• Toxicological Research
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• 제16권1호
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• pp.47-52
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• 2000

To evaluate the renal toxicity of the antitumor agent, 1-(N-methyl) piperazinyl-3-phenyl-isoquinoline(CWJ-$\alpha$-5), rats were terated with CWJ-$\alpha$-5 (acute : 100mg/kg, i.p., single and subacute : 10mg/kr, i.p., daily for 7 days). The changes in the body weights, water consumption, kidney weights and urine volume after and during the treatment were observed. The concentrations of urinary creatinine, the activities of N-acetyl-$\beta$-D-glucosaminidase (NAG), alanine aminopeptidase (AAP), $\gamma$-glutamyl transpeptidase ($\gamma$-GT) and lactate dehydrogenase (LDH) in 24 hr urine were also determined. The body weight and water consumption were decreased after the acute and subacute administration. However, the excretion of urine was not changed except the 1 day after the acute treatment. The excretion of creatinine was significantly decreased from 1 day after acute administration and continuously decreased. Also the excretion of creatinine was decreased during subacute administration. However, the protein excretion did not changed in both treatment. Those indicate that CWJ-$\alpha$-5 might decrease the metabolic rate of muscle. The urinary activities of NAG, AAP, $\gamma$-GT, and LDH were significantly affected by the drug treatment. The urinary activities of NAG, AAP and $\gamma$-GT were significantly increased 1 and 3 days after the acute administration and then returned to the control value. However, the urinary activities of LDH were increased 7 days after acute treatment. During subacute treatment, the urinary activities of $\gamma$-GT were not changed. However, the urinary activities of NAG, AAP and LDH were only significantly increased after the third administration. These results indicate that either the high acute dose or the subacute administration with low dose of the compound might induce a temporal damage in the kidney cells.

• Toxicological Research
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• 제12권1호
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• pp.47-52
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• 1996

The renal toxicity of the extract of Polygalae Radix was investigated in rats. Rats were treated with 3.5 mg/Kg of the extract, i.p., for 7 days. Changes in consumatory behavior, 24 hour-urine and the activities of urinary enzymes were determined during the administration of the extract. Significant decrease in body weight and food consumption and increase in 24 hour-urine volume were observed during the administration. However, the quantity of total creatinine in urine was decreased significantly. Those indicate that subacute treatment with the extract might induce diuresis and the ditiresis might be due to the decrease in water reabsorption. In the activities of urinary enzymes, the activities of alanine aminopejotidase (AAP) and gamma-glutamyl transpeptidase (GGT) were increased 4.3 and 3.5 times and then returned to the control. The activity of N-acetyl-${\beta}$-D-glucosaminidase (NAG) was increased 7.2 times and then decreased slowly. But, it was significantly higher than that of the control evea after the last administration. The activity of factate dehydrogenase (LDH) was increased continuozlsly during the treatment. It showed 32 times higher than the control. These results suggested that the extract of Polygalae Radix had toxic effect on kidney. Furthermore, the result suggested that the subacute administration of the extract induced resistance against the toxicity of Polygalae Radix.

• Toxicological Research
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• 제32권1호
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• pp.57-64
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• 2016

Recently several studies reported that the renal toxicity of lead (Pb) and cadmium (Cd) may exist in even a low level exposure. In terms of the deterioration of tubular function, it affects the loss of divalent metals and leads to other complications, so renal tubular effect of heavy metals should be well managed. Considering the exposure to heavy metals in reality, it is hard to find the case that human is exposed to only one heavy metal. We designed a cross-sectional study using Korean Research Project on the Integrated Exposure Assessment (KRIEFS) data to investigate the renal effects of multiple metal exposure in general population. We used blood Pb and urinary Cd as exposure measures, and urinary N-acetyl-${\beta}$-D-glucosaminidase (NAG) and ${\beta}_2$-microglobulin (${\beta}_2$-MG) as renal tubular impairment outcome. We conducted linear regression to identify the association between each heavy metal and urinary NAG and ${\beta}_2$-MG. And then, we conducted linear regression including the interaction term. Of 1953 adults in KRIEFS (2010~2011), the geometric mean of blood Pb and urinary Cd concentration was $2.21{\mu}g/dL$ (geometric $SD=1.49{\mu}g/dL$) and $1.08{\mu}g/g\;cr$ (geometric $SD=1.98{\mu}g/g\;cr$), respectively. In urinary Cd, the strength of the association was also high after adjusting (urinary NAG: ${\beta}=0.44$, p < 0.001; urinary ${\beta}_2$-MG: ${\beta}=0.13$, p = 0.002). Finally, we identified the positive interactions for the two renal biomarkers. The interaction effect of the two heavy metals of ${\beta}_2$-MG was greater than that of NAG. It is very important in public health perspective if the low level exposure to multiple heavy metals has an interaction effect on kidney. More epidemiological studies for the interaction and toxicological studies on the mechanism are needed.

• Journal of Preventive Medicine and Public Health
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• 제31권3호
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• pp.424-439
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• 1998

1995년 8월부터 12월 사이에 미량의 카드뮴에 오염된 것으로 밝혀진 폐광 인근 지역에 거주하고 있는 지역주민 184명(남자: 82명, 여자: 102명)을 대상으로 카드뮴에 의한 만성적인 폭로와 신기능장애를 평가하기 위하여 요중 카드뮴과 NAG활성도, $\beta_2MG$배설량 및 총단백질량을 정량하여 비교 분석하였다. 이때 특별히 카드뮴에 폭로된 적이 없는 일반주민 160명(남자 : 64명, 여자 : 96명)을 대조군으로 선정하였다. 남자의 경우 폭로군의 요중 평균 카드뮴농도는 $2.56{\mu}g/\ell,\;2.80{\mu}g/g$ creatinine 및 $2.50{\mu}g/S.G.$, 대조군은 $1.19{\mu}g/\ell,\;1.36{\mu}g/g$ creatinine 및 $1.17{\mu}g/S.G.$ 였고, 여자에서는 폭로군 $2.69{\mu}g/\ell,\;3.94{\mu}g/g$ creatinine 및 $2.63{\mu}g/S.G.$, 대조군 $1.27{\mu}g/\ell,\;1.97{\mu}g/g$ creatinine 및 $1.25{\mu}g/S.G.$로서 폭로군이 대조군에 비해 남 여 모두에서 유의하게 높았다. 연령에 따른 요중 평균 카드뮴 농도는 남자의 경우 $20\sim39$세군에서는 폭로군과 대조군간에 차이가 없었으나, $40\sim59$세군과 60세 이상군에서는 폭로군이 유의하게 높았다. 여자에서는 폭로군이 대조군에 비해 모든 연령층에서 유의하게 높았다. 또한, 폭로군에 있어서 조사대상 지역에 거주한 기간이 길수록 그리고 이 지역에서 생산된 쌀과 채소류를 섭취하는 사람들의 요중 카드뮴 농도가 높게 나타나, 폐광 인근 지역주민들이 미량이지만 상대적으로 많은 양의 카드뮴에 만성적으로 폭로되고 있는 것으로 추정되었다. 폭로군과 대조군의 요중 평균 NAG활성도, $\beta_2-MG$ 배설량 및 총단백질량은 두 군간에 유의한 차이가 없었다. 그러나, 폭로군에서 요중 NAG활성도와 총단백질량은 요중 카드뮴량과 통계적으로 유의한 정상관이 있었으나 $\beta_2-MG$ 배설량은 유의하지 않았다. 또한 2.0 미만군, 2.0이상 10.0미만군, 10.0이상군으로 구분한 요중 카드뮴 농도수준에 따른 분석시 요중 카드뮴 2.0미만군에 비해 10.0이상군의 NAG활성도, $\beta_2-MG$배설량 및 총단백량이 유의하게 증가되었으며, NAG활성도는 2.0이상 10.0미만군에서도 유의하게 증가되었다. 즉, 폭로군에서 요중 카드뮴 농도에 따른 요중 NAG활성도의 증가가 $\beta_2-MG$배설량의 증가에 비해 상대적으로 민감하게 나타나, 향후 카드뮴 폭로군에 대한 색출검사시 $\beta_2-MG$배설량과 함께 NAG활성도를 조사함으로써 조기진단적 가치가 높을 것으로 사료된다.

• Biomolecules & Therapeutics
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• 제6권2호
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• pp.130-138
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• 1998

In this study, the effect of verapamil (VER) on cyclosporin A (CsA)-induced nephrotoxicity was investigated in uninephrectomized rats. Male Wistar rats were administered CsA (50 mg/kg/day, p.o.) or VER (0.5 mg/kg/day, i.p.) with CsA (50 mg/kg/day, p.o.) for 20 days. The urinary N-acetyl-$\beta$-D-glucosaminidase (NAG) activity along with BUN, serum creatinine, creatinine clearance (CLcr), body weight, and 24 hr-urine output were measured and histopathologic changes of kidney were evaluated by light and electron microscopy. The results obtained from this study can be summarized as follows: While NAG activity, BUN and serum creatinine was progressively increased and CLcr significantly decreased in CsA group, VER almost signifi-cantly (p<0.05) suppressed and normalized CsA-induced changes in VER+CSA group. While urine output increased until 12th days and thereafter progressively decreased in CsA group, it gradually increased in control and VER+CSA group. While body weight progressively made a gain in control and VER+CSA groups, it significantly (p<0.05) lost in CsA group. On light microscopy, the glomerular hyperemia and proximal convoluted tubular (PCT) dilatation, focal tubular cell vacuolation and necrosis were clearly evident in CsA group, but, were not seen in other groups. Ultrastructural studies revealed thickened glomerular endothelium and basal lamina of capillary, irregular shaped pedicels of podocytes, indistinct slit pores and narrowed bowman's space. The large oval vacuoles with dense debris and phagosome were distributed in apical zone and deformed microvilli and mitochondria were seen in the PCT cell of CsA group. But, glomeruli and PCT cell were relatively preserved in normal apperance in other groups. In conclusion, it is suggested that verapamil has a protective effect on cyclosporine-induced nephrotoxicity in uninephrectomized rats.

• 생명과학회지
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• 제29권2호
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• pp.265-271
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• 2019

일반적으로 요중 카드뮴 농도는 요비중 또는 요중 크레아티닌 농도로 보정한 값을 사용해왔다. 그러나 어떤 보정방법이 더 타당한지에 대한 논란은 계속되고 있다. 본 연구에서는 비교적 큰 규모의 일반인구집단을 대상으로 요중 카드뮴농도와 각종 신장손상지표들과의 관련성을 평가함에 있어 요비중 보정 방법과 요중 크레아티닌 보정 방법 중 어느 방법이 더 타당한지 비교 평가하였다. 1,086명의 자원자 중 신장질환의 질병력이 있는 사람을 제외한 862명이 최종적으로 연구대상에 포함되었다. 대상자들로부터 측정한 요중 카드뮴 농도 및 malondialdehyde (MDA), N-acetyl-${\beta}$-D-glucosaminidase 농도, 혈중 크레아티닌을 이용하여 산출한 사구체여과율 등의 신장손상지표들간의 관련성을 평가하였다. 연구 결과, 요중 크레아티닌 농도보다는 요비중으로 보정한 카드뮴 농도가 각종 신장손상지표와 높은 상관성이 있음을 보여주었다. 특히, 요비중 보정 카드뮴 농도는 요중 MDA 농도와 양의 상관관계를, 사구체여과율과는 음의 상관관계를 보여주었다. 이러한 결과는 일반인구집단에서 카드뮴 노출이 많아질수록 사구체여과율이 감소함을 의미하며 이러한 기전에서 산화적스트레스가 관여하고 있음을 보여준다. 또한, 사구체여과율이 카드뮴 노출에 의한 유용한 신장손상지표 중 하나로 사용될 수 있음을 의미한다.

• 한국환경보건학회지
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• 제37권6호
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• pp.450-459
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• 2011

Objectives: Biomarkers in urine are important in assessing exposures to environmental or occupational chemicals and for evaluateing renal function by exposure from these chemicals. Spot urine samples are needed to adjust the concentration of these biomarkers for variations in urine dilution. This study was conducted to evaluate the suitability of adjusting the urinary concentration of cadmium (uCd) and arsenic (uAs) by specific gravity (SG) and urine creatinine (uCr). Methods: We measured the concentrations of blood cadmium (bCd), uCd, uAs, uCr, SG and N-acetyl-${\beta}$-D-glucosaminidase (NAG) activity, which is a sensitive marker of tubular damage by low dose Cd exposure, in spot urine samples collected from 536 individuals. The value of uCd, uAs and NAG were adjusted by SG and uCr. Results: The uCr levels were affected by gender (p < 0.01) and muscle mass (p < 0.01), while SG levels were affected by gender (p < 0.05). Unadjusted uCd and uAs were correlated with SG (uCd: r = 0.365, p < 0.01; uAs: r = 0.488, p < 0.01), uCr (uCd: r = 0.399, p < 0.01; uAs: r = 0.484, p < 0.01). uCd and uAs adjusted by SG were still correlated with SG (uCd: r = 0.360, p < 0.01, uAs: r = 0.483, p < 0.01). uCd and uAs adjusted by uCr and modified uCr ($M_{Cr}$) led to a significant negative correlation with uCr (uCd: r = -0.367, p < 0.01; uAs: r = -0.319, p < 0.01) and $M_{Cr}$ (uCd: r = -0.292, p < 0.01; uAs: r = -0.206, p < 0.01). However, uCd and uAs adjusted by conventional SG ($C_{SG}$) were disappeared from these urinary dilution effects (uCd: r = -0.081; uAs: r = 0.077). Conclusions: $C_{SG}$ adjustment appears to be more appropriate for variations in cadmium and arsenic in spot urine.

• 한국환경보건학회지
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• 제49권1호
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• pp.48-56
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• 2023

Background: Few studies have assessed exposure to chemicals in the context of environmental vulnerability with a focus on exposure among populations living in certain geographical areas. Objectives: This study aimed to investigate cadmium exposure levels and kidney damage indices in environmentally and socioeconomically vulnerable populations, with further subgrouping according to economic status. Methods: Four areas were selected to represent geographical vulnerability (two environmentally vulnerable populations and two socioeconomically vulnerable populations). Among them, population groups with lower socioeconomic status (SES) were separately classified. Urinary cadmium (UCd), beta2-microglobulin (β2-MG), and N-acetyl-β-D-glucosaminidase (NAG) levels were analyzed in samples from 245 residents of these four areas. Results: Geometric means of concentrations of UCd (0.97~2.02 ㎍/g creatinine) in all selected populations (N, 245; mean age, 67.8~70.9 years old) were higher than the national reference values (0.39 for adults and 0.78 ㎍/g creatinine for people in their 60s). Participants with a lower SES had higher UCd and NAG concentrations than did non-low SES participants. In the lower SES group, there was a significant association between UCd and NAG concentrations; however, there was no such correlation in the non-low SES group. Conclusions: Consistent with the findings of previous studies evaluating chemical exposure and associated health effects in specific populations, the findings of this study suggest that individuals with a low SES may be more vulnerable to exposure and related health effects.

• Toxicological Research
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• 제30권4호
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• pp.305-309
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• 2014

Recently, there has been an increase in the use of several nephrotoxicity biomarkers in preclinical experiments. In addition, it has been indicated that the result may have been influenced by secondary factors, such as sample storage condition or storage period. In this study, we have assessed the variation in urinary nephrotoxicity biomarkers as a result of urine storage conditions and storage period of the urine. Urine was sampled from specific pathogen-free Sprague-Dawley rats (19 weeks old), which were housed individually in hanged stainless steel wire mesh cages. Urine was stored at $20^{\circ}C$, at $4^{\circ}C$, or at $-70^{\circ}C$ after sampling. The levels of the biomarkers such as beta-2 microglobulin (B2M), cystatin-C (Cys-C), N-acetyl-${\beta}$-D-glucosaminidase (NAG), micro albumin (MA), micro protein (MP) were measured at 6, 24, 48 and 144 hr after sampling. The B2M level was significantly decreased at 6, 24, 48, and 144 hr compared to 0 hr at $-70^{\circ}C$ (p < 0.05, p < 0.01, p < 0.05, and p < 0.05, respectively) and 24 and 144 hr at $20^{\circ}C$ (p < 0.01, p < 0.01, respectively). The Cys-C level was significantly decreased at 144 hr compared to 0 hr at $4^{\circ}C$ (p < 0.01), at $20^{\circ}C$ (p < 0.05) and at $70^{\circ}C$ (p < 0.01). MP and MA levels were not different for 144 hr in all storage conditions. Taken together, B2M and Cys-C levels were modulated by storage temperature and period. For the enhancement of test accuracy, it is suggested that strict protocols be established for samples to minimize the effects of the storage conditions on the detected levels of biomarkers.