• BMB Reports
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• v.36 no.4
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• pp.373-378
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• 2003

Effects of L-arginine and NG-nitro-L-arginine methyl ester (L-NAME) on the renal dysfunction that is induced by cisplatin (CDDP) were investigated. A single dose of CDDP (7.5 mg/kg i.p.) induced renotoxicity, which was manifested by increasing the sensitivity of isolated urinary bladder rings to acetylcholine (ACh), together with a significant elevation of serum urea and creatinine, and a severe decrease in serum albumin. Moreover, renal dysfunction was further confirmed by a significant decrease of enzyme activities, such as glutathione peroxidase, GSH-Px (E.C 1.11.1.9), catalase (E.C 1.11.1.6), as well as a significant increase in lipid peroxides that were measured as malondialdhyde (MDA) in kidney tissue homogenates. The administration of L-arginine (70 mg/kg/d p.o in drinking water 5 d before and 5 d after the CDDP injection) significantly ameliorated the renotoxic effects of CDDP, as judged by restoring the normal responses of isolated bladder rings to Ach, and also by an improvement in a range of renal function indices, which included serum urea and creatinine concentrations and kidney weight. In addition, L-arginine prevents the rise of MDA, as well as a reduction of GSH-Px and catalase activities in kidney tissues homogenates. On the other hand, the administration of L-NAME (4 mg/kg/d p.o) resulted in no protection against renal dysfunction that was induced by CDDP treatment. The findings of this study suggest that L-arginine can attenuate kidney injury that is produced by CDDP treatment. In addition, L-arginine may be a beneficial remedy for CDDP-induced renal toxicity, and could be used to improve the therapeutic index of CDDP.

• Environmental Analysis Health and Toxicology
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• v.25 no.4
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• pp.295-306
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• 2010

Objectives : This study was undertaken to examine the metabolomic changes due to gender and diurnal variation at sampling time and to identify an appropriate time point for urine sampling in epidemiologic studies using metabolomic profiles. Methods : Urine samples were collected twice a day (morning and afternoon) from 20 healthy Korean adults after fasting for 8 hours. The metabolomic assay was investigated using $^1H$ NMR spectroscopy coupled with the principal components analysis (PCA) and partial least squares discriminant analysis (PLS-DA). The metabolites responsible for differentiation between groups were identified through the loading plot of PLS-DA and quantified using Chenomx NMR Suite with a 600 MHz library. Results : Metabolites responsible for differentiation in gender and sampling time were creatinine, trimethyl anine oxide (TMAO), hippurate, mannitol, citrate and acetoacetate. Dimethylamine showed difference only as a factor of diurnal time. The level of creatinine was higher in men compared to women, and the levels of citrate, TMAO, hippurate, mannitol, and acetoacetate were higher in women compared to men. The levels of creatinine, TMAO, hippurate, dimethylamine and mannitol were higher in the morning rather than the afternoon while those of citrate and acetoacetate were higher in the afternoon rather than the morning. Conclusions : Since urinary metabolomic profiles varied by gender and diurnal cycle, urine sampling should be performed at the same time point for all participants in epidemiologic studies using metabolomic profiles.

• Toxicological Research
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• v.28 no.3
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• pp.179-185
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• 2012

Paecilomyces sinclairiis (PS) is known as a functional food or human health supplement. However concerns have been raised about its kidney toxicity. This study was performed to investigate the kidney toxicity of PS by 13 week-oral administration to rats. Blood urea nitrogen (BUN), serum creatinine, and kidney damage biomarkers including beta-2-microglobulin (${\beta}2m$), glutathione S-transferase alpha (GST-${\alpha}$), kidney injury molecule 1 (KIM-1), tissue inhibitor of matrix metalloproteinase 1 (TIMP-1), vascular endothelial growth factor (VEGF), calbindin, clusterin, cystatin C, neutrophil gelatinase-associated lipocalin (NGAL) and osteopontin were measured during or after the treatment of PS. BUN, creatinine and kidney damage biomarkers in serum were not changed by PS. However, kidney cell karyomegaly and tubular hypertrophy were observed dose-dependently with higher severity in males. KIM-1, TIMP-1 and osteopontin in kidney and urine were increased dose dependently in male or at the highest dose in female rats. Increased urinary osteopontin by PS was not recovered at 2 weeks of post-exposure in both genders. Cystatin C in kidney was decreased at all treatment groups but inversely increased in urine. The changes in kidney damage biomarkers were more remarkable in male than female rats. These data indicate that the PS may provoke renal cell damage and glomerular filtration dysfunction in rats with histopathological lesions and change of kidney damage biomarkers in kidney or urine. Kidney and urinary KIM-1 and cystatin C were the most marked indicators, while kidney weight, BUN and creatinine and kidney damage biomarkers in serum were not influenced.

• Korean Journal of Clinical Pharmacy
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• v.30 no.4
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• pp.259-263
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• 2020

Background: Dual-type calcium channel blockers (CCBs), such as efonidipine and cilnidipine, are renoprotective drugs that reportedly reduce proteinuria by dilating afferent and efferent arterioles of the glomerulus. However, studies comparing the effect of dual-type CCB on proteinuria have not been conducted. Therefore, we aimed to compare the effect of dual-type CCB (efonidipine and cilnidipine) usage patterns in hypertensive patients with chronic kidney disease (CKD). Methods: This single-center, retrospective study included 53 patients with CKD who 1) initiated efonidipine or cilnidipine treatment while on a renin-angiotensin system inhibitor and 2) had received efonidipine or cilnidipine for at least one year. We compared usage patterns between the efonidipine and cilnidipine groups during the one-year period and analyzed the following outcomes: urinary protein-to-creatinine ratio, blood pressure, and serum creatinine. Results: The study included 25 patients in the efonidipine group and 28 patients in the cilnidipine group. In both groups, blood pressure and urinary protein-to-creatinine ratios tended to decrease; however, the change during each interval was not significant. Conclusions: In patients with CKD who were on renin-angiotensin system inhibitor therapy, the addition of a dual-type CCB (i.e., efonidipine or cilnidipine) tended to reduce proteinuria; however, the change during each interval was not significant.

• Childhood Kidney Diseases
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• v.3 no.1
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• pp.72-79
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• 1999

Renal scarring associated with vesico-ureteral reflux(VUR) is one of the major causes of end stage renal failure and renal hypertension in children. Urinary ${\beta}_2$-microglobulin(MG) has been suggested as a potential marker for presence of renal tubular damage. This study was designed to evaluate the significance of random urine ${\beta}_2$-MG as a predictor of presence of vesico-ureteral reflux in children with urinary tract infection(UTI). 57 children with urinary tract infection were studied. Patients were devided into two groups; 35($78.9\%$) children have UTI without VUR and 12($21.1\%$) children have UTI and VUR. Beta2-MG and creatinine in random urine sample was measured to decide the excretion ratio(${\beta}_2$-MG/creatinine). Among the 57 children with UTI, 44 children were confirmed by urine culture study and 13 children suspected by compatible clinical feature. Random urine ${\beta}_2$-MG of VUR group ($2.2{\pm}5.91$ mg/L) were significantly higher than that of simple UTI group($0.19{\pm}0.16mg/L$)(P=0.03). The ${\beta}_2$-MG/creatinine ratio of VUR group($32.41{\pm}25.7$) were significantly higher than that of simple UTI group($3.93{\pm}3.44$)(P=0.007). In conclusion, random urine ${\beta}_2$-MG and excretion ratio deserved early predictor of presence of VUR in children with UTI. And this method was more simple and inexpensive than the method of measuring ${\beta}_2$-MG with 24 hour urine collection, so might be a useful screening test for VUR in children with UTI.

• Journal of Environmental Health Sciences
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• v.38 no.2
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• pp.95-104
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• 2012

Objectives: The goal of this study was to investigate the relationships between proximity to an industrial complex and blood lead levels and urinary cadmium levels. Methods: We conducted a questionnaire survey and analyzed blood lead and urinary cadmium levels using Atomic Absorption Spectrometry (AAs). Data was analyzed using logistic regression analysis. All statistical analyses were conducted with SAS software version 9.2. The distance between the residence and an industrial complex was calculated through a Geographical Information System (GIS). Results: A total of 967 residents living near a large petrochemical complex in Ulsan participated. The geometric mean levels of blood lead and urinary cadmium were $1.70{\mu}g/dl$ (male: $1.77{\mu}g/dl$, female: $1.67{\mu}g/dl$), and $0.72{\mu}g/g$ creatinine (male: $0.49{\mu}g/g$ cr. female: $0.89{\mu}g/g$ cr.), respectively. Blood lead and urinary cadmium levels both increased with age and were higher among smokers compared to never smokers. Both significantly showed a decreasing trend with rising income. Results from multiple logistic regression analysis showed that urinary cadmium levels for subjects aged less than 20 years old were negatively associated with distance from the industrial area to the residence. The results, however, indicated that the blood lead levels were positively associated with the distance. Conclusions: The results of this study support that proximity to an industrial complex is related to urinary cadmium values for children. A positive finding with blood lead can be explained by the ambiguity of lead exposure sources in the general environment.

• Journal of Nutrition and Health
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• v.29 no.5
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• pp.507-516
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• 1996

This study was undertaken to estimate seasonal variation of riboflavin status and investigate the relationship between riboflavin intake and its biochemical status in rural women. Dietary intake was measured by determining both 24hr recall method and conventient method. The riboflavin intake was also estimated by food frequency method. Ribofiavin biochemeical status was assessed by erythrocyte glutathione reductase activity coefficient(EGR AC) and urinary riboflavin excretion. All information was repeatly collected in three seasons ; farming season (June), harvest season(October), nonfarming season(February). Mean daily riboflavin intake was below RDA for Koreans in all seasons. Cereal & pulse, vegetable were the primary sources of riboflavin intake and provided above 60% of the total dietary riboflavin intake in all seasons. Riboflavin biochemical status was significantly different among seasons(EGR AC P<0.005, 24hr urinary riboflavin excretion P<0.05), and riboflavin biochemical deficiency was highest in February. The mean values of EGR AC revealed riboflavin deficiency in all seasons. However the mean values of urinary riboflavin excretion were within the normal range except 24hr urinary riboflavin excretion in February. On the basis of EGR AC criteria, 44.7% of subjects were at risk of deficiency in June, 44.7% in October, 81.6% in February. Result of individual riboflavin status assessed by EGR AC or 24hr urinary riboflavin excretion criteria was quite alike. Urinary riboflavin excretion per gram of creatinine underestimated riboflavin deficiency. Significant correlations were observed among biochemical indexes. It also appeared that riboflavin intake measured by food frequency method showed significant correlation with biochemical indexes, especially high correlation with EGR AC (P<0.001). The results indicated that the prevalence of riboflavin deficiency seems to be high among rural women in all seasons and the inadequacy of dietary riboflavin intake was reflected in the abnormalcy of riboflavin biochemical status assessed by EGR, AC. Therefore EGR AC seems to be more sensitive measure of impaired riboflavin status compared to urinary excretion.

• Journal of Environmental Health Sciences
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• v.45 no.6
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• pp.583-593
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• 2019

Objectives: The purpose of this study was to evaluate the relationship between the frequency score of wearing personal protective equipment (PPE) and concentration of urinary organophosphorus pesticide metabolites in farmers. Methods: The study was conducted in Chungcheongnam-do Province of South Korea. We collected urine samples from 308 farmers from September to December 2017 and May to July 2018. Among them, 17 farmers with urinary creatinine levels outside the normal range were excluded. Information on the frequency of wearing PPE was obtained from the farmers through face-to-face survey. Each frequency of wearing for seven types of PPE was converted into a score and expressed as a total score, which was divided into quartiles. Four types of urinary organophosphorus pesticide metabolites were analyzed using a gas chromatography mass selective detector. Multiple linear regression analysis was used to identify concentrations of urinary organophosphorus pesticide metabolites affected by the frequency of wearing PPE. Results: The average frequency score of wearing PPE was 8.0. The quartiles of frequency score of wearing PPE were divided as follows: 1st quartile (≤1), 2nd quartile (1-6), 3rd quartile (6-12), and 4th quartile (>12). Compared with subjects with a low frequency score of wearing PPE (reference), subjects with a high frequency score of wearing PPE (4th quartile) had lower concentrations of urinary diethyl phosphate (DEP) (p<0.01) and dialkyl phosphate (ΣDAP) (p<0.05), which is the sum of dimethyl phosphate (DMP), DEP, dimethyl thiophosphate (DMTP), and diethyl thiophosphate (DETP). Conclusion: Concentrations of urinary organophosphorus pesticide metabolites were associated with frequency score of wearing PPE. Particularly as the frequency score of wearing PPE increased, concentrations of urinary DMP, DEP, DETP, and ΣDAP significantly decreased. The findings of this study can contribute to the management of health effects among farmers working with pesticides.

• Molecular & Cellular Toxicology
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• v.4 no.4
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• pp.360-365
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• 2008

In the last several years, studies on the association of oxidative stress damage with exposure in the work place have been conducted. Xenobiotics create an imbalance of the homeostasis between oxidant molecules and antioxidant defense. By monitoring oxidative stress biomarkers, information was obtained on damages induced by oxidative stress and the toxicity of xenobiotics. In the present study, a Job Exposure Matrix (JEM) was constructed using the data from the Working Environment Measurement (WEM) of painters in the shipyard industry from the past 3 years to assess the exposure status. Additionally, by measuring the concentration of urinary malondialdehyde (MDA), the effect of lipid peroxidation was examined. The subjects consisted of 68 workers who were exposed to mixed organic solvents in the painting process and 25 non-exposure controls. The exposure indices of the exposure groups were significantly different (sprayer: 0.83, touchup: 0.54, assistant: 0.13, P<0.05). The urinary MDA concentration of the exposure group was 48.60${\pm}$ 39.23 ${\mu}mol$/mol creatinine, which was significantly higher than 18.03${\pm}$16.33 ${\mu}mol$/mol creatinine of the control group (P<0.05). From the multiple regression analysis of urinary MDA, the regression coefficient for exposure grade was statistically significant. In future studies, evaluation of the antioxidant levels of subjects should be performed simultaneously with quantitative exposure measurements.

• Safety and Health at Work
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• v.11 no.2
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• pp.235-240
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• 2020

Background: Cadmium exposure may induce chronic intoxication with renal damage. Silver soldering may be a source of cadmium exposure. Methods: We analyzed working environment measurement data and periodic health screening data from a small-scale silver soldering company with ten workers. Concentrations of cadmium in air from working environment measurement data were obtained. Concentrations of blood and urinary cadmium, urine protein, and urine β2-microglobulin (β2M) were obtained. The generalized linear model was used to identify the association between blood and urine cadmium and urine β2M concentrations. Clinical features of chronic cadmium intoxication focused with toxicological renal effects were described. Results: The mean duration of work was 8.5 years (standard deviation [SD] = 6.9, range = 3-20 years). Cadmium concentrations in air were ranged from 0.006 to 0.015 mg/㎥. Blood cadmium concentration was elevated in all ten workers, with a highest level of 34.6 ㎍/L (mean = 21.288 ㎍/L, SD = 11.304, range = 9.641-34.630 ㎍/L). Urinary cadmium concentration was elevated in nine workers, with a highest level of 62.9 ㎍/g Cr (mean = 22.151 ㎍/g creatinine, SD = 19.889, range = 3.228-62.971 ㎍/g creatinine). Urine β2M concentration was elevated in three workers. Urinary cadmium concentration was positively associated with urine protein concentration (beta coefficient = 10.27, 95% confidence interval = [4.36, 16.18]). Other clinical parameters were compatible with renal tubular damage. Conclusion: Cadmium intoxication may occur at quite low air concentrations. Exposure limit may be needed to be lowered.