• Title/Summary/Keyword: Drug toxicity

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Concise Clinical Review of Hematologic Toxicity of Linezolid in Multidrug-Resistant and Extensively Drug-Resistant Tuberculosis: Role of Mitochondria

  • Oehadian, Amaylia;Santoso, Prayudi;Menzies, Dick;Ruslami, Rovina
    • Tuberculosis and Respiratory Diseases
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    • v.85 no.2
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    • pp.111-121
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    • 2022
  • Multidrug-resistant tuberculosis (MDR-TB) is caused by an organism that is resistant to both rifampicin and isoniazid. Extensively drug-resistant TB, a rare type of MDR-TB, is caused by an organism that is resistant to quinolone and one of group A TB drugs (i.e., linezolid and bedaquiline). In 2018, the World Health Organization revised the groupings of TB medicines and reclassified linezolid as a group A drug for the treatment of MDR-TB. Linezolid is a synthetic antimicrobial agent in the oxazolidinone class. Although linezolid has a good efficacy, it can cause substantial adverse events, especially hematologic toxicity. In both TB infection and linezolid mechanism of action, mitochondrial dysfunction plays an important role. In this concise review, characteristics of linezolid as an anti-TB drug are summarized, including its efficacy, pathogenesis of hematologic toxicity highlighting mitochondrial dysfunction, and the monitoring and management of hematologic toxicity.

A Study on the Acute Toxicity of Palmultang and Fermented Palmultang Extract in ICR Mice (ICR 마우스를 이용한 팔물탕 및 발효팔물탕의 급성독성 연구)

  • Jung, Kiyoun;Hwang, Youn-Hwan;Jang, Doorye;Ha, Jeong-Ho;Ma, Jin Yeul
    • Journal of Society of Preventive Korean Medicine
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    • v.17 no.1
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    • pp.117-124
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    • 2013
  • Objectives : This study was carried out to investigate the acute toxicity and safety of Palmultang and Fermented Palmultang Extract in Mice. Methods : To evaluate their acute toxicity and safety, 0 (control group), 2000 mg/kg of Palmultang and Fermented Palmultang Extracts were orally administered to 15 male and 15 female ICR mice. After a single administration, we observed survival rates, behavioral pattern, clinical sign, body weight. The results of biochemical analysis and hematological analysis were no any significant change. Results : Compared with the control group, we could not find any toxic alteration in all treated mice. Conclusions : Overall, the results suggest that, the oral administration of Palmultang and Fermented Palmultang extracts did not produce significant toxic effect in mice. Hence, the fermented extract can be utilized for herbal therapy.

Toxicity of a combination of florfrenicol and acetaminophen in pigs administered at overdose

  • Chae, Won-Seok;Yoo, Chang-Yeul;Tutkun, Lutfiye;Kim, Suk;Lee, Hu-Jang
    • Journal of Preventive Veterinary Medicine
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    • v.42 no.4
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    • pp.182-185
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    • 2018
  • This study examined the overdose toxicity of Super-Neophensan, containing florfenicol and acetaminophen, upon pigs. SNP-3.0 (n=10) was administered at the dosage level of 3 kg/ton feed for 7 consecutive days, which is 3 times the recommended dose based on the guidelines of the manufacturer, and the control group (CON) (n=10) was administered the normal diet without the drug. The body weight, weight gain and feed efficiency in SNP-3.0 treated with the drug for 14 days post-administration showed no significant differences compared with those in CON. In hematological and blood biochemical analyses, all parameters were not affected by over-dosage of the drug. In the same way, there were no significant differences between SNP-3.0 and CON on markers for liver and kidney functions. As no adverse effects were observed with the drug in an overdose oral toxicity test, this study suggests that the drug was identified as a safe agent in pigs administered with three times the recommended dose.

Analysis of the Growth Characteristics of Cardiac Cells According to Mechanical Properties of Substrates Using the Simplified Measurement Technique of Tracker

  • Abdullah, Abdullah;Kanade, Pooja P.;Oyunbaatar, Nomin-Erdene;Jeong, Yun-Jin;Kim, Dong-Su;Lee, Dong-Weon
    • Journal of Sensor Science and Technology
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    • v.31 no.1
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    • pp.6-11
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    • 2022
  • To date, various techniques have been utilized to assess the contractility of cardiomyocytes and their response to drug-induced toxicity. However, these techniques are either invasive or involve complex fabrication methods and expertise. Here, we introduce the use of video-based analysis software to track the motion of cardiomyocytes and assess their contractility. The software, called "Tracker", is freely available and this is the first attempt at using it for cardiac contractility measurement. We used the software to measure the contractile properties of cells cultured on a rigid substrate and two flexible polydimethylsiloxane (PDMS) substrates having different elastic moduli day-wise up to eight days. Contractility was found to be highest in the most flexible substrate. Subsequently, the cardiotoxicity response of the cells on three different substrates was analyzed with verapamil. It was observed that the cells on rigid substrate were primarily affected by drug-induced toxicity, while the drug had a lesser impact on cells on the more flexible PDMS substrate. Evidently, the flexible substrate aided the maturation of cells and had lower drug toxicity, while the cells on PS could not fully mature. The assessment of cardiomyocytes using "Tracker" proved to be simple and reliable.

Two-Week Repeated Dose Toxicity of Atractylodis Rhizoma Alba in F344 Rats

  • Han, Hyoung-Yun;Yang, Young-Su;Kim, Soo Nam;Han, Su-Cheol;Lee, Jong-Hwa;Jeong, Ja Young;Roh, Hang-sik;Seok, Ji Hyeon;Lee, Joo Sang;Kim, Jeong-Ah;Min, Byung-Sun
    • Natural Product Sciences
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    • v.22 no.3
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    • pp.180-186
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    • 2016
  • This research is to estimate the toxicity of Atractylodis Rhizoma Alba (ARA) in F344 rats and to find a dose level for the 13 weeks toxicity study. A hot water extract of ARA (ARWE) was administered orally to F344 rats at dose levels of 0 (vehicle control), 500, 1000, 2000, 3500, and 5000 mg/kg/day for 2 weeks. Each group was composed to five male and five female F344 rats. According to the result, there were no ARWE-related adverse changes in mortality, body weights, food consumption, urinalysis, hematology, clinical chemistry, gross finding at necropsy, and organ weight examination. Salivation was observed in 3500 and 5000 mg/kg/day in male and female rats but it could not have found any relationship with ARWE administration. Based on our findings, ARWE may not cause toxicity in rats under the experimental conditions. Therefore, dose level of 5000 mg/kg/day as a highest treatment group in 13-week exposure study is recommended for further toxicity assessment.

Principles and Methods for the Reproductive-toxicological Evaluation of New Drug Candidates (의약후보물질의 생식독성평가 원칙 및 방법)

  • 정문구;김종춘
    • Toxicological Research
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    • v.16 no.3
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    • pp.229-238
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    • 2000
  • The purpose of reproductive toxicity studies is to evaluate all effects resulting from paternal or maternal exposure that interfere with conception, development, birth, and maturation of offspring. In 1966, the US Food and Drug Administration (US FDA) published guidelines for a three-segment study for drug testing to examine adverse effects on fertility and pregnancy. Three segments were proposed: Segment I, Study of Fertility and General Reproductive Performance, to provide information on breeding, fertility, nidation, parturition, neonatal effects and lactation: Segment II, Teratological study, to provide information on embryo toxicity and teratogenicity: and Segment III. perinatal and Postnatal Study, to provide information on late fetal development, labour and delivery, neonatal viability, and growth and lactation. The classic guideline is still used to this day with only monor modification throughout the world. In the present review, the principles and methods of reproductive toxicity studies are discussed with special attention given to scientific issues.

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Toxicogenomics and Cell-based Assays for Toxicology

  • Tong, Weida;Fang, Hong;Mendrick, Donna
    • Interdisciplinary Bio Central
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    • v.1 no.3
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    • pp.10.1-10.5
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    • 2009
  • Toxicity is usually investigated using a set of standardized animal-based studies which, unfortunately, fail to detect all compounds that induce human adverse events and do not provide detailed mechanistic information of observed toxicity. As an alternative to conventional toxicology, toxicogenomics takes advantage of currently advanced technologies in genomics, proteomics, metabolomics, and bioinformatics to gain a molecular level understanding of toxicity and to enhance the predictive power of toxicity testing in drug development and risk/safety assessment. In addition, there has been a renewed interest, particularly in various government agencies, to prioritize and/or supplement animal testing with a battery of mechanistically informative in vitro assays. This article provides a brief summary of the issues, challenges and lessons learned in these fields and discuss the ways forward to further advance toxicology using these technologies.

A Study on the Acute Toxicity of Leejung-tang(Lizhong-tang) and Fermented Leejung-tang(Lizhong-tang) Extract in ICR Mice (ICR 마우스를 이용한 이중탕 및 발효이중탕의 급성독성 연구)

  • Jung, Young-Pil;Hwang, Yun-Hwan;Lee, Ji-Hye;Yim, Nam-Hui;Cho, Won-Kyung;Ma, Jin-Yeul
    • The Korea Journal of Herbology
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    • v.27 no.3
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    • pp.95-100
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    • 2012
  • Objectives : This study was carried out to investigate the acute toxicity and safety of $Leejung$-$tang$($Lizhong$-$tang$) and fermented $Leejung$-$tang$($Lizhong$-$tang$) extract. Methods : To evaluate their acute toxicity and safety, 0(control group), 1250, 2500 and 5000 mg/kg of $Leejung$-$tang$($Lizhong$-$tang$) and fermented $Leejung$-$tang$($Lizhong$-$tang$) extracts were orally administered to 35 male and 35 female ICR mice. After a single administration, we observed survival rates, general toxicity, changes of body weight, and autopsy. Results : Compared with the control group, we could not find any toxic alteration in any of treated groups (1250, 2500 and 5000 mg/kg). Conclusions : $LD_{50}$ of $Leejung$-$tang$($Lizhong$-$tang$) and fermented $Leejung$-$tang$($Lizhong$-$tang$) were over 5000 mg/kg and it is very safe to ICR mice.

Acute Toxicity Study on Gumiganghwal-tang and Fermented Gumiganghwal-tang Extracts (구미강활탕 및 발효 구미강활탕 추출물의 급성독성 연구)

  • Park, Hwayong;Hwang, Youn-Hwan;Jang, Doorye;Ha, Jeong-Ho;Jung, Kiyoun;Ma, Jin Yeul
    • Herbal Formula Science
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    • v.20 no.2
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    • pp.93-102
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    • 2012
  • Objectives : Traditional medicine Gumiganghwal-tang (GT) has been used in Asia to treat inflammatory diseases including common cold, pain, fever, and algor. In this study we investigated the acute toxicity and safety of GT and fermented GT (FGT). Methods : Acute toxicity and safety were evaluated in male and female ICR mice orally administered 0 (control) and 2,000 mg/kg of GT and FGT. After the administration of GT and FGT, we observed mortality, body weight, clinical symptoms. After necropsy, organ weights were measured and blood analysis was performed. Results : There was no mortality and clinical symptoms according to the administration of GT and FGT. Comparing with control group, there were no significant alterations on the organ weight, complete blood cell count and biochemical parameters. Conclusions : Median lethal dose of GT and FGT considered to be over 2,000 mg/kg in both male and female mice, and recognized as safe with no toxicity.