• Environmental Analysis Health and Toxicology
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• v.21 no.1 s.52
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• pp.35-43
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• 2006

Reproduction and organ structure of the pale chub, Zacco platypus in Isa stream were investigated by means of histological methods. The results of the study confirmed reproductive abnormality and histopathological features in the pale chub. The gonadosomatic index (GSI) of the fish showed two peak in April and August. In summer season, GSI of the male was about two times of the female's GSI. Monthly variation of the gonadal development was very irregular. From the histological analysis of the organ structure, epidermal atrophy, necrosis and hyperplasia of pigment cell were observed in the skin. Epithelial layer lifting and clubbing of the lamella and bifurcation of the filament were observed in the gill. Also histological changes as congestion, cytoplasmic degeneration of hepatic cell, degeneration of bile duct, glomerular dilatation, degeneration of renal tubule and pycnosis of interstitial cell were identified in the liver and kidney, respectively.

• Journal of Preventive Medicine and Public Health
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• v.29 no.1 s.52
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• pp.43-50
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• 1996

We experienced a case of nephropathy in chronic lead poisoning. The patient was 43-year-old male who has been working in secondary lead smelting plant for 14 years. On admission, blood pressure was 160/90 mmHg and the others were non-specific. In past history, he received chelating agent administration for lead poisoning irregularly and medicated for gout, and the blood lead concentration was $180.0{\mu}g/dl$ on 2 months before admission. Smoking habit has been 1 pack per day for 15 years and drinking habit has been 1 bottle of Soju per day but less flow. In liver function test, AST/ALT were 27/28 IU/l and $\gamma-GT$ was 456 IU/l. In blood test, Hb : 11.5 g/dl, Hct : 34.0% and basophilic stipplings were found in peripheral blood smear. Chest PA was normal and abdominal ultrasonographic finding was non-specific except fatty liver. In the test of lead exposure indices, $PbB:83.0{\mu}g/dl,\;PbU:28.3{\mu}g/l$, and blood ZPP was $300.0{\mu}g/dl$. And in renal function test, BUN : 31.4 mg/dl, blood creatinine : 2.7mg/dl, blood uric acid. 9.1 mg/dl, urinary albumin : 100.0 mg/g creatinine, urinary $\alpha_1-microglobulin$ : 120.5 mg/g creatinine, urinary $\beta_2-microglobulin$ : $183.8{\mu}g/g$ creatinine, and 24 hours urinary creatinine clearance was 31.9 ml/min. The ultrasonoguided renal biopsy showed the global sclerosis of glomerulus, moderate atrophy and loss of tubule, and interstitial fibrosis in light microscopy. There were diffuse losses of brush border of proximal tubule in electronmicroscopy.

• Biomolecules & Therapeutics
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• v.31 no.1
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• pp.97-107
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• 2023

Aristolochic acid (AA), extracted from Aristolochiaceae plants, plays an essential role in traditional herbal medicines and is used for different diseases. However, AA has been found to be nephrotoxic and is known to cause aristolochic acid nephropathy (AAN). AA-induced acute kidney injury (AKI) is a syndrome in AAN with a high morbidity that manifests mitochondrial damage as a key part of its pathological progression. Melatonin primarily serves as a mitochondria-targeted antioxidant. However, its mitochondrial protective role in AA-induced AKI is barely reported. In this study, mice were administrated 2.5 mg/kg AA to induce AKI. Melatonin reduced the increase in Upro and Scr and attenuated the necrosis and atrophy of renal proximal tubules in mice exposed to AA. Melatonin suppressed ROS generation, MDA levels and iNOS expression and increased SOD activities in vivo and in vitro. Intriguingly, the in vivo study revealed that melatonin decreased mitochondrial fragmentation in renal proximal tubular cells and increased ATP levels in kidney tissues in response to AA. In vitro, melatonin restored the mitochondrial membrane potential (MMP) in NRK-52E and HK-2 cells and led to an elevation in ATP levels. Confocal immunofluorescence data showed that puncta containing Mito-tracker and GFP-LC3A/B were reduced, thereby impeding the mitophagy of tubular epithelial cells. Furthermore, melatonin decreased LC3A/B-II expression and increased p62 expression. The apoptosis of tubular epithelial cells induced by AA was decreased. Therefore, our findings revealed that melatonin could prevent AA-induced AKI by attenuating mitochondrial damage, which may provide a potential therapeutic method for renal AA toxicity.

• Childhood Kidney Diseases
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• v.17 no.2
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• pp.92-100
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• 2013

Purpose: To investigate the clinicopathologic effects of cyclosporine A (CsA) in children with diseases characterized by mesangial immunoglobulin A deposits such as immunoglobulin A nephropathy (IgAN) and Henoch-Sch$\ddot{o}$nlein purpura nephritis (HSPN). Methods: We retrospectively reviewed the clinicopathologic outcomes of 54 children (IgAN, 36; HSPN, 18) treated with CsA. The starting dose of CsA was 5 mg/kg per day, and it was administered in 2 divided doses. The degree of proteinuria and pathologic changes in renal biopsies were evaluated before and after CsA treatment. Results: The mean protein to creatinine ratio decreased from $3.7{\pm}1.5$ to $0.6{\pm}0.4$(P <0.001), and 32 (59.2%) children achieved complete remission of proteinuria after 1-year CsA treatment. Among the 54 children, 24 maintained normal renal function and 25 exhibited microscopic hematuria or proteinuria at the end of CsA treatment. In the HSPN group, 3 children whose initial biopsies indicated class IIIb disease showed class II disease on follow-up, and the follow-up biopsies of 2 children who had class II disease indicated the same class II disease. In the IgAN group, cortical tubular atrophy occurred in 1 child, and no child with IgAN had cortical interstitial fibrosis or tubular atrophy after 1-year CsA treatment. No significant complications were found in the children treated with CsA. Conclusion: Our findings indicate that CsA treatment is effective and beneficial in reducing massive proteinuria and preventing progression to end-stage renal failure in children with glomerular diseases characterized by IgA deposits, such as IgAN and HSPN, within 1 year of treatment.

• Childhood Kidney Diseases
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• v.6 no.1
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• pp.75-84
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• 2002

Purpose Acute pyelonephritis of growing kidneys may result in renal scarring. TGF-${\beta}1$, inflammatory cytokine, has been suggested to play an important role in promoting renal scarring through apoptosis, suppression of cellular proliferation and fibrosis. We observed the effects of a potent anti-inflammatory agent, methylprednisolone on apoptosis and renal scarring in experimentally induced acute pyelonephritic weaning rats. Materials and Methods: To induce ascending pyelonephritis a saline solution containing Escherichia coli type ATCC No. 25922, pili- form (107 bacteria/mL) was infused into the bladder through the 16-guage silicone cannula for 48 hours to 102 three-week-old Sprague-Dawley rats (50-60g). Experimental groups were divided into three groups according to the treatment protocols, group I (ceftriaxone only, n=3l), group II (methylprednisolone+ceftriaxone n=28), control group (n=43) was not treated. Histopathologic scores of inflammatory changes, fibrosis and tubular atrophy, the apoptosis index and TGF-${\beta}1$ expression score were observed at post-infection 1 and 3 week. Datas were analysed using ANOVA test and P value below 0.05 was interpreted as significant. Results: The mortality rate ($21.4\%$) of group II was not different to the control group ($41.9\%$) and group I ($32.3\%$). The inflammatory score of group II ($0.8{\pm}0.87$) at week 1 was significantly lower than those of the control group ($2.3{\pm}0.87$) and Group I ($1.7{\pm}0.79$) (P<0.05). Apoptosis index of group II ($2.9{\pm}2.15$) at week 1 was significantly lower than those of the control group ($10.0{\pm}1.95$) and group 1 ($8.3{\pm}2.53$) (P<0.05). TCF-${\beta}1$ expression score of group II ($0.8{\pm}0.72$) at week 1 was significantly lower than those of the control group ($1.9{\pm}0.68$) and group I ($1.8{\pm}0.60$) (P<0.05). The fibrosis score of group II ($1.1{\pm}1.10$) at week 3 was significantly lower than that of the group I ($1.8{\pm}0.83$) (P<0.05) Conclusion: Conclusion Combined treatment with methylprednisolone and ceftriaxone reduced inflammation, fibrosis, apoptosis and TGF-${\beta}1$ expression in acute pyelonephritic weaning rats, compared to ceftriaxone alone. Anti-inflammatory agent supplemented to antibiotics could prevent renal scarring more effectively. (J Korean Soc Pediatr Nephrol 2002 ; 6 : 75-84)

• Applied Microscopy
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• v.39 no.4
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• pp.355-363
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• 2009

The purpose of this study was to demonstrate the effect of Momordica Charantia L. water extracts, one of the natural chelator, on the biochemical and enzyme activity changes in the rats liver and kidney caused by lead acetate. Rat approximately 250 g in weight were grouped into the control, lead acetate treated, and the Momordica Charantia L. boiling water extracts treated after lead acetate groups. Lead acetate (1,000 ppm) and Momordica Charantia L. water extracts (5%, 10%) were delivered drinking water. Serum AST, ALT and BUN were measured, histological alteration of liver and kidney were examined by light microscopy. Momordica Charantia L. extract group was decreased serum AST, ALT and BUN level induced by lead. Optical observations of liver tissue, lead group were observed necrosis of hepatic cells and infiltration of inflammatory cells, but Momordica Charantia L. extract group was observed only slight infiltration of inflammatory cells around the central vein. Optical observations of kidney tissue, lead acetate induced atrophy and necrosis of glomerulus and infiltration of inflammatory cell around renal tubule. For the group treated with Momordica charantia L. extract, the glomerulus was similar to the control, some around the renal tubule was observed infiltration of inflammatory cells. In conclusion, Momordica Charantia L. water extract may protect the lead-induced toxicity on liver and kidney.

• Journal of Periodontal and Implant Science
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• v.30 no.2
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• pp.359-374
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• 2000

Cyclosporine A(CsA) is a widely used immunosuppressant for transplant patients and is also used for the treatment of a wide variety of systemic diseases with immunologic disorders. However, its use is frequently limited because of complications such as nephrotoxicity or gingival hyperplasia. Although several hypotheses have been postulated for CsA-induced gingival hyperplasia, i.e. various cytokine effects of inflammatory cells, existence of plaque or CsA itself, but its pathogenesis is still unclear. For experimental chronic CsA toxicity, salt depletion has been shown to increased susceptibility of rodents to the effects of CsA, and this maneuver facilitates production of arteriolopathy and interstitial fibrosis in kidney that mimic the changes found in human. The purpose of this study was to evaluate pathogenesis of CsA-induced gingival hyperplasia by comparing changes between CsA administration groups of normal standard diet and those of low salt diet group. Specific pathogen-free, 20 to 25 days old(120 to 150 g), male Fisher-344 rats(KIST, Korea), 120 to 150g of body weight, were assigned to four groups of six animals each after one week of adaptation period for powder food. Group 1 received olive oil($300{\mu}l/g\;of\;diet$) with normal standard diet(0.4% of sodium)(NSD). Group 2 received CsA(Cypol-N, Jonggundang, Korea; $300{\mu}g/g\;of\;diet$) with normal standard diet(NSD+CsA). Group 3 received same amount of olive oil with low salt diet(0.05 % of sodium, Teklad Premier, U.S.A.)(LSD). Group 4 received same dose of CsA with low salt diet(LSD+CsA). Rats were pair fed and were sacrificed after six weeks. Renal histologic lesions associated with CsA, consisted of cortical interstitial fibrosis, tubular atrophy and hyalinization of arterioles and the impairment of renal function including increase of serum creatinine and decrease of glomerular filtration rate was more severe in low salt diet group. These were proved as the results of activated of renin-angiotensin system in the kidney by low salt condition. Meanwhile the degree of gingival hyperplasia at incisor and molar tooth was less severe in low salt diet group compared with normal sodium diet group. Hyperplastic gingiva showed mild epithelial hyperplasia and expanded underlyng stroma which consisted of matrix increasement, capillary proliferation and dilatation. While the number and the activation of fibroblasts were increased, inflammatory cells were rare in the stroma. The immunohistochemistry for TGF-${\beta}_1$ in the kidney and gingiva revealed stronger positive in LSD+CsA in kidney but in gingiva of NSD+CsA. These results suggested followings; Gingival hyperplasia can be developed without inflammatory cells infiltration and seemed not induced by CsA by itself. The major role for gingival hyperplasia by CsA would be the secondary effect of TGF-${\beta}$, which maybe upregulated by CsA administration. Low salt diet can attenuate this hyperplasia perhaps by decreasing the activation of $TGF-{\beta}$.

• Toxicological Research
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• v.18 no.1
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• pp.47-57
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• 2002

The subacute oral toxicity of 1-(4-methylpiperazinyl)-3-phenylisoquinoline (CWJ- a-5) was investigated in Sprague-Dawley (SD) rats. Five groups of 5 males and 5 females were orally administered at doses of 0, 37.5, 75, 150 and 200 mg/kg with CWJ-a-5 for 2 weeks. In clinical signs, Salivation was observed in the 75, 150 and 500 mg/kg male and female groups. Loss of fur was observed in the 500 mg/kg male and female group. Body weight were significantly decreased in the 150 and 500 mg/kg male groups and in the 500 mg/kg female group. Food consumption was significantly decreased in the 300 mg/kg male group. In serum biochemistry, total cholesterol and phospholipid were significantly increased in 500 mg/kg male and female group. Aspartate aminotransferase was significantly increased in the 500 mg/kg female group. In histopathological examination, vacuolar degeneration of renal tubules in the kidney, vacuolar degeneration of hepatocytes in the liver vacuolar degeneration of myocytes in the heart, vacuolar degeneration of histiocytes in the spleen and thymus, atrophy of seminiferous tubule and degeneration of germinal epithelium in the testis, vacuolar degeneration of corpus luteum, granulosa cell and theca cell in the ovary were observed in the 150 and 500 mg/kg male and female groups. Based on these results, the no observed adverse effect level (NOAEL) with CWJ-a-5 was considered to be 75 mg/kg and the absolute toxic dose was considered to be 150 mg/kg in this study

• Korean Journal of Ichthyology
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• v.18 no.2
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• pp.87-96
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• 2006

Reproduction and organ system of the oily bitterling, Acheilognathus koreensis in Isa stream were investigated by means of histological methods. Sex ratio was observed 1 : 1 in female to male. The gonadosomatic index (GSI) of the female showed two peak in December and April. The ovipositor length index (OLI) represented irregular change. From the histological analysis of the organ system, epidermal atrophy and hyperplasia of pigment cell were observed in the skin. Epithelial layer lifting of the lamella and bifurcation of the filament were observed in the gill. Also histological changes as congestion, cytoplasmic degeneration of hepatic cell, glomerular dilatation, hyaline droplet degeneration of renal tubule epithelium and pycnosis of interstitial cell were identified in the liver and kidney, respectively.

• Childhood Kidney Diseases
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• v.7 no.2
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• pp.239-244
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• 2003

$^{99m}Tc-MAG3$ Scintigraphic Scan is sensitive at depicting focal parenchymal abnormalities and can be used for the measurement of overall renal function. We experienced a 12-year-old girl presenting with fever and flank pain. On the ultrasonogram and post-voiding delayed image of $^{99m}Tc-MAG3$ scintigraphic scan, severe right cortical atrophy and hydronephrosis with vesicoureteral reflux were detected. We could demonstrate the reflux nephropathy by these two diagnostic work-up without conventional voiding cystourethrography.