• 한국환경보건학회지
• /
• 제22권4호
• /
• pp.91-101
• /
• 1996

Exposure indices are important tools which enable scientists to reliably predict and detect exposures to xenobiotics and resultant cell injury. Since the de novo synthesis of stress proteins can be detected early after exposure to some agents, analysis of toxicant-induced changes in gene expression, i.e. alterations in patterns of protein synthesis, may be useful to develop as biomarkers of exposure and toxicity. The acute and chronic effects of cadmium(Cd, $CdCl_2$ 20 mg/kg) on Wistar male rats were evaluated concerning cadmium contents, tissues enzyme activity, HSP expression. The results of the study were as follows: 1. Less cadmium was absorbed through the digestive tracts, but the ratio of contents in renal to hepatic cadmium was higher at 8 weeks after treatment. 2. ALT(alanine aminotransferase), AST(aspartate aminotransferase), glucose, BUN(blood urea nitrogen), creatinine, the key indices of the clinical changes in hepatic and renal function were significantly changed by the cadmium treatment after 1 week in liver, after 4 weeks in kidney. 3. Enhanced synthesis of 70 KDa relative molecular mass proteins were detected in 2 hours after cadmium exposure, with maximum activity occurring at 8~48 hours. Induction of $HSP_{70}$ was evident at proximal tubules and glomeruli in kidney. Testicular cells produced enough HSP to be detected normally. From the above results, it could be concluded that $HSP_{70}$ induction by the cadmium treatment was a rapid reaction to indicate the exposure of xenobiotics.

• Applied Microscopy
• /
• 제21권2호
• /
• pp.76-95
• /
• 1991

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.

• Toxicological Research
• /
• 제30권2호
• /
• pp.99-107
• /
• 2014

Melamine-induced nephrotoxicity is closely associated with crystal formation in the kidney caused by combined exposure to melamine (Mel) and cyanuric acid (CA). However, there are few dosage-finding studies for toxicological evaluation of chronic co-exposure to Mel and CA. The objective of this study was to investigate the possible mechanism by which a Mel and CA mixture lead to renal toxicity in rats. Mel and CA were co-administered to rats via oral gavage for 50 days. Nephrotoxicity was determined by measuring blood urea nitrogen (BUN) and serum creatinine (sCr) levels. Relative kidney weights were significantly increased in rats after co-exposure to Mel+CA (63/6.3 or 630/6.3 mg/kg) mixtures. BUN and sCr levels were significantly increased after Mel and CA co-exposure. Taken together, significant increase in KIM-1, NGAL, and calbindin levels were observed in the urine of rats exposed to Mel+CA (63/6.3 or 630/6.3 mg/kg) compared with the corresponding control group. Histological analysis revealed epithelial degeneration and necrotic cell death in the proximal tubules of the kidney after co-exposure to Mel+CA (63/6.3 or 630/6.3 mg/kg). Our data suggest that Mel-mediated renal toxicity may be influenced by CA concentrations in Mel-contaminated milk or foods.

• 생명과학회지
• /
• 제17권10호
• /
• pp.1347-1353
• /
• 2007

성장과정 중 흰쥐 신장에서 나타나는 복합당질의 변화를 알아보기 위해 18일 태자부터 성체에 이르는 신장을 형태적 관찰과 더불어 9가지 lectin (SBA, DBA, PNA, BSL-1, RCA-1, sWGA, UEA-1, LCA 및 Con A)으로 검색하였다. 신장 발생단계에서 성숙한 신원구조와 함께 미성숙한 구조물 즉 소포와 요관아 등이 생후 14일에 이르기까지 관찰되었으며 생후 21일에 이르러 성체와 유사한 구조적 특성을 보였다. 복합당질의 변화를 보면 사구체에서 RCA-1, LCA및 Con A에 반응을 나타내며 RCA-1 및 LCA는 태자와 신생쥐에서 일시적으로 증가하다 성체에서 관찰되지 않으나 Con A는 성장과 더불어 증가하였다. 근위곡요세관은 UEA-1을 제외한 모든 lectin에 반응하며 DBA, SBA, PNA, BSL-1, RCA-1 및 Con A반응이 성장과 더불어 증가하며 특히 RCA-1과 BSL-1반응이 현저하였다. 이에 비해 sWGA와 LCA반응은 성장과정에 일시적으로 증가하며 성체에 이를수록 감소하였다. 원위곡요세관도 근위곡요세관 유사하게 DBA, SBA, PNA, BSL-1 및 RCA-1반응은 성숙과 함께 증가하나 LCA반응은 성숙과정에 일시적으로 증가하며 성체에서 감소하였다. 집합관에서는 DBA, SBA, PNA, sWGA반응이 성숙과 동시에 증가하나 BSL-1, RCA-1, LCA반응은 미성숙관에서 일시적으로 증가하였다. 이상의 반응으로 보아 신장발생과정에서 형태적 기능적 성숙과 함께 다양한 복합당질의 변화를 보이는데 대체로 성숙에 따라 반응이 증가하는 복합당질군과 미성숙기에 일시적으로 증가하며 성체에서 감소하는 복합당질군으로 대별할 수 있었다. 이러한 출생전후 복합당질의 변화는 신장의 기능적 성숙과정과 연관성을 가지며 발생과정에서 현저한 변화를 나타내는 복합당질은 정상 신장발생에 대한 표지인자로 유용할 것이다.

• 생명과학회지
• /
• 제30권7호
• /
• pp.630-633
• /
• 2020

야생 포유류의 신부전 증후군은 거의 보고가 없다. Muskrat (Ondatra zibethicus)는 중간 크기의 설치류이며 많은 질병을 가지고 있으나, 신부전 증후군은 보고된 바가 없으며, 본 케이스는 병리학적 진단을 위해 6개월령 암컷 사향쥐의 다른 임상증후군 없는 상태로 부검을 실시하였다. 요관, 신장결석과 수진증을 관찰하였고, 결석에 의한 심각한 신장 손상과, 뇌 손상을 포함한 전신 출혈과 석회화가 관찰되었고, 이는 신장 손상으로 인한 요로결석과 장기 손상에 기인한 것이다. 괴사 및 미세석회화는 신장 피질 및 수질에서, 특히 근위 곡 세뇨관 및 신장의 수집관에서 검출되었다. 사구체의 초자양변성이 크게 관찰되었으며 이는 만성 신염을 나타내며. 이러한 소견은 특히 신장에 대한 진균성 독성 효과를 나타내는 것으로 사료된다. 또한, 폐에서 호중구 및 단핵 세포의 침윤이 관찰되었고, 비장에서도 만성 염증세포인 형질세포의 침윤이 관찰되었다. 본 소견에서는 사향쥐 신부전에 따른 사인은 오염된 사료섭취로 의심되는 것으로 판단된다.

• Biomolecules & Therapeutics
• /
• 제31권1호
• /
• pp.97-107
• /
• 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.

• Toxicological Research
• /
• 제13권1_2호
• /
• pp.87-94
• /
• 1997

This study was carried out to investigate toxicity of insecticide carbofuran and compensatory effects of phenobarbital sodium (PB) in vivo and in vitro. Sprague Dawley male rats were used as experimental animals and divided into carbofuran only administered group and simultaneous application group of carbofuran and PB. At 30 rain and 1, 3, 6, 12, 24, 48 and 96 hrs after each treatment, the animals were sacrificed by decapitation. 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. $5.0\times 10^4$ cell/ml of NIH 3T3 fibroblast in each well of 24 multidish were cultured: After 24 hours, the cells were treated with solution of six groups; control group cultured in media only, carbofuran $MTT_50$ or $NR_50$ group cultured in the media containing carbofuran $MTT_50$ or $NR_50$ and four experimental groups cultured in the media containing carbofuran $NR_50$ plus various concentratins of PB. After the NIH 3T3 fibroblast of all groups were cultured in same condition for 48 hours, Tetrazolium MTT (MTT) and NR (neutral red) assay were performed to evaluate the cytotoxicity of cell organelles. Under the light microscope, atrophic change of renal corpuscles were frequently observed in 1 and 2 days after carbofuran treatment. The increase of the mesangium was apparent in 1 and 2 days after carbofuran treatment. Necrotic changes of the epithelium and loss of brush border of proximal tubules were most severe at 2 and 3 days after carbofuran treatment, respectively. In contrast, there were no evidences of the toxic effects on renal tissues at 48hrs in carbofuran-PB treated groups. Carbofuran $MTT_50$ and $NR_50$ were 78$\mu M$, 82.5$\mu M$ respectively. MTT and NR quantities were significantly increased in carbofuran-PB 100$\mu M$ treatment group and carbofuran-PB 100$\mu M$ treatment group. On the basis of these results, it is obvious that PB has compensatory effects against carbofuran toxicity.

• Toxicological Research
• /
• 제17권2호
• /
• pp.123-129
• /
• 2001

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 Korean Journal of Physiology and Pharmacology
• /
• 제5권3호
• /
• pp.223-230
• /
• 2001

Melatonin, a pineal gland hormone, is believed to act as an antioxidant via the stimulation of radical detoxifying enzymes and scavenging of free radicals. In this study, effects of in vitro and in vivo treatments of melatonin on the cisplatin-induced lipid peroxidation, LDH release and plasma creatinine were determined in rabbit renal cortical cells. The level of malondialdehyde (MDA) was assayed as an index of lipid peroxidation and the level of LDH release as an indicator of cellular damage. In in vitro studies, cisplatin increased the levels of MDA and LDH release in a concentration-and time-dependent manner. Melatonin inhibited the cisplatin-induced lipid peroxidation and LDH release in a concentration-dependent manner. The minimal effective concentration of melatonin that significantly reduced the $300\;{\mu}M$ cisplatin-induced lipid peroxidation and LDH release was 1 mM. In in vivo studies, the levels of lipid peroxidation and LDH release in renal cortical cells increased significantly 24 or 48 hours after a single injection of cisplatin (6 mg/kg). When the cisplatin-injected rabbits were pretreated with 10 mg/kg of melatonin, a significant reduction in both lipid peroxidation and LDH release was observed. The plasma creatinine level increased from $0.87{\pm}0.07$ mg/dl in control to $6.33{\pm}0.54$ mg/dl in cisplatin-injected rabbits (P＜0.05). Melatonin partially prevented the increase in serum creatinine level $(1.98{\pm}0.11\;mg/dl)$ by cisplatin (P＜0.05). In the proximal tubules from cisplatin-treated group, tubular cells had microvilli of variable heights. Necrotic debris was seen in tubular lumens. In most of cells, the mitochondria and lysosomes were increased in frequency. The endocytic vacuoles were not prominent and distribution of the brush border was irregular and shortened. These cisplatin-induced morphological changes were moderate in the melatonin-pretreated group. These results suggest that the toxicity of cisplatin is associated with the generation of reactive oxygen free radicals and that melatonin is a powerful antioxidant, which prevents some of the adverse effects of cisplatin.

• 대한약리학회지
• /
• 제21권2호
• /
• pp.119-127
• /
• 1985

신장의 기능은 중추신경계 특히 교감신경계의 큰 영향을 받고 있으므로 ${\alpha}$-adrenoceptor의 길항제로 알려진 yohimbine을 가토의 측뇌실내로 (i.c.v.) 투여하여 신장 기능의 변동을 관찰하였다. Yohimbine 10 ${\mu}g/kg$ i.c.v. 로써 일관성인 Na 배설 증가와 함께 뇨량, 신혈류 및 사구체 여과율의 증가 경향을 볼 수 있었으나, 투여량을 증가시키면 그와 같은 작용은 소실되고 100 ${\mu}g/kg$ 과 300 ${\mu}g/kg$에 있어서는 신혈류 및 사구체 여과율의 심한 감소와 함께 현저한 항이뇨 작용과 Na 배설의 감소가 관찰 되었다. 이때 전신 혈압은 일과성으로 증가를 나타내었다. Reserpine 전처치 가토에 있어서는 100 ${\mu}g/kg$ i.c.v. yohimbine에 의한 항이뇨, Na 배설 감소작용, 신혈류 역학의 감퇴등이 소실되어 유의한 변동을 관찰할 수 없었다. 이때 전신 혈압의 상승도 소실 되었다. 일측 신장 신경을 제거하고 반대측 신장을 대조로 둔 표본에 있어서 yohimbine 100 ${\mu}g/kg$을 측뇌실내로 투여하면 대조신에서는 정상 가토에서와 같은 전형적인 항이뇨 작용이 나타났으나, 제신경(실험)신에 있어서는 신혈류 역학에는 변동이 없으나 Na 및 K 배설과 Cosm 및 뇨량의 유의한 증가를 나타냈다. 이때 신세뇨관에서의 Na 재흡수가 억제되었다. 전신 혈압의 변동은 정상 가토에서와 같이 일과성인 증가를 볼 수 있었다. 이상의 실험으로, 가토 측뇌실내 yohimbine은 신기능에 대하여 두 가지 상반되는 영향을 미치며, 첫째는 교감신경 긴장도의 증가로써 신혈류 및 사구체 여과율을 감소시켜 항이뇨 및 Na 배설 감소를 초래하는 작용과, 둘째는 신경 경로를 통하지 않고, 아마도 humoral factor를 통하여 신세뇨관에서 Na 재흡수를 억제하는 작용이 복합적으로 나타내는 것을 알 수 있었다.