, and the amount of hemoglobin in blood were increased in the rats administered daily dosages of 0.1, 0.5, and 1.0g/kg respectively. No significant differences were observed in the differential count of leukocytes. A slight tendency of hemoconcentration was recognized. 3. No changes in the erythrocyte volume, plasma volume and total blood volume were observed in the rats after administration of the powder for one, three, and six days. However, those were decreased in rats treated for ten days. 4. Generally, in various organs of rats the uptake rate of ${24}^Na$ showed a tendency of increasing but that of ${42}^K$ slowed a decreasing tendency. 5. The oxygen consumption was markedly decreased in rats administered the powder. 6. Iodine-131 uptake of thyroid gland was markedly decreased in the rabbits following administration of the powder. 7. In rabbits administered 0.5g/kg for 20 days, fatty changes of hepatic cells, cloudy swelling of the epithelial cells of proximal convoluted tubules of the kidney and the dilation of splenic sinuses were observed, however, milder changes were found in rabbits treated with 0.1g/kg for the same period.
Park, Woo-Hee;Rhyoo, Moon-Young;Lee, Hyun-kyoung;Choi, Eun-Jin;So, Byung-Jae;Lee, Kyung-Hyun
Korean Journal of Veterinary Service
/
v.38
no.4
/
pp.249-252
/
2015
Primary renal tumors are uncommon in dogs with prevalence rate of approximately 1%. Renal carcinoma originating from epithelium of proximal convoluted tubules are more likely to be affected to Middle-aged dogs (average age, 8y), males about twice as often as bitches. A 10-year-old, female, German Shepherd dog with history of anorexia, vomitting and hematuria was referred to the Animal Disease Diagnostic Division in Animal and Plant Quarantine Agency. The dog was necropsied and several organs were collected, fixed in 10% phosphate-buffered formalin, embedded in paraffin wax and sectioned for histopathology. Grossly, the kidneys were bilaterally enlarged ($18{\times}12{\times}8cm$; left, $18{\times}10{\times}8cm$; right). The numerous cysts varying sizes from 3 to 6 cm in diameter were protruding from the surface of both kidney. A large nodule ($10{\times}6{\times}6cm$) was discovered between cardiac and diaphragmatic lobe in the right lung. Immunohistochemical examination revealed strong positive reaction to cytokeratin and ki-67 in the nuclei of the epithelial tumor cells. But showed negative reactions to vimentin and CD10. Based on the pathological and immunohistochemical examination, we diagnosed as the bilateral renal cystadenocarcinoma in German shepherd dog.
To investigate the defensive effect of green tea against the lead toxicity, Sprague-Dewley rats (150 gm) were divided into 5 groups; the control group (A), the group treated with lead for 4 weeks (Group B-1), the group treated with lead and green tea for 4 weeks (Group B-2), the group treated with lead for 8 weeks (Group C-1), and the group treated with lead and green tea for 8 weeks (Group C-2). The lead acetate (500 ppm) was injected two times for one week into the abdomen and green tea solution (3 g/100 ml distilled water) offered freely. The results of histological and biocheical study are as follows; 1. Blood Urea Nitrogen (BUN) were increased in all the tested groups. The Group B-1 was more increased than the Group B-2, and the Group C-1 more than the Group C-2. The values of Alkaline phosphatase (ALP) were also decreased in all the tested groups, as such the former phenomenon. 2 In the Group B-1, some microvilli, mitochondria and rER were modificated on epithelial cell of proximal renal tubules. The cristae of mitochondria were enlarged, microvilli and nucleus were observed normally on the Group B-2. The number of Microvilli, mitochodria and rER were decreased, many lysosomes and irregular nucleus observed in the Group C-1. In the Group C-2, microvilli were modificated slightly and other organelles were observed similary with the Group B-2.
Park, Sang-Joon;Lee, Sae-Bom;Lee, Young-Ho;Ryu, Si-Yun;Jeong, Kyu-Shik;Lee, Cha-Soo
Korean Journal of Veterinary Pathology
/
v.3
no.1
/
pp.15-25
/
1999
To elucidate the mechanism of age-related development in FGS/NgaKIST mice with spontaneous glomerulosclerotic lesion, we examined expression and localization of various cytokine mRNA in the kidney in the progression of diseases. This mouse model is the first to develop spontanously occuring glomerosclerotic lesion in the kidney. In this study, we detected the up-regulation of local cytokine genes such as IL-1$\beta$, IL-2, IL-6, IL-10, TNF-$\alpha$, TGF-$\beta$, and IFN- $\gamma$ in the kidneys. In RT-PCR and Southern blot analysis, we detected gradual expressions of cytokine mRNA of IL-1$\beta$, IL-2, IL-6, IFN- $\gamma$, and TNF $\alpha$ mRNA during the course of disease. Other cytokines including IL -10 and TGF -$\beta$ were found to be appeared the slightly expressed level at 3 to 12 weeks before onset of inflammatory lesion but they are highly expressed at the end-stage of the disease accompaning high proteinurea and wasting. In situ RT-PCR, each cytokine mRNA were specifically localized in a variety of cells including mesangial, endothelial, parietal epithelial, tubular epithelial, arterial muscle cell, and infiltrated inflammatory cells. In addition, TNF - $\alpha$was detected moderately in the visceral and parietal epithelial cell, but weakly in endothelial and mesangial cells, whereas IL-1 $\beta$ and IL -6 were strong in mesangial regions. IL-6 and TNF- $\alpha$ was highly localized in the damaged proximal and collecting tubules. Especially, TGF -$\beta$ mRNA was highly found in mesangial cells within glomerulus and interstitium during the end-stage of this disease.. These results indicate that pro inflammatory cytokines such as IL-1 $\beta$, IL-2, IL-6, and TNF- $\alpha$ were gradually expressed from the early stage of this disease to the end-stage, and that IL-10 and TGF-$\beta$ may be important in the accumulation of extracellular matrix(ECM) within glomerulus and periglomerular fibrosis in the progression of this disease as well as tissue destruction in end-stage of this disease.
Recently three proteins, playing central roles in the bidirectional transport of urate in renal proximal tubules, were identified: two members of the organic anion transporter (OAT) family, OAT1 and OAT3, and a protein that designated renal urate-anion exchanger (URAT1). Antibodies against these transporters are very important for investigating their expressions and functions. With the cytokine gene as a molecular adjuvant, genetic immunization-based antibody production offers several advantages including high specificity and high recognition to the native protein compared with current methods. We fused high antigenicity fragments of the three transporters to the plasmids pBQAP-TT containing T-cell epitopes and flanking regions from tetanus toxin, respectively. Gene gun immunization with these recombinant plasmids and two other adjuvant plasmids, which express granulocyte/macrophage colony-stimulating factor and FMS-like tyrosine kinase 3 ligand, induced high level immunoglobulin G antibodies, respectively. The native corresponding proteins of URAT1, OAT1 and OAT3, in human kidney can be recognized by their specific antibodies, respectively, with Western blot analysis and immunohistochemistry. Besides, URAT1 expression in Xenopus oocytes can also be recognized by its corresponding antibody with immuno-fluorescence. The successful production of the antibodies has provided an important tool for the study of UA transporters.
Renal failure syndrome in wild mammals is infrequently reported. Muskrat (Ondatra zibethicus) is a medium-sized rodent known to carry many diseases but rarely exhibiting renal failure. A six-month old female muskrat was submitted to our laboratory for pathological diagnosis, and necropsy revealed severe renal damage with sand-like lithiasis in the ureter, renal calculi, and hydronephrosis. All major organs, including the cerebrum, also showed systemic hemorrhage and calcification which may have been due to uremia induced by renal failure. Histopathologically, necrosis and microcalcification were detected in the renal cortex and the medulla, especially in the proximal convoluted tubules and collecting ducts of the kidney. Significant hyalinization of the glomeruli was also observed, and this suggested chronic nephritis. These findings would support mycotoxic effects, particularly on the kidney. Moreover, infiltration of neutrophils and mononuclear cells was observed in the lung and of plasma cells in the spleen. The definitive cause of the toxic effects in this case of muskrat renal failure could be attributed to contaminated food.
The renal function is under regulatory influence of the central nervous system, mainly through activation of sympathetic nerve to the kidney, and it was recently reported that clonidine, an agonist to ${\alpha}_2$-adrenoceptors, induces diuresis and natriuresis when injected directly into a lateral ventricle of the rabbit brain (i.c.v.). This study was undertaken, therefore, to obtain further information as to the role of the central ${\alpha}_2$-adrenoceptors in regulating renal function, by observing the effects of i.c.v. yohimbine, a specific antagonist of adrenoceptors of ${\alpha}_2$-type, on the rabbit renal function, and to elucidate the mechanism involved in it. With 10 ${\mu}g/kg$ i.c.v. of yohimbine sodium excretion transiently increased along with increasing tendency of urine flow, renal plasma flow and glomerular filtration rate. These responses decreased with increasing doses. With 100 and 300 ${\mu}g/kg$ i.c.v. marked antidiuresis and antinatriuresis as well as profound decreases of renal perfusion and glomerular filtration were noted. Systemic blood pressure transiently increased. In reserpinized rabbits, 100 ${\mu}g/kg$ yohimbine i.c.v. did not produce any significant changes in urine flow, sodium excretion as well as in renal hemodynamics. The pressor response was also abolished. In preparations in which one kidney was denervated and the other left intact as control, i.c.v. yohimbine elicited typical antidiuretic antinatriuretic response in the innervated control kidney, whereas the denervated experimental kidney responded with marked diuresis and increases in excretory rates of sodium and potassium and in osmolar clearance in spite of absence of increased filtration and perfusion . Systemic blood pressure responded as in the normal rabbits. These observations indicate that i.c.v. yohimbine affects renal function in dual ways in opposite directions, the first being the antidiuretic antinatriuretic effects which results from decreased renal perfusion and glomerular filtration due to sympathetic activation and which is predominantly expressed in the normal rabbits, and the second less apparent effect being the diuretic and natriuretic action which is not mediated by nerve pathway but brought about by some humoral mechanism and which is effected by decreased sodium reabsorption in the tubules, possibly of the proximal portion.
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