• 대한한의학방제학회지
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• 제17권2호
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• pp.187-194
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• 2009

The kidney toxicities of WK-38 used for improvement of the vascular diseases, was examined using male and female Sprague-Dawley rats. The male and female rats were divided into 4 groups for intragastrical treatment with doses of 0, 5, 50, and 500 mg/kg/day for 13 weeks, respectively. In all male and female rats treated with WK-38, no mortality and gross pathological findings were shown for 13 weeks. There was substantially no change in body weight in all rats with treatment of WK-38. Urine osmolality as renal functional parameters were not exchanged in all rats treated with WK-38. The renal functional parameters including electrolytes excretory rate, creatinine clearance, and solute-free water reabsorption were significantly augmented on account of increase in urinary volume in female rats treated with WK-38, but not male. In summary, this study demonstrates that WK-38 exhibits no toxicity on kidney in all male and female rats.

• 대한이식학회지
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• 제28권3호
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• pp.165-168
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• 2014

The recipient candidate was a 51-year-old male with end-stage renal disease owing to diabetes mellitus. The initial immunosuppressive regimen included basiliximab for induction and tacrolimus, mycophenolate mofetil, and steroids. Urine output was 413 mL/day on the operative day and 100 mL/day on the postoperative day (POD) 1. There was no definite stenosis of the ureter or vessels. He had anuria on POD 2~4 and he had undergone hemodialysis. His serum creatinine level did not decrease. Therefore, a graft biopsy was performed on POD 4. The pathologic finding was consistent with acute calcineurin inhibitor (CNI) toxicity. There was no evidence of rejection or acute tubular necrosis. Anuria continued on POD 6; therefore, we started sirolimus instead of a CNI based regimen. Graft function was gradually recovered 1 day after reduction of CNI dose and hemodialysis was stopped. The serum creatinine level was normalized on POD 10. He was discharged on POD 21.

• 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 Korean Medical Science
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• 제33권53호
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• pp.298.1-298.10
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• 2018

Background: The renal function of individuals is one of the reasons for the variations in therapeutic response to various drugs. Patients with renal impairment are often exposed to drug toxicity, even with drugs that are usually eliminated by hepatic metabolism. Previous study has reported an increased plasma concentration of indoxyl sulfate and decreased plasma concentration of $4{\beta}$-hydroxy (OH)-cholesterol in stable kidney transplant recipients, implicating indoxyl sulfate as a cytochrome P450 (CYP) inhibiting factor. In this study, we aimed to evaluate the impact of renal impairment severity-dependent accumulation of indoxyl sulfate on hepatic CYP3A activity using metabolic markers. Methods: Sixty-six subjects were enrolled in this study; based on estimated glomerular filtration rate (eGFR), they were classified as having mild, moderate, or severe renal impairment. The plasma concentration of indoxyl sulfate was quantified using liquid chromatography-mass spectrometry (LC-MS). Urinary and plasma markers ($6{\beta}$-OH-cortisol/cortisol, $6{\beta}$-OH-cortisone/cortisone, $4{\beta}$-OH-cholesterol) for hepatic CYP3A activity were quantified using gas chromatography-mass spectrometry (GC-MS). The total plasma concentration of cholesterol was measured using the enzymatic colorimetric assay to calculate the $4{\beta}$-OH-cholesterol/cholesterol ratio. The correlation between variables was assessed using Pearson's correlation test. Results: There was a significant negative correlation between MDRD eGFR and indoxyl sulfate levels. The levels of urinary $6{\beta}$-OH-cortisol/cortisol and $6{\beta}$-OH-cortisone/cortisone as well as plasma $4{\beta}$-OH-cholesterol and $4{\beta}$-OH-cholesterol/cholesterol were not correlated with MDRD eGFR and the plasma concentration of indoxyl sulfate. Conclusion: Hepatic CYP3A activity may not be affected by renal impairment-induced accumulation of plasma indoxyl sulfate.

• 대한한의학방제학회지
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• 제20권1호
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• pp.13-24
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• 2012

Objectives : Yukmijihwang-tang(Wan), a well-known formula for invigorating yin-particular kidney yin, was first recorded in "Xiao er Yao Zheng Zhi Jue", consisting of Radix Rehmanniae Preparata, Fructus Macrocarpii, Rhizoma Dioscoreae Oppositae, Poria, Rhizoma Alismatis and Cortex Moutan Radicis with dose proportion of 8:4:4:3:3:3. Although clinical trials have been lacking, various pharmacological actions for Yukmijihwang-tang has been identified newly using animal models. In addition, it was reported that Yukmijihwang-tang increases structural chromosome aberrations significantly in Chinese hamster lung cells. In this article, it is purposed that new studies for pharmacology and toxicology of Yukmijihwang-tang are reviewed. Insight into new studies of Yukmijihwang-tang at the cellular and animal levels will enhance our understanding of Yukmijihwang-tang against various diseases will provide new tools to diagnose and treat patients. Methods : Recent researches for Yukmijihwang-tang were reviewed and summarized in terms of pharmacological action and toxicity. All sources for review were based on recent studies loaded on data base of web sites such as Science Direct and National Center for Biotechnology Information. Results and Conclusions : Recently, reports showed that YMJ had antiaging effects, antioxidant and free radical scavenging activities, anti-renal hypertension and prevented tumors, and diabetes mellitus. However, there is little information on its safety except general toxicity, acute and sub-chronic oral toxicity, or genotoxicity. In addition, clinical trial for Yukmijihwang-tang was limited even though Yukmijihwang-tang has been used extensively in Korean traditional medicine. Thus, further studies are necessary to focus on safety evaluation and clinical trial for Yukmijihwang-tang.

• 한국한의학연구원논문집
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• 제16권2호
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• pp.143-157
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• 2010

Objectives : The objective of this study was to access the effect of Artemisiae capillaris herba Extracts on the organogenetic reproductive toxicity of New Zealand White rabbits when administered by oral gavage. Methods : Gestational New Zealand White rabbits were dosed from 6 days of gestation to 18 days of gestation. It was conducted in accordance with the recommendations of the KFDA Guideline for Detection of Toxicity to Reproduction for Medicinal Products. In addition, serum AST, ALT, LDH and ALP levels were detected with their necropsy and histopathological observation Results: No significant changes of body weights, gains and food consumption were demonstrated in all dosed groups compared to those of vehicle control group except for 2,000mg/kg-dosing group, which showed significantly increase of body weight compared to that of vehicle control group. Normal gross findings were demonstrated in all tested groups. No significant changes of number of corpora lutea, implantation, implantation rate, number of fetal death, loss rate of post-implantation, number of live youngs at C-section, survival rate of post-implantation, number of male live youngs at C-section, number of female live youngs, sex ratio of live young, external anomalies of live youngs and body weight of live youngs were demonstrated in all dosed groups compared to those of vehicle control group. Although some visceral variations such as thymic reminant in the neck, dilation of renal pelvis, dilated ureter and malpositioned left common carotid artery, no significant changes were demonstrated in all dosed groups compared to that of vehicle control group. Some malformations and variation were demonstrated with retardations. However, no significant changes were demonstrated in all dosed groups compared to that of vehicle control group. In addition, similar ossification numbers were detected in sternebrae, metacarpals, metatarsals, phalanges, cervical vertebrae, and sacral and caudal vertebrae. No Artemisiae capillaris herba Extracts treatment-related changes of serum AST, ALT, LDH and ALP levels were demonstrated in all dosed levels in this study. Conclusions : We could conclude that oral administration of Artemisiae capillaris herba Extracts hasn't an influence on the organogenetic reproductive toxicity.

• Environmental Analysis Health and Toxicology
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• 제6권3_4호
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• pp.105-121
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• 1991

The object of this study is to investigate the toxicity of fenvalerate [(RS)-$\alpha$-cyano-3 -phonoxybenzyl-(RS)-2-(4-ch1orophenyl)-3-methylbutyrate] and the effect of carbaryl on the toxicity of fenvalerate. Rats were treated with fenvalerate (50 mg/kg, 100 mg/kg), carbaryl (50 mg/kg, 100 mg/kg) or mixtures of the two compounds (fenvalerate+carbaryl: 50 mg/kg+50 mg/kg, 50 mg/kg+100 mg/kg) by oral administration for 1~3 weeks. Control groups were treated with corn oil. The experimental results were summarized as follows. 1. LD$_{50}$ values of fenvalerate and carbaryl in male rats were 385 mg/kg and 625 mg/kg respectively. When 50 mg/kg and 100 mg/kg of carbaryl were administratrd, LD$_{50}$values of fenvalerate were 265 mg/kg and 225 mg/kg respectively. 2. Biochemical parameters such as ALT, LDH and glucose in serum were much more increased in the groups treated with mixture than the groups treated with either one of fenvalerate or carbaryl. 3. The groups treated with carbaryl and mixture for 3 weeks, the contents of cytochrome P-450 in the liver were significantly increased. In renal microsomal fractions, however, no significant changes of drug metabolizing enzyme activities were observed. 4. The activities of aniline hydroxylase in hepatic microsomal fractions were increased in the groups treated with fenvalerate and mixture and activity was much more increased in the groups treated with mixture. 5. The activities of ATPase in the groups treated with fenvalerate were decreased than that of groups treated with mixture. TBA values and the activity of glucose-6 -phosphatase in the liver were not significantly changed. 6. In mixture treated groups, the activities of cholinesterase in serum and in the liver were more decreased than those of carbaryl treated groups. The activities of carboxylesterase in serum in the liver were slightly increased in mixture treated groups, but in fenvalerate treated groups, the activities of carboxylesterase were much more increased than those of control groups. 7. As a result of this study, when carbaryl was as the synergist of fenvalerate, carbaryl inhibited the activities of esterases, so the toxicity of fenvalerate was increased.sed.

• Toxicological Research
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• 제28권3호
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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.

• 동의생리병리학회지
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• 제24권2호
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• pp.249-257
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• 2010

Crataegii Fructus is commonly used as a improving digestion, removing retention of food, promoting blood circulation and resolving blood stasis agent in East Asia. Cadmium (Cd) is widely distributed in the environment due to its use in industry. An exposure to Cd causes dysuria, polyuria, chest pain, hepatic and renal tubular diseases. The liver is the most important target organ when considering Cd-induced toxicity because Cd primarily accumulates in the liver. This study investigated the protective effect of Crataegii Fructus water extract against cadmium ($CdCl_2$, Cd)-induced liver toxicity in H4IIE cells, a rat hepatocyte-derived cell line and in rats. Cell viability was significantly reduced in Cd-treated H4IIE cells in a time and concentration-dependent manner. However, Crataegii Fructus water extract (CFE) protected the cells from Cd-induced cytotoxicity via inhibition of PARP cleavage. To induce acute toxicity in rats, Cd (4 mg/kg body weight) was dissolved in normal saline and intravenously injected into rats. The rats then received either a vehicle or silymarin (as a positive control) or CFE (50, 100 mg/kg/day) for 3 days, and were subsequently exposed to a single injection of Cd. Alanine aminotransferase (ALT), aspartate aminotransferase (AST) and lactate dehydrogenase (LDH) were significantly increased by Cd treatment. In contrast, pretreatment with CFE reduced ALT, AST and LDH. In histopathological analysis, CFE reduced the hepatic degenerative regions and the number of degenerative hepatocytes. These are considered as direct evidences that Crataegii Fructus has favorable inhibitory effects on the Cd-intoxicated liver damages. The efficacy of Crataegii Fructus shows slight lower than that of silymarin in the present study.

• 생약학회지
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• 제23권2호
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• pp.89-95
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• 1992

The water extract of Gamidaebo-Tang depressed the lethal toxicity of cis-platin$(45{\mu}M/kg,\;s.c.)$, and mitomycin C (6mg/kg, s.c.). Significant depression of renal toxicity(indicated by an increased blood urea nitrogen value and creatinine value) of cis-platin $(35{\mu}M/kg)\;s.c.)$, was observed in mice treated with Gamidaebo-Tang. In rats treated with mitomycin C and Gamidaebo-Tang, the increased LDH activity and reduced total protein and albumin contents by mitomycin C were significantly depressed. The number of WBC was significantly increased in rats treated with mitomycin C but in the rats treated with mitomycin C and Gamidaebo-Tang, the number of WBC was increased and the hematocrit value and the number of RBC and Hgb were significantly increased in the dose-dependent manner. Therefore, bone marrow toxicity of mitomycin C in the rats treated with Gamidaebo-Tang was depressed. In the end, alleviative effects of the side actions of cis-platin and mitomycin C were acknowledged by combined usage of Gamidaebo-Tang and these anti-neoplastic drugs.