This study was performed to investigate the effect of endotoxin to the CCl4-induced liver injury. Twelve Sprague-Dawley rats were intraperitoneally injected 1.6 g/kg CCl4 as control group. Another 24 rats were orally administrated 300 mg/kg of neomycin at 16 and 3 hours prior to CCl4 injection as experimental group. Twelve among them were intraperitoneally infected 1.0 mg/kg of endotoxin(E-Coli, 0111:B4, No L-2630, lipopolysaccharide, Sigma, USA) and CCl4 simultaneously for offsetting neomycin effect. The rats were sacrificed at 1, 4, 10, and 24 hours after CCl4 injection. The liver tissues from all experimental groups were observed by light and electron microscopy. The results obtained were summarized as follows: In the CCl4 only group, the hepatocytes revealed sweling of ER and mitochondria with many lipid droplet in the cytoplasm. Focal cellular necrosis was seen at the later phase. The Kupffer cells were activated and showed many cytoplasmic processes, secondary lysosomes, and vaculoles. The endothelial cells were edematous. Several neutrophils, platelets, and microthrombi were scattered in the sinusoid. In the neomycin-CCl4-endotoxin administrated group, both hepatocytic destruction and intrasinusoidal microthrombi formation were more pronounced. In the neomycin pretreated group, the hepatocytes revealed mild cellular destruction without necrosis. There is no intrasinusoidal microthrombi. According to these results, it would be concluded that the small dosage of gastrointestinal tract-derived endotoxin affects to the liver injury caused by CCl4. The synergistic effects of CCl4 and gastrointestinal tract-derived endotoxin which can not be detoxified by damaged Kupffer cells, may be more important in the pathogenesis of CCl4-induced liver injury.
Rats ; Animals

This study was carried out to investigate the mechanisms of interstitial pulmonary fibrosis of rats after the intratracheal administration of bleomycin. Both lungs after bleomycin injection were examined by light and electron microscopy. The results are as follows: Light microscopically, 1 or 2 weeks after bleomycin injection acute and chronic inflammatory infiltrates and edema in the interstitium and alveolar spaces were observed. Proliferation of alveolar type II pneumocytes was also found at 4 to 6 weeks after bleomycin injection, chronic inflammatory infiltrates with interstitial fibrous thickening were noted. Electron microscopically, the number of type II pneumocytes and irregular lamellar bodies were increased and blunted microvilli were noted at 2 weeks. 4 to 8 weeks, proliferation of fibroblasts with deposition of abundant collagen fibrils in the thickened interstitium revealing irregular or collapsed alveolar spaces were observed. Based on these findings, it can be concluded that bleomycin-induced interstitial pulmonary fibrosis is considered to pass from an early acute inflammation of the interstitium and alveolar spaces to an interstitial fibroblast proliferation and collagen deposition to the length of the period after injection.
Rats ; Animals

Chronic deposition of uric acid in the kidney can lead to progressive tubulointerstitial injury with granuloma formation. We hypothesized that uric acid crystal deposition may induce granuloma formation by stimulating local expression of macrophage migration inhibitory factor(MIF), which is a known mediator of delayed type hypersensitivity(DTH). A model of acute uric acid nephropathy was induced in rats by the administration of oxonic acid (an inhibitor of uricase) together with uric acid supplements. Kidney tissue examined at 35 days showed widespread tubulointerstitial damage with intratubular uric acid crystals deposition and granuloma formation. Tubules within the areas of granuloma showed a six-fold increase in MIF mRNA compared to uninvolved areas by in situ hybridization. Moreover, the areas of increased MIF mRNA expression correlated with sites of dense accumulation of macrophages and T cells. Control rats fed a normal diet had no discernible evidence of renal disease by routine light microscopy and minimal tubular expression of MIF mRNA and protein. These data suggest that intrarenal granulomas in urate nephropathy may be the consequence of a crystal induced DTH-like reaction mediated by MIF.
Rats ; Animals

Potassium(K+) balance is achieved by the control of urinary K+ excretion and by the control of K+ absorption from the digestive tract. It has been established that chronic potassium depletion is associated with a remarkable hypertrophy of the outer medullary collecting duct of the kidney. But, there are no morphological studies regarding the intercalated cells during the chronic changes of potassium diet. Electron microscopy was performed to observe the morphological alterations of the intercalated cell of the entire collecting duct in response to chronic changes of potassium diet in rat kidney. By electron microscopy, the characteristic features of normal type A intercalated cell of the cortical collecting duct included numerous micro-projections of the apical plasma membrane, complicated basal infolding, apical cytoplasmic tubulovesicles, evenly distributed mitochondia, and centrally located nucleus. In potasium-depleted type A intercalated cell, microprojections of the apical plasma membrane were increased in length and number, basal infoldings were uncomplicated, tubulovesicles were almostly disappeared, and mitochondria were increased in number. Type A intercalated cell of potassium-loading after restriction was found to be almost normal except longer microprojections and increased mitochondria. The characteristic features of normal intercalated cell of the outer medullarycollecting duct(OMCD) included relatively short micro-projections of the apical plasma membrane, uncomplicated basal infoldings, apical cytoplasmic tubulovesicles, and apically distributed mitochondia. In comparison with normal, potassium-depleted intercalated cell of OMCD was hypertrophy, microprojections of the apical plasma membrane were increased in length and number, basal infoldings were complicated, tubulovesicles were almost disappeared, mitochondria were increased in number, and several lysosomes were appeared. Intercalated cell of OMCD of potassium-loading after restriction was found to be almost normal except increased cell size, longer microprojections, and increased mitochondria and lysosomes compared to control. The characteristic features of normal intercalated cell of the inner medullary collecting duct (IMCD) included very short and scant microprojections of the apical plasma membrane, uncomplicated basal infoldings,apica cytoplasmic tubulovesicles, evenly distributed mitochondia, and some lysosomes. In potasium-depleted intercalated cell of IMCD, cell size was prominently increased, microprojections of the apical plasma membrane were increased in length and number, basal infoldings were complicated, tubulovesicles were almostly disappeared, and mitochondria were increased in number. Intercalated cell of IMCD of potassium-loading after restriction was found to be almost normal except increased cell size and increased microprojections in number and length compared to control. These results suggest that intercalated cells adapt through morphological changes to preserve potassium balance during chronic changes of potassium diet.
Rats ; Animals

Diuretics are natriuretic agents which inhibit sodium reabsorption at their major site of action on the renal tubules and increase the excretion of sodium and combined anions. Increment of urine volume is the secondary to the natriuretic effects. Diuretic resistance occurs that threshold dose of diuretics is higher than that of other patients. It is frequently manifested among the edematous patients such as those with the nephrotic syndrome. Prolonged use of diuretics decreases the natriuretic effect of diuretics, which is called diuretic tolerance. This is important adaptations of distal nephron segment. To elucidate the mechanism of diuretic resistance, 1 mg of bumetanide was given to the nephrotic syndrome(NS) patients group and control group, respectively. The peak plasma concentration was delayed in NS patients. The proportion of urine free bumetanide for 24 hours was 73% in NS patients but 100% in control group. The ratio of urine volume and amount of Na+ and Cl - for 24 hours to the total and free urine bumetanide was decreased in NS patients. The study suggests that pharmacokinetic and pharmacodynamic changes of the diuretics induce the diuretic resistance. To determine the additive diuretic effect of albumin to the action of the furosemide, 160 mg of furosemide was administered intravenously with albumin in NS patients. Simultaneous infusion of albumin and furosemide did not enhance the diuretic effect of furosemide pharmacodynamically and pharmacokinetically. Albumin preinfusion 30 minutes before furosemide administration potentiates the diuresis, but natiuresis and pharmacokinetics were not changed. Semiquantitative immunoblotting of rat kidneys was carried out to investigate whether chronic diuretics adminstration induces changes in the abundance of Na+ transporters in distal nephron. Furosemide infusion increased cortical and outer medullary abundances of Na+-Cl- cotransporter(TSC) and all 3 subunits of the epithelial sodium channel(ENaC). Hydrochlorothiazide infusion increased abundances of some kinds of subunits of ENaC. These increases in the abundances of Na+ transporters may account for the generation of diuretic tolerance.These data suggest that to overcome the diuretic resistance or tolerance, diuretic dose increment over the threshold level and more frequent administration of the diuretics are recommended. Diuretic combinations are also proposed. Addition of albumin to augment the diuretics effect ought to be considered cautiously.
Rats ; Animals

In an attempt ultrastructural study of alcohol-induced gastric mucosal change, we selected sixty Sprague-Dawley rats. The rats were administrated with 4 ml of 10% and 40% ethanol enterically and examined by light and electron microscopy. Light microscopically, the thickness of the mucus layer of both 10% and 40% ethanol groups was decreased. The antral mucosa revealed focal inflammatory infiltrates, disturbed glandular arrangements, and significant decrease of mucosal thichness and proper glands. On scanning electron microscopy, flattened or swollen mucosal epithelium and irregularly distributed gastric pits were seen in both experimental groups, and these changes were more severe in the groups of higher concentration and longer duration. On transmission electron microscopy, mitochondrial abnormalities with myelin-like materials and dilatation of endoplasmic reticulum and cytoplasmic blebs were observed. Also the mucus cells show significantly decreased mucus globules, increased fat vacuoles, and large autophagic vacuoles. These alterations were similar to those produced by ethanol in the liver and small intestine. This study indicates that, prolonged administration of ethanol induced chronic gastritis, especially chronic atrophic gastritis.
Rats ; Animals

The purpose of this study is to investigate the morphologic changes of the sinusoidal endothelial cells and the associated structures of the cirrhotic rat liver induced by repeat intraperitoneal injections of N-diethylnitrosamine (DEN) (100 mg/kg/week). One day to 6 weeks later, rat livers were observed under the light, transmission and scanning electron microscopy, and immunostained with laminin antibody. Two weeks after DEN treatment, the fibrillar material in Disse's space was noted, and then a basement membrane-like structure was found at 4 weeks after treatment. Laminin was detected in perisinusoidal areas after 4 weeks. Laminin was strongly positive on the fibrous septum and in the sinusoidal wall of cirrhotic nodules after 6 weeks of treatment. The diameters and numbers of sinusoidal endothelial fenestrations did not change significantly until 2 weeks. They decreased within 4 weeks, and then the sinusoidal endothelium was poorly fenestrated at 6 weeks after DEN treatment. These results suggest that as fibrosis develops in cirrhosis, the deposit of extracellular matrix such as laminin within Disse's space is a major contributing factor in the structural alteration of sinusoidal endothelial cells, and the capillarization of the sinusoidal endothelial cells may be a contributor to impairment of the hepatic function in cirrhosis.
Rats ; Animals

The toxicity and adrenostatic effect of o,p'-DDD, a derivative of the insecticidal DDT, on the adrenal cortex were well known. It known that the toxicity was based on the blocking of steroid biopsynthesis when cholesterol was converted to pregnenolone. Lysodren(R) was also known to be capable of producing a regression of adrenocortical carcinoma and its metastases, and this drug became one of useful choice for the treatment of unoperable adrenocortical carcinomas. Recently, fine structural effect of o,p'-DDD on the adrenocortical carcinoma show that the mitochondria is the primary target organelle. o,p'-DDD was dissolved in corn oil and it was orally administered for 28 days to investigate the ultrastructural effects of zona fasciculata of rat adrenal cortex. The results obtained were as follow: 1) The body weight was decreased after feeding o,p'-DDD. 2) Light microscopic examination showed no remarkable change except increased fine lipid droplets of zona fasciculata in group I (o,p'-DDD 75 mg/kg feeding). Moderately increased intracytoplasmic lipid droplets and pyknotic nuclei bearing membrane indentations were seen in group II (o,p'-DDD 150 mg/kg feeding). Large sized lipid droplet aggregates, pyknotic nuclei with severe nuclear membrane indentations and karyorrhexis in focal area were evident in group III. 3) Immunohistochemical staining for ACTH in pituitary gland showed increasing number of ACTH secretory cell and increasing intensity of staining property according to the dosage of o,p'-DDD. 4) Ultrastructural examination showed increased intracytoplasmic lipid droplets and mild increased peroxisome. There was no remarkable ultrastructural changes in mitochondria in group I. Moderately increased lipid droplets and clusters formation, compressed mitochondria, partial disappearance of mitochondrial cristae, increased peroxisome and nuclear membrane indentations were seen in group II. In group III, nuclear membrane showed prominent indentation. Numberous cytoplasmic vacuolation, double membrane ring in mitochondria, disappearance of mitochondrial cristae, myelin figure formation in mitochondrial matrix, and fatty changes in mitochondrial matrix were seen. These findings showed that the primary target organelle of attack by o,p'-DDD on zona fasciculata of adrenal gland in rat is mitochondria and it was developed from double ring formation in mitochondrial matrix.
Rats ; Animals

No abstract available.
Animals ; Rats*

No abstract available.
Animals ; Rats