• Title/Summary/Keyword: single dose oral toxicity

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Renal effect of experimental feeding of melamine and cyanuric acid in different concentrations on Japanese catfish (Silurus asotus) (멜라민과 cyanuric acid의 농도별 혼합투여에 따른 메기(Silurus asotus) 신장에서의 조직병리학적 소견)

  • Han, Se-Hee;Heo, Gang-Joon
    • Korean Journal of Veterinary Service
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    • v.34 no.1
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    • pp.75-79
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    • 2011
  • The recent outbreak of renal failure in infants in China and in animals in USA and Europe has been determined to be caused by melamine adulterated in the food. In the course of the investigation, cyanuric acid was identified in addition to melamine in the offending food. Fish feeds were also recently found to be contaminated with melamine. The purpose of this study was to characterize the histopathological effect and toxicity potential of different concentrations of melamine and cyanuric acid in the kidney of Japanese catfish (Silurus asotus). The fish were administered melamine and cyanuric acid in combination at the concentrations of 12.5, 25, 50, 100 and 200 mg/kg/day for 3 days by single oral administration dissolved in carboxymethyl cellulose. The results showed that renal crystals were observed in renal tubules and collecting ducts at the concentration over 25 mg/kg dose group and the number of crystals in kidney were in proportion to the concentrations of melamine and cyanuric acid.

Safety of Nano-sized Bee Pollen in both In-vitro and In-vivo Models (생체 외 및 생체 내 실험조건에서 나노화 벌 화분의 안전성 규명)

  • Pyeon, Hae-In;So, Soojeong;Bak, Jia;Lee, Seunghyun;Lee, Seungmin;Suh, Hwa-Jin;Lim, Je-Oh;Kim, Jung-Woo;Kim, Sun Youn;Lee, Se Ra;Lee, Yong Hyun;Chung, Il Kyung;Choi, Yun-Sik
    • Journal of Life Science
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    • v.28 no.5
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    • pp.605-614
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    • 2018
  • Bee pollen has an outer wall which is resistant to both acidic and basic solutions and even the digestive enzymes in the gastrointestinal tract. Therefore, the oral bioavailability of bee pollen is only 10-15%. A previous study reported on wet-grinding technology which increased the extraction of active ingredients from bee pollen by 11 times. This study was designed to investigate the safety of wet-ground bee pollen. First, a single dose of wet-ground bee pollen was tested in both rats and beagle dogs at dosages of 5, 10, and 20 g/kg and 1.5, 3, and 6 g/kg, respectively. In rats, compound-colored stools were found in those administered 10 g/kg or more of wet-ground bee pollen. In beagle dogs, 6 g/kg of wet-ground bee pollen induced diarrhea in one male for four hours. However, no obvious clinical signs were found through the end of the experiment in rats and beagle dogs. In addition, no histological abnormality was found in all animals. The data indicates that a single dose of up to 20 g/kg of wet-ground bee pollen is safe. Next, the genetic toxicity of nano-sized bee pollen was tested. This study employed a bacterial reverse mutation test, a micronucleus assay, and a chromosomal aberration assay. In the micronucleus assay, there was no genetic toxicity up to the dosage of 2 g/kg. There was also no genetic toxicity in the bacterial reverse mutation test and chromosomal aberration assay. This data provides important information in developing nano-sized bee pollen into more advanced functional foods and herbal medicines.

Role of Concomitant Chemoradiation in Locally Advanced Head and Neck Cancers

  • Lasrado, Savita;Moras, Kuldeep;Pinto, George Jawahar Oliver;Bhat, Mahesh;Hegde, Sanath;Sathian, Brijesh;Luis, Neil Aaron
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.10
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    • pp.4147-4152
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    • 2014
  • Standard therapy for advanced head and neck cancer consists of a combination of surgery and radiation. However, survival of this patient population has not improved during the past 20 years. Many different multimodality treatment schedules have been proposed, and chemotherapy is often used with the intent of organ preservation. The present study was intended to establish the efficacy of concomitant chemoradiation with a single agent carboplatin in advanced head and neck cancers.The objectives were to investigate the feasibility of concomitant administration of carboplatin, monitor acute toxicity during radiotherapy, and determine subacute side effects, such as wound healing following surgery after chemoradiotherapy. A prospective study was conducted wherein a total of 40 patients with stage III and IV squamous cell carcinomas of oral cavity, oropharynx, hypopharynx and larynx were enrolled. All patients were treated with external beam radiotherapy and weekly carboplatin area under curve (AUC of 5). Radiotherapy was given in single daily fractions of 1.8-2 grays (Gy) to a total dose of 66-72 Gy. Salvage surgery was performed for any residual or recurrent locoregional disease. Neck dissection was recommended for all patients with neck disease showing less than a complete response after chemoradiation. A total of 40 patients were enrolled of whom 32 were males and 8 were females. Highest incidence of cancer was seen in the 5th-6th decades of life with a median age of 47.7 years. Oropharyngeal tumours constituted a maximum of 21 patients followed by hypopharynx in 10, larynx in 7 and oral cavity in 2. 80% of the patients had a neck node on presentation of which 40% had N2-N3 nodal status. TNM staging revealed that 58% of patients were in stage III and 43% in stage IV. Evaluation of acute toxicity revealed that 50% had grade II mucositis, 25% grade III mucositis, 2.5% grade IV mucositis. 50% of patients had grade I skin reactions, 65% of patients had grade I thrombocytopenia, and 24% of patients had grade I anaemia. After completion of treatment 65% of patients had complete response at the primary and regional sites, and 35% of patients had a partial response of whom 23% underwent neck dissection and 5% of them underwent salvage surgery at the primary site. At the end of one year there were six deaths and four recurrences and 70% were free of disease. Concurrent chemoradiation with carboplatin provided good locoregional control for locally advanced head and neck cancers. This regimen, although toxic, is tolerable with appropriate supportive intervention. Primary site conservation is possible in many patients. Chemoradiotherapy appears to have an emerging role in the primary management of head and neck cancers.

Acute Toxicity of Leuconostoc Citreum GR1 Isolated from Kimchi in Mice (김치로부터 분리한 Leuconostoc citreum GR1의 마우스에 대한 급성독성)

  • Lee, Hwan;Cha, Seon-Suk;Lee, Myung-Yul;Chang, Hae-Choon;Lee, Jae-Joon
    • Food Science and Preservation
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    • v.20 no.1
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    • pp.121-126
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    • 2013
  • The present study was carried out to investigate the in vivo single-dose acute toxicity of Leuconostoc citreum GR1 (Leuc. citreum GR1), a lactic acid bacteria isolated from kimchi, in ICR male and female mice. The test article was orally administered once to both sexes of mice. The mortalities, clinical findings, autopsy findings, and body weight changes were monitored daily for two weeks. The male and female mice were gavaged with Leuc. kimchi GR1 of four doses (625, 1,250. 2,500 and 5,000 mg/kg). The oral $LD_{50}$ of Leuc. citreum GR1 was considered higher than 5,000 mg/kg. No significant changes in the general conditions, body weights, clinical signs and presence of gross lesions were observed in both sexes of mice to whom Leuc. citreum GR1 was administered orally. The results indicated that the 5,000 mg/kg dose of Leuc. citreum GR1 showed no adverse effect.

Weekly Cisplatin-Based Concurrent Chemoradiotherapy for Treatment of Locally Advanced Head and Neck Cancer: a Single Institution Study

  • Ghosh, Saptarshi;Rao, Pamidimukkala Brahmananda;Kumar, P Ravindra;Manam, Surendra
    • Asian Pacific Journal of Cancer Prevention
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    • v.16 no.16
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    • pp.7309-7313
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    • 2015
  • Background: The organ preservation approach of choice for the treatment of locally advanced head and neck cancers is concurrent chemoradiation with three weekly high doses of cisplatin. Although this is an efficacious treatment policy, it has high acute systemic and mucosal toxicities, which lead to frequent treatment breaks and increased overall treatment time. Hence, the current study was undertaken to evaluate the efficacy of concurrent chemoradiation using 40 mg/m2 weekly cisplatin. Materials and Methods: This is a single institutional retrospective study including the data of 266 locally advanced head and neck cancer patients who were treated with concurrent chemoradiation using 40 mg/m2 weekly cisplatin from January 2012 to January 2014. A p-value of < 0.05 was taken to be significant statistically for all purposes in the study. Results: The mean age of the study patients was 48.8 years. Some 36.1% of the patients had oral cavity primary tumors. The mean overall treatment time was 57.2 days. With a mean follow up of 15.2 months for all study patients and 17.5 months for survivors, 3 year local control, locoregional control and disease free survival were seen in 62.8%, 42.8% and 42.1% of the study patients. Primary tumor site, nodal stage of disease, AJCC stage of the disease and number of cycles of weekly cisplatin demonstrated statistically significant correlations with 3 year local control, locoregional control and disease free survival. Conclusions: Concurrent chemoradiotherapy with moderate dose weekly cisplatin is an efficacious treatment regime for locally advanced head and neck cancers with tolerable toxicity which can be used in developing countries with limited resources.

A Comparative Toxicological Study of Dried Mylabris phalerata Extract and it's Modifier : Single Dose Toxicity on Male Mice (반묘(斑猫)와 가공반묘(加工斑猫)의 단회투여(單回投與) 독성에 대한 비교연구)

  • Roh, Heui-Mok;Kim, Seong-Mo;Choi, Hong-Sik
    • The Korea Journal of Herbology
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    • v.24 no.3
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    • pp.1-12
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    • 2009
  • Objectives : The objective of this study was to compare, the potency of toxicity of Cantharidin containing dried Mylabis phalerata (MP) extract and it's modifier. Methods : They were monitored at dosage level 2,000, 1,000, 500, 250 and 125 mg/kg, respectively. Changes of body weight, clinical signs, mortality, LD50, macroscopic changes of gastrointestinal tract and liver were observed after single oral dose of test articles with changes of serum Gastrin and Somatostatin levels. Results : Dosage-dependent decrease of body weight and/or gains were demonstrated in dried MP extract-dosing groups, were also detected in modified and dried MP extract-dosing groups at 2,000 and 1,000 mg/kg-dosing group. However, below 500 mg/kg-dosing group, the body weights were significantly increased compared to that of equal dosage group of dried MP extract-dosing group. Dosage-dependently detected clinical signs in dried MP extract-dosing groups, were also detected in modified and dried MP extract-dosing groups at 2,000 and 1,000 mg/kg-dosing group. However, below 500 mg/kg-dosing group, these clinical signs dramatically were decreased compared to that of equal dosage group of dried MP extract-dosing group. Dosage-dependent increase of mortality rates were observed in dried MP extract-dosing groups, were also detected in modified and dried MP extract-dosing groups at 2,000 and 1,000 mg/kg-dosing group. However, below 500 mg/kg-dosing group, the mortalities were significantly decreased compared to that of equal dosage group of dried MP extract-dosing group. The LD50 of dried MP extract in male mice was dramaticlly increased in their modify, 265.86 vs 426.99 mg/kg. Dosage-dependently increase of number of hemorrhagic and/or erythematous spots detected in the gastrointestinal tracts of dried MP extract-dosing groups, were also detected in modified and dried MP extract-dosing groups at 2,000 and 1,000 mg/kg-dosing group. However, below 500 mg/kg-dosing group, these abnormal spots were dramatically decreased compared to that of equal dosage group of dried MP extract-dosing group. Dosage-dependently increase of degrees of enlargement and congestion detected in the liver of dried MP extract-dosing groups, were also detected in modified and dried MP extract-dosing groups at 2,000 and 1,000 mg/kg-dosing group. However, below 500 mg/kg-dosing group, these abnormal signs were dramatically decreased compared to that of equal dosage group of dried MP extract-dosing group. Dosage-dependently increase of serum gastrin levels of dried MP extract-dosing groups, were also detected in modified and dried MP extract-dosing groups at 2,000 and 1,000 mg/kg-dosing group. However, below 500 mg/kg-dosing group, these abnormal increase were dramatically decreased compared to that of equal dosage group of dried MP extract-dosing group. Dosage-dependently increase of serum somatostatin levels of dried MP extract-dosing groups, were also detected in modified and dried MP extract-dosing groups at 2,000 and 1,000 mg/kg-dosing group. However, below 500 mg/kg-dosing group, these abnormal increase were dramatically decreased compared to that of equal dosage group of dried MP extract-dosing group. Conclusions : The toxicity of dried MP extract was reduced by their modify.

The Literatual Study of Yijin-tang-gamibang Effects on Reflux Esophagitis (역류성 식도염에서의 이진탕가미방(二陳湯加味方)의 효과에 대한 문헌적 고찰)

  • Kim, Keun-Hong;Lee, Jong-Ho;Cho, Chong-Kwan;Yoo, Hwa-Seung;Lee, Yeon-Weol
    • Journal of Haehwa Medicine
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    • v.22 no.1
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    • pp.119-128
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    • 2013
  • Objectives: Yijin-tang-gamibang has been used in the Korean Medicine for treating various digestive disease. This study was aimed to investigate the effects and safety of Yijin-tang-gamibang in reflux esophagitis through the analysis of articles. Method: A total of 9 articles about Yijin-tang-gamibang and reflux esophagitis were used to develop this article. Results: According to basic research and clinic research data, it is supported that Yijin-tang-gamibang was useful prescription in reflux esophagitis. Yijin-tang-gamibang has favorable protective effects on the reflux esophagitis induced by pylorus and forestomach ligation in rats. After treatment with Yijin-tang-gamibang, patients showed improvement in all symptoms associated with reflux esophagitis and functional dyspepsia, including general condition. And Yijin-tang-gamibang did not show any toxic effect in single oral dose toxicity test. Conclusion: The results of this study suggest that Yijin-tang-gamibang showed favorable protective effects on the reflux esophagitis. However, it proved insufficient to confirm its efficacy owing to lack of clinical studies of high quality. So, we need well designed studies to verify clinical efficacy of Yijin-tang-gamibang hereafter.

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.

Effects of Recombinant Human Epidermal Growth Factor (rhEGF) on Experimental Radiation-Induced Oral Mucositis in Rats (Rat의 방사선 조사성 구내염에 대한 Recombinant Human Epidermal Growth Factor (rhEGF)의 효과)

  • Jung Kwon-Il;Kim Sun-Hee;Moon Soo-Young;Kim Yeon-Wha;Hong Joon-Pio;Kim Hyun-Sook;Lee Sang-Wook
    • Radiation Oncology Journal
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    • v.24 no.1
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    • pp.67-76
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    • 2006
  • Purpose: Oral mucositis is a common toxicity of radiation or chemotherapy, which is used a treatment for head and neck cancer. We investigated effects of recombinant human epidermal growth factor (rhEGF) on radiation-induced oral mucositis in rat model. Materials and Methods: Spraque-Dawley rats (7 per group) exposed to a single dose of 25 Gy (day 0) on their head, except for one group, were randomly divided into un-treated, vehicle-treated, and two rhEGF-treated groups. Rats were topically applied with rhEGF (15 or $30{\mu}g/oral$ cavity/day) or vehicle to their oral mucosa. Survival rate of rats, weight changes, and food intakes were examined from day 0 to 18 after radiation. Histology study was performed from oral mucosa of rats at day 7 and 18 after radiation. Results: rhEGF-treated groups (15 or $30{\mu}g/oral$) showed all survival rate 33%, whereas un-treated and vehicle-treated groups showed all survival rate 0% at the end of experiment. rhEGF-treated groups statistically had less weight loss compared to vehicle-treated group from day 2 to 7 after radiation. Food intake of rats with rhEGF treatment turned to increase at day 14 after radiation. At 7 day after radiation, un-treated and vehicle-treated groups showed severe pseudomembraneous or ulcerative oral mucositis. On the other hand, rhEGF-treated groups had no more than cellular swelling and degeneration of epidermal cells in oral mucosa of rats. Conclusion: These results suggest that rhEGF has significantly positive effects on radiation-induced oral mucositis in rats. rhEGF display a therapeutic potential on a clinical level.

Collection, Identification and Hepatic Effect of Native Cordyceps militaris (새로운 번데기 동충하초의 수집, 동정 및 간기능에 미치는 효과)

  • Lee, Ki-Won;Nam, Byung-Hyouk;Jo, Wool-Soon;Oh, Su-Jung;Kang, Eun-Young;Cui, Yong;Lee, Jae-Yun;Cheon, Sang-Cheol;Jeong, Min-Ho;Lee, Jae-Dong
    • The Korean Journal of Mycology
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    • v.34 no.1
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    • pp.7-14
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    • 2006
  • Entomopathogenic fungus Cordyceps militaris is famous for its medicinal efficacies. It has been reported to have various pharmacological activities such as anti-tumour, insecticidal, antibacterial, immunomodulatory and antioxidant. In this study, we investigated the effect of the extract of C. militaris (MPUN8501), which was identified by the analysis of the nucleotide sequences of 5.8S ribosomal RNA, on the function of liver. C. militaris powder was extracted using hot water extracts method as time, volume and temperature and using method as differential polarity of organic solvent. Each fraction was tested for the improvement of hepatic enzyme alcohol dehydrogenase (ADH) and acetaldehyde dehydrogenase (ALDH) activity. The BuOH extracts (CME) had highest activity which was used for the test of toxicity and efficacy of C. militaris. The enhancing effect of CME on the activity of ADH and ALDH was much more than medicine, drink, natural tea etc. Thus CME promoted the resolution of alcohol and acetaldehyde in rats, inducing recovery to normal condition rapidly. Furthermore, oral administration of CME effectively protected the carbon tetrachloride-induced acute hepatic injury as revealed by the hematological parameters (levels of sGOT and sGPT) and histological observation. CME was ascertained to be safe by regulatory toxicity studies of single dose toxicity and genotoxicity. These results suggest that CME would be useful for the maintaining normal hepatic activity as a functional health food.