• Title/Summary/Keyword: Low Dose Exposure

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The Acute and Chronic Toxicity Effects of Triorganotins on the Growth of Microalgae, Skeletonema costatum (미세조류, Skeletonema costatum의 성장에 미치는 유기주석 화합물들의 급성 및 만성 독성효과)

  • Ham Kyung Hoon;Kim Moo Sang;Lee Hyung Ho
    • Korean Journal of Fisheries and Aquatic Sciences
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    • v.35 no.5
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    • pp.534-541
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    • 2002
  • The use of triorganotins as insecticides, bacteriocides, and antifouling agents has increased dramatically over the past 30 years, In this paper, to evaluate the acute and chronic toxicity effects of various triorganotins (TBTO, TBTE, CTPT, TBTCI) on the growth of microalgae, Skeletonema costatum, we carried out the short term and long term experiments, respectively. In the short-term experiments, the growth of S. costatum was inhibited by the various triorganotins in the dose dependent manners, but recovered by the time laps. The growth inhibition of triorganotins were decreased in the groups with higher initial cell density. These data were resulted from the dilution effect and the biodegradation of triorganotins by the microalgae. In the long-term experiments, S. costatum died completely at the 1 $\mu$g/L of TBTP and CTPT, but didn't in short-term experiments. The facts suggest that the toxicity of the chronic exposure of triorganotins should be increased in the natural sea water with low phytoplankton density.

Role of Glutathione Conjugation in 1-Bromobutane-induced Immunotoxicity in Mice

  • Lee, Sang-Kyu;Lee, Dong-Ju;Jeon, Tae-Won;Ko, Gyu-Sub;Yoo, Se-Hyun;Ha, Hyun-Woo;Kang, Mi-Jeong;Kang, Won-Ku;Kim, Sang-Kyum;Jeong, Tae-Cheon
    • Toxicological Research
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    • v.26 no.2
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    • pp.101-108
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    • 2010
  • Halogenated organic compounds, such as 1-bromobutane (1-BB), have been used as cleaning agents, agents for chemical syntheses or extraction solvents in workplace. In the present study, immunotoxic effects of 1-BB and its conjugation with glutathione (GSH) were investigated in female BALB/c mice. Animals were treated orally with 1-BB at 375, 750 and 1500 mg/kg in corn oil once for dose response or treated orally with 1-BB at 1500 mg/kg for 6, 12, 24 and 48 hr for time course. S-Butyl GSH was identified in spleen by liquid chromatography-electrospray ionization tandem mass spectrometry. Splenic GSH levels were significantly reduced by single treatment with 1-BB. S-Butyl GSH conjugates were detected in spleen from 6 hr after treatment. Oral 1-BB significantly suppressed the antibody response to a T-dependent antigen and the production of splenic intracellular interlukin-2 in response to Con A. Our present results suggest that 1-BB could cause immunotoxicity as well as reduction of splenic GSH content, due to the formation of GSH conjugates in mice. The present results would be useful to understand molecular toxic mechanism of low molecular weight haloalkanes and to develop biological markers for exposure to haloalkanes.

Nicotinamide riboside regulates inflammation and mitochondrial markers in AML12 hepatocytes

  • Lee, Hee Jae;Yang, Soo Jin
    • Nutrition Research and Practice
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    • v.13 no.1
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    • pp.3-10
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    • 2019
  • BACKGROUND/OBJECTIVES: The $NAD^+$ precursor nicotinamide riboside (NR) is a type of vitamin $B_3$ found in cow's milk and yeast-containing food products such as beer. Recent studies suggested that NR prevents hearing loss, high-fat diet-induced obesity, Alzheimer's disease, and mitochondrial myopathy. The objective of this study was to investigate the effects of NR on inflammation and mitochondrial biogenesis in AML12 mouse hepatocytes. MATERIALS/METHODS: A subset of hepatocytes was treated with palmitic acid (PA; $250{\mu}M$) for 48 h to induce hepatocyte steatosis. The hepatocytes were treated with NR ($10{\mu}M$ and 10 mM) for 24 h with and without PA. The cell viability and the levels of sirtuins, inflammatory markers, and mitochondrial markers were analyzed. RESULTS: Cytotoxicity of NR was examined by PrestoBlue assay. Exposure to NR had no effect on cell viability or morphology. Gene expression of sirtuin 1 (Sirt1) and Sirt3 was significantly upregulated by NR in PA-treated hepatocytes. However, Sirt1 activities were increased in hepatocytes treated with low-dose NR. Hepatic pro-inflammatory markers including tumor necrosis factor-alpha and interleukin-6 were decreased in NR-treated cells. NR upregulated anti-inflammatory molecule adiponectin, and, tended to down-regulate hepatokine fetuin-A in PA-treated hepatocytes, suggesting its inverse regulation on these cytokines. NR increased levels of mitochondrial markers including peroxisome proliferator-activated receptor ${\gamma}$ coactivator-$1{\alpha}$, carnitine palmitoyltransferase 1, uncoupling protein 2, transcription factor A, mitochondrial and mitochondrial DNA in PA-treated hepatocytes. CONCLUSIONS: These data demonstrated that NR attenuated hepatic inflammation and increased levels of mitochondrial markers in hepatocytes.

Developing Customized Phantom for Korean Bone Density Using 3D Printing (3D 프린팅을 이용한 한국인 골밀도 맞춤 팬텀 개발)

  • Lee, Junho;Choi, Kwan-Yong;Choi, Jae-Ho
    • Journal of radiological science and technology
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    • v.42 no.3
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    • pp.223-229
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    • 2019
  • In order to reduce the radiation exposure dose of the patient and to obtain accurate diagnosis results, the quality control of the diagnostic radiation generator must be conducted periodically In particular, bone density test equipment could be influenced by many factors, and it is far more important because inaccurate measurement would eventually affect the result value. However, the cross-correction phantom of DXA equipment is poorly penetrated due to lack of awareness of the industry and the high cost. Therefore, this study developed a BMD phantom using a 3D printer and Korean BMD phantom with low cost by cross analyzing Korean BMD value from The Korean National Health and Nutrition Examination Survey and evaluated it. The L1, L2, and L3 BMD values of phantoms produced with the 3D printer were measured to be $0.887{\pm}0.006g/cm^2$, $0.927{\pm}0.006g/cm^2$, and $0.960{\pm}0.005g/cm^2$, at 215 mm height and $0.882{\pm}0.011g/cm^2$, $0.914{\pm}0.005g/cm^2$, $0.933{\pm}0.008g/cm^2$ at 155 mm height displaying statistically significant relevance. The result suggests that a proper quality control and cross calibration of DXA device be possible and expected to be an essential data for various medical phantom manufacture development using 3D printer.

Effects of Nonylphenol on the Secretion of Catecholamines and Adrenocortical Hormones from Short-Term Incubated Rat Adrenal Glands

  • Hee-Su Kim;Yong-Pil Cheon;Sung-Ho Lee
    • Development and Reproduction
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    • v.27 no.4
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    • pp.213-220
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    • 2023
  • Previously, we showed that a chronic-low-dose nonylphenol (NP) exposure resulted in histological changes with sexually dimorphic pattern in rat adrenal glands. We hypothesized that such structural changes are closely related to the hormonal secretory patterns. To test this hypothesis, we developed the short-term adrenal incubation method, and measured the levels of catecholamines and cortical steroids using the high-performance liquid chromatography with electrochemical detection (HPLC-ECD) and specific enzyme-linked immunosorbent assay, respectively. The norepinephrine (NE) levels in media from NP-treated female adrenal, except 100 pM NP, were significantly increased [control (CTL) vs 1 nM NP, p<0.001; vs 10 nM NP, p<0.05; vs 100 nM NP, p<0.001; vs 1 µM NP, p<0.01]. The NE secretion from male adrenal was higher when treated with 100 nM and 1 µM NP (CTL vs 100 nM NP, p<0.05; vs 1 µM NP, p<0.05, respectively). The aldosterone level in the female adrenal media treated with 100 pM NP was significantly decreased, on the other hand, that of media treated with 10 nM NP was significantly increased (CTL vs 100 pM NP, p<0.05; vs 10 nM NP, p<0.01). In male adrenal media, the aldosterone levels of 10 nM, 100 nM and 1 µM NP-treated media were significantly declined (CTL vs 10 nM NP, p<0.001; vs 100 nM NP, p<0.001; vs 1 µM NP, p<0.001). These results showed the NP treatment altered secretory pattern of aldosterone from adrenals of both sexes, showing sexual dimorphism. It may be helpful for understanding possible adrenal pathophysiology, and endocrine disrupting chemicals-related sexually dimorphic phenomena in adrenals.

Mechanisms of Lipopolysaccharide-induced Lipopolysaccharide Tolerance in the Expression of TNF-$\alpha$ and IL-8 in Peripheral Blood Monocytes (말초 혈액 단핵구의 TNF-$\alpha$와 IL-8 발현에서 내독소에 대한 내성 기전에 관한 연구)

  • Park, Gye-Young;Kim, Jae-Yeol;Yoo, Chul-Gyu;Kim, Young-Whan;Han, Sung-Koo;Shim, Young-Soo
    • Tuberculosis and Respiratory Diseases
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    • v.44 no.3
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    • pp.601-610
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    • 1997
  • Background : Monocytes/macrophages play a central role in determining the host response during Gram-negative infection through secretion of a variety of mediators after stimulation of LPS. Even though cytokine production has been shown to play an important role in host defense during sepsis, cytokine release may also lead to tissue injury. Thus, regulation of macrophage response to LPS is critical for host survival during Gram-negative sepsis. In animals exposed to nonlethal doses of endotoxin, a characteristic hyporesponsiveness to subsequent administration of endotoxin has been observed. This phenomenon was known as 'LPS tolerance'. However, little information is available regarding the underlying mechanism of LPS tolerance. Method : Peripheral blood monocyte(PBMC) was isolated from peripheral blood of normal volunteers by adhesion purification method. To evaluate the conditions to obtain LPS tolerance, preculture was carried out with LPS at 10ng/ml for 24 hours. For stimulation, culture plates were washed two times and were stimulated with LPS at $1{\mu}g/ml$ for 4, 6 and 26 hours. To assess the underlying mechanisms of LPS tolerance, autologous serum, PMA, anti-CD14 Ab, Indomethacin or $PGF_2$ were added to preculture solution respectively. Cytokine concentrations in culture supernatants were measured using ELISA for TNF-$\alpha$ and IL-8 and mRNA of TNF-$\alpha$ and IL-8 were determined by Northern blot analysis. Results : The exposure of PBMC to low dose of LPS suppressed the cytokine production and mRNA expression of TNF-$\alpha$, but not IL-8. Anti-CD14 Ab partially recovered production of TNF-$\alpha$ which was suppressed by preculture with low dose LPS. The preculture with PMA induces LPS tolerance, as preculture with low dose LPS. Conclusion : LPS tolerance to TNF-$\alpha$ is regulated pretranslationally and is influenced by protein kinase C pathway and CD14.

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A Comparison of the Adjustment Methods for Assessing Urinary Concentrations of Cadmium and Arsenic: Creatinine vs. Specific Gravity (요중 카드뮴과 비소의 보정방법 비교 : 요중 크레아티닌과 요비중)

  • Kim, Dong-Kyeong;Song, Ji-Won;Park, Jung-Duck;Choi, Byung-Sun
    • 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.

Mitogenic and Cytotoxic Effect of pure Fumonisin B$_1$, a carcinogen, in Sprague-Dawley Rats. (Fumonisin B$_1$의 SD흰쥐에 대한 세포분열과 세포독성작용)

  • Lim, Chae Woong;Has;Rim, Byung Moo
    • Environmental Mutagens and Carcinogens
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    • v.16 no.1
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    • pp.1-5
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    • 1996
  • Fumonisin B$_1$ is hepatotoxic in all species, but liver carcinogenic and nephrotoxic in rat. Our objective was to investigate the effects of multiple iv dose of FB$_1$. Male Sprague-Dawley rats were injected intravenously (iv) with FB$_1$ at 1 mg/kg singly (T1), or daily for 2 (T2) or 3 (T3). T1 rats did not show any cytotoxicity in both liver and kidney. However, the most dramatic change occurred in this group was mitotic figures in liver, which increased 5.5-fold to that of control. Hepatotoxic effects were shown in T3, based on histopathology and serum chemistry. A few scattered single cell deaths occurred primarily in the centrilobular area of the liver in T2. Similar but more lesions in liver and a small number of degenerating cells with hypereosinophilic cytoplasm in outer stripe of medulla of kideny were found in T3 rats. Serum chemical profiles included liver enzymes increased, in which cholesterol was very sensitive. This study suggests that multiple exposure of low dose FB$_1$ cause cytotoxic in the liver earlier time point than kideny. FB$_1$$ also stimulates mitosis in liver that may be associated with carcinogenesis.

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Characterization of Antioxident Enzymes in the Lung of Rat Exposed to Cigarette Smoke (흡연한 흰쥐 폐조직 항산화효소들의 특성)

  • 이영구;손형옥;임흥빈;이동욱;박준영
    • Journal of the Korean Society of Tobacco Science
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    • v.15 no.1
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    • pp.3-14
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    • 1993
  • Oxidants in environment or cigarette smoke are known to be implicated in the oxidative damages of pulmonary system. Such cellular damages are prevented by the presence of adequate levels of antioxidants in the tissue. In the present study, we investigated the influences of smoking duration and concentration of smoke on lung antioxidant defense in rats. Subchronic exposure of rats to smoke generated from 6 cigarettes per day for 90 days caused the activities of catalase and superoxide dismutase (SOD) to increase. However, glutathione peroxidase (GP-Xase) was not significantly changed. Total sulfhydryl compounds (Total-SH) in the lung homogenates from the rats inhaled with cigarette smoke for 15 days was decreased by 44% , thereafter it was returned to the level of normal rats. On the contrary, when rats were daily exposed to a different concentration of smoke generated from 1 to 20 cigarettes per day for 15 days, the activity of catalase was increased gradually with dose, but total SOD activity was increased only in the rats of low dose groups less than 5 cigarettes. Three types of SOD (one Cu, Zn-SOD with pI 4.9, and two Zn-SOD with pI 4.7 and 7.9)were detected in the lung homogenates and Zn-SOD with pI 4.7 was the major and cigarette-smoke inducible form. These results indicate that the protection of lung against oxidants from cigarette smoke seems to be accomplished by the induction of catalase and SOD, especially a cyanide resistant Zn-SOD with pI 4.f, following the consumption of antioxidants such as GSH in the beginning of inhalation period.

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Assessment of mulberry leaf as a potential feed supplement for animal feeding in P.R. China

  • Cai, Ming;Mu, Lan;Wang, Zong-li;Liu, Jian-yong;Liu, Tian-liang;Wanapat, Metha;Huang, Bi-zhi
    • Asian-Australasian Journal of Animal Sciences
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    • v.32 no.8
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    • pp.1145-1152
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    • 2019
  • Objective: Mulberry (Morus alba L.) is a cultivated shrub grown widely in the sub-tropical and tropical areas. It has been shown that mulberry leaf contains high levels of protein while having polyphenols as phytonutrients. Therefore, it is important to conduct an experiment to assess potential toxic level from mulberry on behavior, blood hematological and coagulation parameter using Sprague-Dawley (SD) rats. Methods: Both male and female SD rats were given an intragastric administration of respective treatments of mulberry leaf intakes (control, low and high levels). Parameters of feed intake, hematological and coagulation of blood parameters, as well as liveweight changes were taken during the 7 d of adaptation, 28 d of treatment exposure, and 14 d of recovery periods, respectively. All treatment data were statistically analyzed using analysis of variance of SPSS17.0 for Windows Statistical Software following the Randomized complete block design with sex as a block. Results: Most of the parameters of the physical symptoms of the SD rats, were not significantly different (p>0.05) when compared with that of the control group. Those which remain unchanged in each dose group were, body weight (BW) gain, feed intake, the hematology and coagulation indexes. Although, there were a few individual indicators that were abnormal, but the overall physiological appearance of the rats were normal. Conclusion: Results under this experiment revealed that most hematological and coagulation parameters of the SD rats in both male and female were normal, although the weight gain of female rats in high-dose group was significantly reduced than those of the male rats. Under this study, the use of mulberry leaf up to 2 g/kg BW did not result in abnormal phenomenon in the SD rats. These findings would offer useful information for further in vivo feeding trials in animals to extensively use of mulberry leaf to improve animal production, particularly in P.R. China.