• 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.

• Korean Journal of Fisheries and Aquatic Sciences
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• v.44 no.6
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• pp.577-583
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• 2011

In 2007, pet food contaminated with melamine caused hundreds of dogs and cats to develop renal failure all over the world. In 2008, over 294,000 infants consumed infant formula and developed kidney stones in China. Further investigation revealed that fish feed also contained melamine; this raised concerns about melamine residues in edible fish tissues, which could have caused the urinary tract stone epidemic. In Korea, catfish fed with assorted feed that included cuttlefish organs that contained melamine developed whitening syndrome and fell dead in some populations in 2008. This event raised suspicions about the toxicity of melamine and all feeds containing melamine were immediately recalled. In this study, we investigated the rates of melamine accumulation and depletion in muscle and viscera of catfish to propose proper withdrawal periods. One group of catfish was fed a commercially available diet that contained 30, 100 and 300 mg melamine per kg diet for 14 days. To investigate residual melamine contents in muscle and viscera, other experimental groups were fed a melamine free diet after being fed melamine for 7 days. The residual amount of melamine was analyzed by LC-MS/MS. The melamine concentration in muscle was estimated to be 3.7 mg/kg after 6 days of feeding with a diet containing 300 mg melamine/kg. After 2 days of culture with a melamine free diet, the residual melamine was depleted and the concentration had decreased from 1.15 mg/kg to 0.19 mg/kg in the muscle of catfish fed a diet containing 300 mg melamine/kg for 7 days. The residual amount of melamine was reduced to 0.03 mg/kg in muscle after 7 days of culture with a melamine free diet and was undetectable after a prolonged culture period of 14 days. Catfish tend to excrete melamine rapidly after oral administration and changes in body color were not observed during the short dosing period.

• Journal of the Korean Society of Food Science and Nutrition
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• v.33 no.5
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• pp.778-784
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• 2004

This study was conducted to investigate the application possibility of leaf and stem extract (LSE) from the mixture of leaf and stem of Panax ginseng. This study measured the general nutritional composition, aminoacid minerals contents and fatty acid composition of LSE. We conducted analysis of the ginsenoside content by HPLC and the cell cytotoxicity tests in normal liver and kidney cells. The approximate composition of LSE was 2.51% of carbohydrate 0.53% of crude ash,0.20% of crude fat and 0.15% of crude protein, respectively. LSE contained 102.56 mg/100 g of K ion and high contents of acidic amino acids such as glutamic acid and aspartic acid. In addition to this, it contained all essential amino acids. The major compositions of fatty acids were 39.99% of palmitic acid 14.96% of linoleic acid, 13.31% of docosatetranoic acid and 12.91% of linolenic acid, The total ginsenoside was 0.82 mg/mL, and ratio of PD/PT was 0.68. Negative effects were not found from the results of the cell toxicity respection. These results imply that leaf and stem of Panax gineng could be used as possible food resources and functional food material and feed stuff.

• Journal of Korean Medical Science
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• v.33 no.53
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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.

• Fisheries and Aquatic Sciences
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• v.24 no.10
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• pp.330-339
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• 2021

Oyster (Crassostrea gigas) is a marine bivalve mollusk widely distributed in coastal areas, and have been long widely used in industrial resources. Several studies demonstrated that fermented oyster (FO) extract attribute to bone health, but whether administration of FO play as an endocrine disruptor has not been studied. Therefore, in the present study, we investigated the effect of FO on the endocrine system in vitro and in vivo. As the results of the competitive estrogen receptor (ER) and androgen receptor (AR) binding affinities, FO was not combined with ER-α, ER-β, and AR. However, 17β-estradiol and testosterone, used as positive control, were interacted with ER and AR, respectively. Meanwhile, oral administration of 100 mg/kg and 200 mg/kg of FO doesn't have any harmful effect on the body weight, androgen-dependent sex accessory organs, estrogen-dependent-sex accessory organs, kidney, and liver in immature rats. In addition, FO supplementation has no effect on the serum levels of luteinizing hormone (LH), follicle stimulating hormone (FSH), testosterone, and 17β-estradiol. However, the relative weight of androgen- and estrogen-dependent organs were significantly increased by subcutaneously injection of 4.0 mg/kg of testosterone propionate (TP) and by orally administration of 1.0 ㎍ of 17α-ethynyl estradiol (EE) in immature male and female rats, respectively. Furthermore, TP and EE administration markedly decreased the serum LH and FSH levels, which are similar those of mature Sprague-Dawley (SD) rat. Furthermore, the testosterone and 17β-estradiol levels were significantly enhanced in TP and EE-treated immature rats. Taken together, our findings showed that FO does not interact with ER and AR, suggesting consequentially FO does not play as a ligand for ER and AR. Furthermore, oral administration of FO did not act as an endocrine disruptor including androgenic activity, estrogenic activity, and abnormal levels of sex hormone, indicating FO may ensure the safety on endocrine system to develop dietary supplement for bone health.

• Journal of Life Science
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• v.31 no.4
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• pp.442-451
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• 2021

Microplastics are fragments of any type of plastic with a size less than 5 mm. Ocean pollution by microplastics is now a worldwide concern in relation to marine ecosystems and human health. The widespread contamination by microplastics means that they can be ingested by and accumulated in diverse species of wildlife, such as fish, mussels, oysters, clams, and scallops. Once ingested, the microplastics can be observed in the intestines, liver, and kidney, and even in the brain. Seafood is one of the major sources of protein intake in humans; therefore, seafood consumption could be pathway for human microplastics exposure. Accumulating evidence indicates that repeated oral exposure to microplastics induces pathologic and functional changes in the reproductive, cardiac, gastrointestinal, endocrine, and even nervous systems of rodents. Maternal exposure to microplastics during gestation and lactation alters metabolic homeostasis in the offspring. Given that seafood provides more than 20% of the total protein intake by over 310 million people worldwide, a reasonable assumption is that microplastics could be substantially accumulated in the human body and impair physiological function. In this review, we have summarized the current status of microplastics contamination in the ocean, their accumulation and toxicities in marine animals and rodents, their exposure to humans, and their potential impacts on human health.

• The Korea Journal of Herbology
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• v.24 no.1
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• pp.89-98
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• 2009

Objectives : The purpose of this study was to evaluate effects of processed sulfur with red ginseng on streptozotocin(STZ) induced diabetic rats for expansion of processed sulfur internal application. Methods : We prepared red ginseng with non processed sulfur extracts(GS), red ginseng with processed sulfur I extracts(GPS I) and red ginseng with processed sulfur II extracts(GPS II). In the present study, we examined about contents of crdue saponin, antioxidant activity, $\alpha$-glucosidase inhibitory activity, and effects of STZ induced diabetic rats. Results : Contents of crude saponin increased by processed sulfur, and GPS II was shown highest contents in crude saponin and sulfur compared with another groups. Electron donating ability of GPS II was shown highest activity compared with GS and GPS I, SOD-like activity showed same tendency as electron donating ability at 1 $mg/m\ell$ concentration. Inhibitory activity of $\alpha$-glucosidase was approximately same level in acarbose and GPS II. Blood glucose level of GPS II group was decreased 18.34% compared with DC(diabetes control) group and maintained stability range in glucose level. but GS and GPS I showed high level compared to GPS II. Serum triglycerides concentration also showed lowest level in GPS II. The activity of ALT, AST and ALP was shown high level in diabetic induced groups, and lowest level in GPS II. Creatinine was shown non-significantly difference in each groups and GPS II was shown lowest level in BUN. Conclusions : These results suggested that processed sulfur with red ginseng have improvement effects on diabetes and internal application of processed sulfur with red ginseng have no specific toxicity in liver and kidney.

• The Korea Journal of Herbology
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• v.24 no.1
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• pp.99-110
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• 2009

Objectives : The current treatment regimens for patients with nephrotic syndrome due to membranous nephropathy(MN) are based on steroids or immunosuppressive therapy with the aim of reducing proteinuria and improving outcome. Although these treatments attenuate the deterioration of renal function in MN patients, it has been suggested that all are burdened by significant toxicity. Therefore, more specific and less toxic therapies are needed. This study was to evaluate the effects of Coptidis Rhizoma Extract(CRE) on the MN induced by cBSA in mice. Methods : Mice were divided into 4 groups. One group named for 'Normal' was injected with a saline solution not to be immunized. The rest groups were treated as follows; After mice were immunized with 0.2 mg of cBSA and Freund's complete adjuvant one time every two weeks for 6 weeks, they received intra-peritoneal injection of 10 mg/kg of cBSA daily for 4 weeks. Also, they were divided into 3 groups. The first named for 'Control' was not given CRE. The second for 'CRE-250' was given oral administration of 250 mg/kg of CRE daily for 4 weeks. The third for 'CRE-500' was given 500 mg/kg of CRE. All of mice were sacrificed 4 weeks after the first immunization. We measured a body weight and 24hrs proteinuria as well as serological analysis. The morphologic changes of renal glomeruli were also observed with a light microscope and an electron microscope. Results : The levels of 24 hrs proteinuria, triglyceride, IgG, IL-6 were significantly decreased in both CRE groups. And the level of IgM was significantly decreased in CRE-250 group. In histological findings of kidney tissue, thickening of GBM and deposition of electron-density were consideraly decreased in both CRE groups. Conclusions : The present study suggests that CRE is highly effective when treating mice with MN induced by cBSA. More clinical data and studies are to be done for efficient application.

• Journal of the Korean Society of Food Science and Nutrition
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• v.40 no.6
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• pp.818-823
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• 2011

Recently, we showed that green tea extract (GTE) markedly lowers the intestinal absorption of $^{14}C$-benzo[a]pyrene ($^{14}C$-BaP) and enhances its secretion into the biliary route, suggesting a protective role for GTE against body burden. These findings indicate that green tea could be used as an effective dietary means against the toxicity of BaP. The present study, therefore, was designed to investigate if green tea intake could affect the tissue distribution and deposition of $^{14}C$-BaP in rats. Male Sprague-Dawley rats had free access to a nutritionally adequate AIN-93G diet and deionized water. At ~340 g of weight, the rats were injected intraperitoneally with 27.4 kBq of [4-$^{14}C$]-BaP and 5.0 mg of BaP dissolved in $300\;{\mu}L$ of olive oil and then assigned randomly to the following two groups: one group (GTE) of rats was fed the AIN-93G diet with GTE via drinking water at approx. 4.7 mg of catechins/d, whereas the other was fed the same diet but without GTE (control). At 4 wk of dietary treatment with GTE, animals were euthanized and heart, liver, brain, spleen, kidney, retroperitoneal fat, testis, and epididymal fat were collected, weighed, and analyzed for tissue $^{14}C$-BaP. Both the control and GTE groups continuously gained weight throughout the study, but there was no significant difference between the groups. No significant differences were observed in the weights of heart, liver, brain, spleen, kidney, retroperitoneal fat, testis, and epididymal fat. However, the radioactivities of $^{14}C$-BaP, expressed in dpm/g, were significantly lower in the heart, liver, brain, spleen, and epididymal fat of rats receiving GTE as compared to their respective controls. These data indicate that green tea intake markedly lowers tissue accumulation of $^{14}C$-BaP. Taken together, these findings suggest that the decreased tissue levels of BaP by GTE intake may be associated with lowered intestinal absorption of BaP and its enhanced secretion into the bile.

• Analytical Science and Technology
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• v.24 no.2
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• pp.69-77
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• 2011

Ethylene glycol (EG) is produced commercially in large amounts and is widely used as antifreeze or deicing solution for cars, boats, and aircraft. EG poisoning occurs in suicide attempts and infrequently, either intentionally through misuse or accidental as EG has a sweet taste. EG has in itself a low toxicity, but is in vivo broken down to higher toxic organic acids which are responsible for extensive cellular damage in various tissues caused principally by the metabolites glycolic acid and oxalic acid. The most conclusive analytical method of diagnosing EG poisoning is determination of EG concentration. However, victims are sometimes admitted at a late stage to hospitals or died during emergency treatment like a gastric lavage or found rotten dead, when blood EG concentrations are low or not detected. Therefore, in this study, the identification of EG was not only performed by gas chromatograpyc-mass spectrometry (GC-MS) following derivatization but also further toxicological analyses of metabolites, glycolic acid (GA) and oxalic acid (OA), were performed by ion chromatography in various biological specimens. A ranges of blood concentrations (3 cases) was $10\sim2,400\;{\mu}g/mL$ for EG, $224\sim1,164\;{\mu}g/mL$ for GA and ND $\sim40\;{\mu}g/mL$ for OA, respectively, In other biological specimens (liver, kidney, bile and pleural fluid), a range of concentrations (3 cases) was ND $\sim55,000\;{\mu}g/mL$ for EG, ND $\sim1,124\;{\mu}g/mL$ for GA and ND $\sim60\;{\mu}g/mL$ for OA, respectively. Liver and kidney tissues were recommended specimens including blood because OA, a final metabolite of EG, was identified large amounts in these despite no detectable EG caused by some therapy.