• 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.

• Journal of Korean Academy of Nursing
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• v.27 no.3
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• pp.520-530
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• 1997

Antineoplastic agents may exhibit effects not only in patients therapeutically exposed, but also in health workers who prepare and administer these drugs. This study was done to clarify whether nurses who handle anticancer drugs show signs of drug absorption. The experimental group was 14 nurses handling anticancer drugs at three medical wards of a hospital in J city ; the control group was 12 psychiatric nurses at the same hospital. The test materials were the nurses' 24hr urine specimens, which were concentrated by XAD-2 column chromatograpy. Tester strains were TA98(±S9mix), TA100(±S9 mix), TA1535(±S9 mix) and TA1537(±S9 mix) : the salmonella mammalian microsomal test (Ames test) was used for the urinary mutagenicity assay. The results are summarized as follow : 1. In qualitative analysis of the results, both experimental group and control group showed 15.4% urine toxicity. 2. The experimental group revealed significantly higher urinary mutagenicity both in the activation method test and non-activation method test of the tester strains TA98, TA100 and TA1535. In the case of TA1537, the two groups showed no difference in the non-activation method test, but the activation method revealed a difference. 3. In urinary mutagenicity of the experimental group by ward career, there was a significant difference between the group with more than 20 months experience and the group with less than 20 months on the tester strains TA98, TA100, and TA1537. No Significant difference was found between two groups by the tester strain TA1535.

• Journal of Nutrition and Health
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• v.21 no.6
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• pp.410-420
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• 1988

This study were performed to investigate effect of dietary cadmium(Cd) and protein levels on growth, body protein metabolism and Cd toxicity in growing rats. Forty eight male rats of Sprague-Dawley weighing 113$\pm$2g were blocked into 6 groups accoridng to body weight. Dietary protein were given at the levels of 7, 15 and 40% of diet and Cd (200ppm)were either added or not. The result obtained were summerized as follow; 1) Food intake, weight gain, FER PER, liver and kidney weight, weight and length of bones, hematocrit, and hemoglobin content in Cd-added groups were low than those in Cd-free groups. 2) Serum total protein showed no significant difference with Cd addition, but it was significantly lower in low protein diet groups. Liver protein in Cd-added groups was lower than Cd-free groups, and was tend to be increased with increasing dietary protein level. 3) Daily urinary and fecal nitrogen excretions in Cd-added groups were lower than Cd-free groups, and were increased with increasing dietary protein level. 4) Cadmium contents in blood, liver, kidney, and femur were tend to be decreased with increasing dietary protein level. Especially, Cd content in kidney of Cd-added groups was significantly decreased with increasing dietary protein level. 5) Daily urinary and fecal Cd excretions were tend to be increased with increasing dietary protein level, and Cd-added-high protein diet group showed the highest Cd excretion among the Cd-added groups, Cd absorption ration and Cd retention ratio were tend to be decreased with increasing dietary protein level.

• 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.

• Nutrition Research and Practice
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• v.3 no.1
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• pp.15-22
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• 2009

This study was performed to investigate the effect of chlorella on cadmium (Cd) toxicity in Cd-administered rats. Sixty male Sprague-Dawley rats (14 week-old) were blocked into 6 groups. Cadmium chloride was given at levels of 0 or 325 mg (Cd: 0, 160 ppm), and chlorella powder at levels of 0, 3 and 5%. Cadmium was accumulated in blood and tissues (liver, kidney and small intestine) in the Cd-exposed groups, while the accumulation of Cd was decreased in the Cd-exposed chlorella groups. Fecal and urinary Cd excretions were remarkably increased in Cd-exposed chlorella groups. Thus, cadmium retention ratio and absorption rate were decreased in the Cd exposed chlorella groups. Urinary and serum creatinine, and creatinine clearance were not changed in experimental animals. In addition, metallothionein (MT) synthesis in tissues was increased by Cd administration. The Cd-exposed chlorella groups indicated lower MT concentration compared to the Cd-exposed groups. Moreover, glomerular filtration rate (GFR) was not changed by dietary chI orella and Cd administration. According to the results above, this study could suggest that Cd toxicity can be alleviated by increasing Cd excretion through feces. Therefore, when exposed to Cd, chlorella is an appropriate source which counteracts heavy metal poisoning, to decrease the damage of tissues by decreasing cadmium absorption.

• Biomolecules & Therapeutics
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• v.4 no.2
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• pp.138-147
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• 1996

DWP401, a recombinant human epidermal growth factor, was subcutaneously administered to ICR mice at the dose levels of 0, 0.04, 0.2 and 1.0 mg/kg/day (15rats/sex/group) in order to evaluate the subchronic toxicity. General observations, examinations for food and water consumption, ophthalmoscopy and urinalysis were carried out during the study. For the complete gross and microscopic examinations, 10 mice/ sex/group were sacrificed at the ends of the dosing period, and the remaining animals were sacrificed with a 5 week recovery period. Examinations for hematology and blood biochemistry were also carried out at the time of recovery period. Based on the results, it was thought that the target tissue or organs were mesothelial cell, injection site, spleen, adrenal gland, ovary and transitional epithelial cell of urinary tract, and no observed toxic level of DWP401 was 0.04 mg/kg while definite toxic dose level might be 0.2 mg/kg.

• Toxicological Research
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• v.14 no.3
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• pp.365-370
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• 1998

To evaluate the renal toxicity of the antitumor agent, p-{N,N,-Bis(2-chloroethyl)amino}-4-phenyl acetyl-amino-2,6-piperidinedione(CK-15), rats were treated with CK-15 (acute: 50mg/kg. i.p., single and subacute: 5mg/kg, i.p., daily for 7 days). The changes in the body weight, water consumption, kidney weights and urine volume after and during the treatment were observed. The concentrations of urinary creatinine and portein, the activities of N-acetyl-${\beta}$-D-glucosaminidase (NAG), alanine aminopeptidase (AAP), ${\gamma}$-glutamyl transpeptidase (${\gamma}$-GT) and lactate dehydrogenase (LDH) in 24hr urine were also determined. The body weight, water consumption, and urine volume were decreased after the acute and subacute administration. However the weights of kidney were not changed after the treatments. The excretion of creatinine was significantly decreased 1 day after acute administration but, returned to the control value. In subactute administration, the excretion of creatinine was gradually decreased. However, the protein excretion did not changed in both treatment. Those indicate that CK-15 might decrease the metabolic rate of muscle. THe urinary activities of NAG, AAP, ${\gamma}$-GT, and LDH were significantly affected bythe drug treatment. The urinary activities of NAG, AAP and ${\gamma}$-GT were significantly increased 1 day after the acute administration and then returned to the control value. However, the urinary activities of LDH were not changed in acute treatment. In subacute treatment, although the urinary activities of NAG were not changed, those of AAP and ${\gamma}$-GT were significantly increased 2.3 times at 3 days during the subacute administration. Also the urinary activities of LDH were significantly increased at 7 day after the administration. These results indicate that the high and subacute administration might induce a damage in the kidney cells. Furthermore the present results suggest that the toxic effects of CK-15 might be due to the accumulation of the metabolites.

• Korean Journal of Medicinal Crop Science
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• v.27 no.3
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• pp.173-185
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• 2019

Background: Galgeun-tang used in traditional Korean medicine, is a mixture of the medicinal plants Cinnamomi Ramulus, Ephedrae Herba and Puerariae Radix, and has been prescribed for the treatment of various ailments, including fever. Although the use of traditional medicinal herbs to treat diseases has recently increased, their safety and toxicity profiles incompletely elucidated. Thus, we evaluated Galgeun-tang's toxicity in male and female Sprague-Dawley rats. Methods and Results: Galgeun-tang (1,000, 2,000 and 4,000 mg/kg) was orally administered to rats for 13 weeks, and then, they were maintained for 4 weeks without administration (recovery period). Their clinical signs, and hematological and urinary properties, were monitored. The results showed that Galgeun-tang administeration slightly increased serum creatinine, urea nitrogen and, aspartate aminotransferase levels. Additionally, 2,000 and 4,000 mg/kg Galgeun-tang significantly increased urinary bilirubn and protein levels of male and female rats, which were restored during the recovery period. Conclusions: The no-observed-adverse-effect level of orally administered Galgeun-tang was 4,000 mg/kg in both female and male rats, and no target organs were identified. In addition, 400 mg/kg was found to be the no-observed-effect level for toxicity under the study conditions.

• Biomolecules & Therapeutics
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• v.19 no.1
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• pp.38-44
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• 2011

Cisplatin is widely used for various types of cancers. However, its side effects, most notably, renal toxicity often limit its clinical utility. Although previous metabolomic studies reported possible toxicity markers, they used small number of animals and statistical approaches that may not perform best in the presence of intra-group variation. Here, we identified urinary biomarkers associated with renal toxicity induced by cisplatin using NMR-based metabolomics combined with Orthogonal Projections to Latent Structures-Discriminant Analysis (OPLS-DA). Male Sprague-Dawley rats (n=22) were treated with cisplatin (10 mg/kg single dose), and the urines obtained before and after treatment were analyzed by NMR. Multivariable analysis of NMR data presented clear separation between non-treated and treated groups. The OPLS-DA statistical results revealed that 1,3-dimethylurate, taurine, glucose, glycine and branched-chain amino acid (isoleucine, leucine and valine) were significantly elevated in the treated group and that phenylacetylglycine and sarcosine levels were decreased in the treated group. To test the robustness of the approach, we built a prediction model for the toxicity and were able to predict all the unknown samples (n=14) correctly. We believe the proposed NMR-based metabolomics with OPLS-DA approach and the resulting urine markers can be used to augment the currently available blood markers.

• Journal of Nutrition and Health
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• v.29 no.9
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• pp.958-970
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• 1996

This study was performed to investigate the effect of dietary calcium level on cadmium and lead toxicity in rats. Fifty-four male rats of Sprague-Dawely strain weighing 152$\pm$12g were blocked into 9 groups according to body weight, and were raised for 30 days. Nine experimental diets different with cadmium(0%, 0.04%), lead (0%, 0.071%) and calcijm(0.5%, 1.0%, 1.5%) levels were prepared. The results are summarized as follow. Weight gain, F.E.R.(food efficiency ratio), and weights of liver, kidney and femur were lower in cadmium exposed groups than those of heavy metal free groups. Weight gain F.E.R. and ash weight of lead groups were lower than those of heavy metal free groups. But, these were increased with increasing dietary calcium level. Cadmium and lead concentrations in blood, liver, kidney and femur were lower in rats fed 1.5% calcium than 0.5% calcium diet. Fecal cadmium and lead excretions were remarkably increased in 1.5% calcium groups, and cadmium and lead retention rates were decreased in 1.5% calcium groups. Metallothionein concentrations in liver, kidney and small intestine were higher in rats exposed to cadmium and lead. Calcium content in blood, femur and daily urinary and fecal calcium excretion were decreased by cadmium and lead additions, and increased in 1.5% calcium groups. Creatinine clearance were decreased with cadmium administratino and calcium addition. In conclusion, weight gain and organ weights were decreased with cadmium or lead administration. But, cadmium administration was more toxic than lead adminstration. Cadmium or lead toxicity was alleviated by increasing dietary calcium level. Especially, lead toxicity was alleviated in proportion to dietary calcium level.