• Toxicological Research
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• v.12 no.1
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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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• v.16 no.1
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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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• v.32 no.1
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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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• v.31 no.3 s.62
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• pp.424-439
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• 1998

Urinary cadmium is used as a sensitive indicator for internal Cd dose, and increased excretion of $N-acetyl-\beta-D-glucosaminidase(NAG)$, $\beta_2-microglobulin(MG)$ and total protein are useful indices for renal dysfunction by chronic exposure to Cd. The target group was 184 inhabitant(82 men and 102 women) in an abandoned mine area known as exposure to low level Cd. The control group was took 160 individuals(64 men and 96 women) in Cd not-exposed area. Urinary Cd concentration was significantly higher in the target group than the control. The geometric mean of urinary Cd for male was $2.56{\mu}g/\ell,\;2.80{\mu}g/g$ creatinine and $2.50{\mu}g/S.G.$ in the target group and $1.19{\mu}g/\ell,\;1.36{\mu}g/g$ creatinine and $1.17{\mu}g/S.G.$ in the control. For female $2.69{\mu}g/\ell,\;3.94{\mu}g/g$ creatinine and $2.63{\mu}g/S.G.$ in the target group and $1.27{\mu}g/\ell,\;1.97{\mu}g/g$ creatinine and $1.25{\mu}g/S.G.$ in the control, respectively. In addition, urinary Cd of the target group had affected by the period of residence and dietary habit for the rice and the vegetables from the target area. These findings suggest the chronic exposure to Cd of the target population. Mean excretion of urinary NAG, $\beta_2-MG$ and total protein were not significant between two groups. In the target group, urinary NAG activity and total protein were significantly correlated with urinary Cd, but $\beta_2-MG$ was not related. Urinary excretion of NAG, $\beta_2-MG$ and total protein were significantly increased in $10\leqq$ than in <2 of urinary Cd level. In $2\sim10$ group of urinary Cd level, the excretion of NAG significantly increased while not showed for $\beta_2-MG$. In present study, urinary excretion of NAG was relatively sensitive than $\beta_2-MG$ in chronic exposure population to low level Cd.

• Proceedings of the Korean Society of Applied Pharmacology
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• 1996.04a
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• pp.213-213
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• 1996

The effects of the anti-tumor agent, SDZ-y2434, on rat kidney were investigated to predict the toxicities of its derivatives and to develope less toxic derivatives. After adjusted in metabolic cages for 5 days, rats were treated SDZ-62434(acute : 25mg/kg, i.p, once and 50mg/kg, i.p., once; subacute ; 10mg/kg, i.p., daily for 7 days). Kidney weights and urine volume during the treatment were observed. Creatinine concentration, protein concentration and the activities of N-acetyl-${\beta}$-D-glucosaminidase (NAG), alanine aminopeptidase (AAP), ${\gamma}$-glutamyl transpeptidase (GGT) and lactate dehydrogenase(LDH) in 24 hr urine were also determined. The kidney weights after the acute and subacute administration didn't show any difference. Urine volume increased 5 days after the acute administration (50mg/kg) and 3 days after the subacute administration. The excretion of creatinine was increased 5 days after the acute (50mg/kg) and subacute administration. However, the protein excretion didn't show any change. NAG acivity declined 7 days after the subacute administration. AAP and GGT activites increased 3 days after the acute administration (50mg/kg) but, returned to the control value. LDH activity showed continuousely high value after the subacute administration. These results indicates that the acute administration of SDZ-62434 might damage on glomerulus and that the subacute administration might be cytotoxic to kidney cells.

• Biomolecules & Therapeutics
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• v.6 no.2
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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.

• Journal of Environmental Health Sciences
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• v.49 no.1
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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.

• Journal of Environmental Health Sciences
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• v.37 no.6
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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.

• Journal of Life Science
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• v.29 no.2
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• pp.265-271
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• 2019

In general, specific gravity (SG) and urinary creatinine (CR) have been used to adjust urinary cadmium (Cd) concentrations. However, the validity of correction methods has been controversial. We compared the two adjustments to evaluate associations between urinary Cd and various renal damage markers and to evaluate the relationship between urinary Cd concentration and renal disease markers, such as estimated glomerular filtration rate (eGFR), in a relatively large general population sample. Among the 1,086 volunteers who were enrolled in this study, 862 healthy volunteers who did not have kidney disease were included in the final analysis. Urinary Cd, malondialdehyde (MDA), and N-acetyl-${\beta}$-D-glucosaminidase (NAG) concentrations were measured, the creatinine-based eGFR was calculated, and the relationships between these markers were subsequently analyzed. This study showed the use of urinary Cd concentration adjusted with SG rather than with urinary creatinine may be appropriate in studies evaluating renal function based on Cd exposure. Urinary Cd concentration adjusted with SG had a positive correlation with urinary MDA levels and a negative correlation with eGFR. This relationship was relatively stronger in women than in men. This study showed that urinary Cd level was associated with decreased eGFR in the general population, and oxidative stress was likely to act as an intermediator in this process. These results suggest that eGFR can be a very good indicator of kidney damage caused by Cd exposure in the general population.

• Toxicological Research
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• v.30 no.4
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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.