• Title/Summary/Keyword: organ toxicity

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Induction of Metallothionein and Toxicity in Acute Cadmium Intoxicated Rat (카드뮴 급성폭로에 의한 Metallothionein 생성과 독성작용)

  • Min, Kyung-Joon;Park, Jung-Duck;Hong, Yeon-Pyo;Chang, Im-Won
    • Journal of Preventive Medicine and Public Health
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    • v.26 no.2 s.42
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    • pp.231-250
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    • 1993
  • Thirty five male Sprague-Dawley rats were treated with cadmium chloride solution ranging from 0.2 to 3.2mg $CdCl_2/kg$ by intravenous single injection. At 48 hours after administration of cadmium, total cadmium, MT bound cadmium and histopathologic finding in liver, kidney, lung, heart, testis, metallothionein in liver, kidney and total cadmium in bleed were examined. Tissue cadmium concentration was highest in liver, followed by in kidney, heart, lung and testis. Cadmium bound to rnetallothionein (MT-Cd) and ratio of MT-Cd to total cadmium were increased in liver and kidney dependently of cadmium exposure dose, but not significantly changed in other organs. On histopathologic finding, the most susceptible organ was heart in considering cadmium exposed dose, but testis in considering cadmium concentration. Blood cadmium concentration was increased with dose-dependent pattern, and significantly correlated with tissue cadmium concentration, so that we may estimate tissue cadmium concentration by measurement of blood cadmium concentration. Metallothionein in liver and kidney was increased with dose-dependent pattern, higher in liver than in kidney, and was significantly correlated with tissue cadmium concentration. However, metallothionein induction efficiency of tissue cadmium(${\mu}g\;MT/{\mu}g\;Cd$) was eater in liver than in kidney, and reverse to tissue concentration or exposed dose of cadmium.

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Freeze-Dried Powder of Rubus coreanus Miquel Ameliorates Isoproterenol-Induced Oxidative Stress and Tissue Damage in Rats

  • Kim, Jin Tae;Qiu, Shuai;Zhou, Yimeng;Moon, Ji Hyun;Lee, Seung Beom;Park, Ho Jin;Lee, Hong Jin
    • Journal of Microbiology and Biotechnology
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    • v.31 no.9
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    • pp.1256-1261
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    • 2021
  • Rubus coreanus Miquel (bokbunja), Korean black raspberry, is known to possess various phytochemicals that exert antioxidative, anti-inflammatory, and anti-cancer effects. However, most studies on Rubus coreanus Miquel have been performed with the solvent extracts and/or a single component to demonstrate the efficacy, while studies evaluating the effect of the whole fructus of Rubus coreanus Miquel are limited. In this study, therefore, we employed the isoproterenol (IPN)-induced myocardial infarction model and investigated the effect of freeze-dried powder of Rubus coreanus Miquel (RCP) on oxidative stress and prevention of organ damage. Oral administration of RCP reduced the level of toxicity markers, alanine transaminase (ALT), aspartate transaminase (AST), and lactate dehydrogenase (LDH) without affecting body weight and diet intake. The oxidative stress marker glutathione (GSH) increased about 45% and malonaldehyde (MDA) decreased about 27% compared to the IPN group with RCP-H (3%) administration. By histological analysis, IPN induced significant myocardial damage in the heart and vascular injury in the liver, and RCP administration ameliorated the damages in a dose-dependent manner. Taken together, RCP activated the antioxidant system leading to prevention of damage to organs by IPN in rats, making it possible to expect beneficial efficacies by consuming the whole fructus of Rubus coreanus Miquel.

Effect of Yeonsan Ogye bioactive peptides on anti-oxidant indexes in rats' liver

  • Kim, Hye Won;Shim, Jung Hun;Kim, Ki Nam
    • Journal of Nutrition and Health
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    • v.52 no.4
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    • pp.408-411
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    • 2019
  • Purpose: This study investigated the effect of bioactive Yeonsan Ogye peptides (YOPs) intake on changes in the hepatic anti-oxidant indexes in male rats. Methods: Sprague-Dawley male rats were divided into 3 groups and given a casein-based AIN-93G diet and distilled water ad libitum without any added YOPs (control), distilled water with 250 mg of YOPs (Y250), or 500 mg of YOPs (Y500) per kg of body weight for 4 weeks. YOP dose was decided as referred to in the referenced study where toxicity did not occur. The hepatic anti-oxidant indexes were determined using a commercial kit. Statistical analysis was performed using SPSS version 23.0 and are expressed as $mean{\pm}standard$ error of mean. Differences among the groups were evaluated by one-way analysis of variance followed by post hoc Duncan's multiple comparisons test. Results: There were no differences in the body weights, weight gain, food intake, food efficiency ratio, or organ weight, including liver, kidney, spleen, thymus, and epididymal fat, among all of the groups. The hepatic nitric oxide (NO) level in the Y500 group was lower than that in the control and Y250 groups, and the hepatic malondialdehyde (MDA) level was lower in the Y500 group than in the Y250 group. The differences in hepatic superoxide dismutase (SOD) and catalase (CAT) activities were not statistically significant between the groups. From these results we speculated that YOPs may have anti-oxidative abilities to regulate NO and MDA production without affecting SOD and CAT activities. Conclusion: YOPs are presumed to act as anti-oxidants in the animal or human body.

Feasibility Assessment of Physical Factors of Rectal Cancer Short-Course Chemoradiotherapy with Delayed Surgery

  • Koo, Jihye;Chung, Mijoo;Chung, Weon Kuu;Jin, Sunsik;Kim, Dong Wook
    • Progress in Medical Physics
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    • v.29 no.4
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    • pp.143-149
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    • 2018
  • To verify the correlations between the clinical outcomes and physical factors of short-course chemoradiotherapy (SCRT) and long-course chemoradiotherapy (LCRT) with delayed surgery in patients with rectal cancer. Seventy-two patients with rectal cancer were enrolled in this study. Nineteen patients were treated with SCRT (25 Gy, 5 fractions) by intensity-modulated radiation therapy (IMRT), and 53 patients were treated with LCRT (50.4 Gy, 28 fractions) by three-dimensional conformal radiation therapy (3DCRT). Various physical factors for the target and organs at risk (OARs) were calculated to compare the clinical outcomes. The organ equivalent dose (OED) and lifetime attributable risk (LAR) of bowels and bladders were similar between the SCRT and LCRT groups, whereas the values of femurs were higher in the LCRT group. The equivalent uniform dose and normal tissue complication probability were higher in the LCRT than the SCRT group for most organs. Treatment complications, including anastomotic leakage, bowel adhesion, and hematologic toxicity, were not significantly different between SCRT and LCRT groups. CIs were $0.84{\pm}0.2$ and $0.61{\pm}0.1$ for SCRT and LCRT, respectively. The CVIs were $1.07{\pm}0.0$ and $1.10{\pm}0.1$, and the HIs were $0.09{\pm}0.0$ and $0.11{\pm}0.1$ for SCRT and LCRT, respectively. The sphincter-saving rates were 89.5% and 94.3% for SCRT and LCRT, respectively. The complete pathologic remission rates were 21.1% and 13.2%, and the down-staging rates were 47.4% and 26.4% for SCRT and LCRT, respectively. SCRT with IMRT is comparable to conventional LCRT in both physical indexes and clinical outcome. The preoperative SCRT, compensated by IMRT, is an effective and safe modality.

The Effect of γ-Aminobutyric Acid Intake on UVB- Induced Skin Damage in Hairless Mice

  • Hairu Zhao;Bomi Park;Min-Jung Kim;Seok-Hyun Hwang;Tae-Jong Kim;Seung-Un Kim;Iksun Kwon;Jae Sung Hwang
    • Biomolecules & Therapeutics
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    • v.31 no.6
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    • pp.640-647
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    • 2023
  • The skin, the largest organ in the body, undergoes age-related changes influenced by both intrinsic and extrinsic factors. The primary external factor is photoaging which causes hyperpigmentation, uneven skin surface, deep wrinkles, and markedly enlarged capillaries. In the human dermis, it decreases fibroblast function, resulting in a lack of collagen structure and also decreases keratinocyte function, which compromises the strength of the protective barrier. In this study, we found that treatment with γ-aminobutyric acid (GABA) had no toxicity to skin fibroblasts and GABA enhanced their migration ability, which can accelerate skin wound healing. UVB radiation was found to significantly induce the production of matrix metalloproteinase 1 (MMP-1), but treatment with GABA resulted in the inhibition of MMP-1 production. We also investigated the enhancement of filaggrin and aquaporin 3 in keratinocytes after treatment with GABA, showing that GABA can effectively improve skin moisturization. In vivo experiments showed that oral administration of GABA significantly improved skin wrinkles and epidermal thickness. After the intake of GABA, there was a significant decrease observed in the increase of skin thickness measured by calipers and erythema. Additionally, the decrease in skin moisture and elasticity in hairless mice exposed to UVB radiation was also significantly restored. Overall, this study demonstrates the potential of GABA as functional food material for improving skin aging and moisturizing.

Aflatoxin B1-induced oxidative stress in canine small intestinal cells

  • Hyun-Woo Cho;Kangmin Seo;Min Young Lee;Sang-Yeob Lee;Kyoung Min So;Ki Hyun Kim;Ju Lan Chun
    • Journal of Animal Reproduction and Biotechnology
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    • v.39 no.2
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    • pp.105-113
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    • 2024
  • Background: Aflatoxin B1 (AFB1) is a toxic metabolite generated by Aspergillus species and is commonly detected during the processing and storage of food; it is considered a group I carcinogen. The hepatotoxic effects, diseases, and mechanisms induced by AFB1 owing to chronic or acute exposure are well documented; however, there is a lack of research on its effects on the intestine, which is a crucial organ in the digestive process. Dogs are often susceptible to chronic AFB1 exposure owing to lack of variation in their diet, unlike humans, thereby rendering them prone to its effects. Therefore, we investigated the effects of AFB1 on canine small intestinal epithelial primary cells (CSIc). Methods: We treated CSIc with various concentrations of AFB1 (0, 1.25, 2.5, 5, 10, 20, 40, and 80 μM) for 24 h and analyzed cell viability and transepithelial-transendothelial electrical resistance (TEER) value. Additionally, we analyzed the mRNA expression of tight junction-related genes (OCLN, CLDN3, TJP1, and MUC2), antioxidant-related genes (CAT and GPX1), and apoptosis-related genes (BCL2, Bax, and TP53). Results: We found a significant decrease in CSIc viability and TEER values after treatment with AFB1 at concentrations of 20 μM or higher. Quantitative polymerase chain reaction analysis indicated a downregulation of OCLN, CLDN3, and TJP1 in CSIc treated with 20 μM or higher concentrations of AFB1. Additionally, AFB1 treatment downregulated CAT, GPX1, and BCL2. Conclusions: Acute exposure of CSIc to AFB1 induces toxicity, and exposure to AFB1 above a certain threshold compromises the barrier integrity of CSIc.

Toxic Impact Analysis by Exposure Duration of Dog Studies for Pesticides using in Korea (국내 사용농약의 노출 기간이 개의 독성반응에 미치는 영향 분석)

  • Lee, Je Bong;Jeong, Mi-Hye;You, Are-Sun;Hong, Soonsung;Paik, Min-Kyoung;Oh, Jin-Ah;Park, Kyung Hun;Ihm, Yang Bin
    • The Korean Journal of Pesticide Science
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    • v.17 no.4
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    • pp.350-358
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    • 2013
  • Both 13-week and 1-year studies in dog were required for pesticide registration in domestic pesticide control authority. It is raising issue up whether to request 1-year dog study of pesticides using non-food crop. So at this investigation, relevant toxicity test to establish acceptable daily intake (ADI), target organs, difference of no-observed adverse-effect levels (NOAELs) in 13-week and 1-year of 166 active ingredients are analyzed. The data were evaluated to determine if the 13-week dog study and the long term studies in two rodent species (mice and rats) without 1-year dog study were sufficient for the identification of NOAELs and lowest observed adverse effect levels (LOAELs) for the derivation of ADI. Toxicity end points and dose response data from 13 week and 1-year studies were compared. The analysis showed that 68 ADIs of the 166 pesticides were established from dog studies. Major target organs of dog studies were liver in 49 cases, body weight change in 21 cases, cholinesterase inhibition in 16 cases, and alteration in hematology in 14 cases. Similarity of target organ in 13-week and 1-year was 73%. 22 of 40 pesticides had similar critical effects regardless of duration and had NOAELs within a difference of 1.5-fold of each other. For the remaining 18 pesticides, 14 items had lower NOAELs in the 1-year study than 13-week study primarily due to dose selection and spacing. In only 10% of the cases were additional toxic effects identified in the 1-year study that were not observed in the 13-week study.

Effects of Aqueous Azadirachta indica Extract on Hepatotoxicity in Rats (수용성 님추출물이 랫드의 간 독성에 미치는 영향)

  • Park, Kyung-Hun;Yoon, Hyunjoo;Han, Beom Seok;Lee, Je-Bong;Jeong, Mi Hye;Cho, Namjun;Om, Ae Son;Paik, Min-Kyoung
    • Korean Journal of Environmental Agriculture
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    • v.33 no.4
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    • pp.395-402
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    • 2014
  • BACKGROUND: Azadirachta indica Extract(AIE) containing azadirachtin as active ingredient have been used worldwide as environment-friendly organic material having pest control properties. However, the extracts prepared with different solvent and from different plant site is very diverse and have different toxicity. METHODS AND RESULTS: In this study, the four week repeated oral dose toxicity test of aqueous AIE in Sprague-Dawley rats was carried out to investigate the toxic effect of liver, main toxicity target organ of AIE. The male and female rats were divided into 4 groups, respectively; control(0 g/Kg bw), low-dose group(0.5 g/Kg bw), middle-dose(1.0 g/Kg bw) and high-dose group(2.0 g/Kg bw). As a results, relative liver weight increased with dose-dependent of AIE(p<0.05). Serum LDH in all AIE-treated groups were significantly lower than the control in male rats(p<0.05). However, serum GOT and GPT were significantly increased in all male AIE-treated groups in male rats(p<0.05) and, in particular, increase of serum GPT in dose-dependent manner raise the possibility of liver damage. Even through serum GLU was increased significantly in high-dose group in male rats compared to control, there were no significant differences of urinary GLU among all groups(p<0.05). In addition, histopathological examination of the liver did not reveal any lesions in all AIE-treated groups. CONCLUSION: In conclusion, 4 weeks of the repeated oral administration of AIE 2.0 g/Kg to rats has resulted no toxic response in liver. Therefore, AIE was no indicated to have any toxic effect in the SD rats, when it was orally administrated below the dosage 2.0 g/Kg/day for 4weeks.

Early Pulmonary Irradiation in Paraquat ($Gramoxone^{(R)}$) Poisoning (Paraquat 중독 환자에서 전폐 방사선치료의 효과)

  • Lee, Chang-Geol;Kim, Gwi-Eon;Suh, Chang-Ok
    • Radiation Oncology Journal
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    • v.13 no.4
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    • pp.321-330
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    • 1995
  • Purpose : To evaluate whether the early pulmonary irradiation can prevent or decrease the pulmonary damage and contribute to improve ultimate survival in paraquat lung. Materials and Methods : From Jun. 1987 to Aug. 1993, thirty patients with paraquat poisoning were evaluated. Fourteen of these patients were received pulmonary irradiation(RT). All of the patients were managed with aggressive supportive treatment such as gastric lavage, forced diuresis, antioxidant agents and antifibrosis agents. Ingested amounts of paraquat were estimated into three groups(A : minimal 50cc). Pulmonary irradiation was started within 24 hours after admission(from day 1 to day 11 after ingestion of paraquat). Both whole lungs were irradiated with AP/PA parallel opposing fields using Co-60 teletherapy machine. A total of 10Gy(2Gy/fr. x 5days) was delivered without correction of lung density. Results : In group A, all patients were alive regardless of pulmonary irradiation and in group C, all of the patients were died due to multi-organ failure, especially pulmonary fibrosis regardless of pulmonary irradiation. However, in group B, six of 7 patients($86{\%}$) with no RT were died due to respiratory failure, but 4 of 8 patients with RT were alive and 4 of 5 patients who were received pulmonary irradiation within 4 days after ingestion of paraquat were all alive though radiological pulmonary change. One patient who refused RT after 2Gy died due to pulmonary fibrosis. All 3 patients who were received pulmonary irradiation after 4 days after ingestion were died due to pulmonary fibrosis in spite of recovery from renal and hepatic toxicity Conclusion : It is difficult to find out the effect of pulmonary irradiation on the course of the paraquat lung because the precise plasma and urine paraquat concentration were not available between control and irradiation groups. But early pulmonary irradiation within 4 days after paraquat poisoning with aggresive supportive treatment appears to decrease Pulmonary toxicity and contribute survival in patients with mouthful ingestion of paraquat who are destined to have reversible renal and hepatic damage but irreversible pulmonary toxicity.

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A Study of the Additional Toxicity of Mixed Food Additives to Rat (혼합(混合)된 식품첨가물(食品添加物)이 흰쥐의 생리(生理)에 미치는 상승적(相乘的) 독성(毒性) 효과(效果)에 관(關)한 연구(硏究))

  • Chung, Ho-Kwon
    • Applied Biological Chemistry
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    • v.18 no.2
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    • pp.71-97
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    • 1975
  • To improve the food qualities in Korea, two hundred and fourtynine kinds of food additives have been allowed in food processing, of which one hundred and nineteen kinds could be used under the limitted conditions. Hence, in practical uses in food processing, many kinds of them are mixed at random within the permitted amounts for their special purposes. For last several years, many kinds of the food additives were prohibited because they have been proved to be toxic even with the single dose. Until recently a few studies on the toxicity in the mixture of food additives were reported, however, they were shown to be no severe additional effect on the animal. This study was performed to see if any elevation of chronic or subacute toxicity of food additives occur especially when they are mixed with each other, using three kinds of food additives (DHA, AF-2, BHT) most widely used as food preservatives, antiseptics and antioxidants. One hundred and fifty young male rats were taken and divided into ten feeding groups, one first control group (food additives blank), three second control groups (DHA 0.1%, AF-2 0.1%, BHT 0.5%), three mixture groups of low level (mixture of each 60% of two second control level) and three mixture groups of high level (mixture of each 90% of two second control level). As the methods of biological and clinical tests, the change of body weight (growth rate), daily intake of diets, organ to body weight ratio, histopathological findings of organs, hematological observation, liver and kidney function tests were checked three times during the periods of 24 weeks. The following results were obtained. 1. The low level group of DHA, AF-2 mixture and DHA, BHT mixture revealed a little retardation in growth rate than the first control group, however, they were similar to the second controls, while all the mixture groups of high level showed a more remarkable retardation than the first and second controls. 2. Average daily intake of the diets was the same in each group, showing a similar decreasing tendency (70-100g/kg of body weight) in accordance with the growth rate. It was observed that there are no differences in the taste and appetite in each group of rats. 3. Abnormal enlargements of kidney and lung were not seen in all the mixture groups compared with the controls, while a slight hepatomegaly was observed in all mixture groups of low level as in the second controls. Significant differences (almost 1% level) were observed between the high level groups and the first control group. 4. Histopathological effects of the food additives on lung, kidney and liver tissues were found in all mixture group of high level. The less frequencies of the same effects were also seen in the low level groups. 5. The esterified cholesterol to total cholesterol ratio in the mixture groups of high level showed a little lower values, and the activities of serum glutamate oxaloacetate transaminase and alkaline phosphatase decreased almost with significance of 5% level compared with the first control group. The serum A/G ratio in the mixture groups also decreased. The results demonstrated that the liver function was decreased in the mixture groups compared with the controls. 6. In all groups throughout the test period, kidney functions (concentration of protein and creatinine excreated per hour in urine and renal filtration rate) were shown almost as normal as the first control. 7. Average values of hematocrit, erythrocytes and leucocytes in the mixture groups were in the normal ranges as in the controls, which denotes that the production of blood cells in bone marrow were also normal in all groups. With the above results, it is concluded that when the food additives (DHA, AF-2, BHT) were given together to the rats in several combinations even in less amount, they showed more toxic signs than the single doses.

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