• Title/Summary/Keyword: Drug Toxicity

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Toxicity Assessment of Phytolaccae Radix Aqueous Extract Orally Administered to F344 Rats for Two Consecutive Weeks (상륙 추출물의 F344 랫드에서 2주 반복 경구투여 독성평가)

  • Han, Hyoung-Yun;Kang, Myung-Gyun;Yoon, Seokjoo;Seok, Ji-Hyeon;Kim, Jeong Ah;Kim, Tae-Won;Min, Byung Sun
    • Korean Journal of Pharmacognosy
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    • v.49 no.2
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    • pp.124-131
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    • 2018
  • Phytolaccae Radix has long been used as a traditional indigenous medicine to cure edema and rheumatism. However, there is insufficient background information on toxicological evaluation of Phytolaccae Radix extract to support the safe use. Therefore, we conducted a series of standardized, OECD and KFDA guidelines compliant in vivo study, to find a dose levels for the 13 weeks toxicity study. The extract of Phytolaccae Radix was administered orally to F344 rats at dose levels of 0, 500, 1000 and 2000 mg/kg/day for 2 weeks. Each group was composed to five male and five female rats. In the result, there were no test article-related adverse changes in clinical signs, body weight, food consumption, ophthalmology, hematology, clinical chemistry, gross finding at necropsy and organ weight examination. Therefore, we recommend that 2000 mg/kg/day is a highest treatment group in 13-week exposure study.

Albendazole and Mebendazole as Anti-Parasitic and Anti-Cancer Agents: an Update

  • Chai, Jong-Yil;Jung, Bong-Kwang;Hong, Sung-Jong
    • Parasites, Hosts and Diseases
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    • v.59 no.3
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    • pp.189-225
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    • 2021
  • The use of albendazole and mebendazole, i.e., benzimidazole broad-spectrum anthelmintics, in treatment of parasitic infections, as well as cancers, is briefly reviewed. These drugs are known to block the microtubule systems of parasites and mammalian cells leading to inhibition of glucose uptake and transport and finally cell death. Eventually they exhibit ovicidal, larvicidal, and vermicidal effects on parasites, and tumoricidal effects on hosts. Albendazole and mebendazole are most frequently prescribed for treatment of intestinal nematode infections (ascariasis, hookworm infections, trichuriasis, strongyloidiasis, and enterobiasis) and can also be used for intestinal tapeworm infections (taeniases and hymenolepiasis). However, these drugs also exhibit considerable therapeutic effects against tissue nematode/cestode infections (visceral, ocular, neural, and cutaneous larva migrans, anisakiasis, trichinosis, hepatic and intestinal capillariasis, angiostrongyliasis, gnathostomiasis, gongylonemiasis, thelaziasis, dracunculiasis, cerebral and subcutaneous cysticercosis, and echinococcosis). Albendazole is also used for treatment of filarial infections (lymphatic filariasis, onchocerciasis, loiasis, mansonellosis, and dirofilariasis) alone or in combination with other drugs, such as ivermectin or diethylcarbamazine. Albendazole was tried even for treatment of trematode (fascioliasis, clonorchiasis, opisthorchiasis, and intestinal fluke infections) and protozoan infections (giardiasis, vaginal trichomoniasis, cryptosporidiosis, and microsporidiosis). These drugs are generally safe with few side effects; however, when they are used for prolonged time (>14-28 days) or even only 1 time, liver toxicity and other side reactions may occur. In hookworms, Trichuris trichiura, possibly Ascaris lumbricoides, Wuchereria bancrofti, and Giardia sp., there are emerging issues of drug resistance. It is of particular note that albendazole and mebendazole have been repositioned as promising anti-cancer drugs. These drugs have been shown to be active in vitro and in vivo (animals) against liver, lung, ovary, prostate, colorectal, breast, head and neck cancers, and melanoma. Two clinical reports for albendazole and 2 case reports for mebendazole have revealed promising effects of these drugs in human patients having variable types of cancers. However, because of the toxicity of albendazole, for example, neutropenia due to myelosuppression, if high doses are used for a prolonged time, mebendazole is currently more popularly used than albendazole in anti-cancer clinical trials.

FA/Mel@ZnO nanoparticles as drug self-delivery systems for RPE protection against oxidative stress

  • Yi, Caixia;Yu, Zhihai;Sun, Xin;Zheng, Xi;Yang, Shuangya;Liu, Hengchuan;Song, Yi;Huang, Xiao
    • Advances in nano research
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    • v.13 no.1
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    • pp.87-96
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    • 2022
  • Drug self-delivery systems can easily realize combination drug therapy and avoid carrier-induced toxicity and immunogenicity because they do not need non-therapeutic carrier materials. So, designing appropriate drug self-delivery systems for specific diseases can settle most of the problems existing in traditional drug delivery systems. Retinal pigment epithelium is very important for the homeostasis of retina. However, it is vulnerable to oxidative damage and difficult to repair. Worse still, the antioxidants can hardly reach the retina by non-invasive administration routes due to the ocular barriers. Herein, the targeted group (folic acid) and antioxidant (melatonin) have been grafted on the surface of ZnO quantum dots to fabricate a new kind of drug self-delivery systems as a protectant via eyedrops. In this study, the negative nanoparticles with size ranging in 4~6 nm were successfully synthesized. They could easily and precisely deliver drugs to retinal pigment epithelium via eyedrops. And they realized acid degradation to controlled release of melatonin and zinc in retinal pigment epithelium cells. Consequently, the structure of retinal pigment epithelium cells were stabilized according to the expression of ZO-1 and β-catenin. Moreover, the antioxidant capacity of retinal pigment epithelium were enhanced both in health mice and photic injury mice. Therefore, such new drug self-delivery systems have great potential both in prevention and treatment of oxidative damage induced retinal diseases.

The oral dose toxicity test and skin irritation test of eco-friendly plasticizer using crude glycerol derived (폐글리세롤을 이용한 친환경 가소제의 경구투여독성 및 피부자극성 시험)

  • Kang, Soo-Jung;Kim, Heeyoung;Park, Sangwon;Sim, Eunyoung;Kim, Jinhwan
    • Journal of Korean Society of Occupational and Environmental Hygiene
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    • v.25 no.3
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    • pp.322-327
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    • 2015
  • Objectives: The major objective of this study is the oral dose toxicity test and skin irritation test of eco-friendly plasticizer using crude glycerol derived from the biodiesel process. Methods: Glyceroldiacetate laurate(GDL) was synthesized from glycerol monolaurat(GML) and acetic acid. The synthesis of the GDL plasticizer was measured with nuclear magnetic resonance spectroscop(NMR) and FT-IR(Fourier Transform Infrared Spectrometer). To provide information on the safety of GDL, we carried out an oral dose toxicity test for GDL in Sprague-Dawley rats. Also, we carried out a skin irritation test for GDL in New Zealand White rabbits. Results: The oral dose toxicity test in Sprague-Dawley rats showed that GDL is a non-toxic material. The result of the skin irritation test on New Zealand White rabbits showed that GDL is non-irritating. Conclusions: From the results of oral dose toxicity test and skin irritation test, we concluded that the developed plasticizer showed excellent eco-friendly property. Based on our results, we confirmed the development of an eco-friendly non-phthalate plasticizer. Applicability for PVC toys and food and drug packaging materials was found.

Single Dose Oral Toxicity Test of Peucedani Radix in ICR Mice (ICR 마우스를 이용한 전호의 단회경구투여 독성 실험)

  • Kwon, Da-hye;Kim, Min-young;Hwangbo, Hyun;Ji, Seon-yeong;Park, Cheol;Choi, Yung-hyun;Hong, Su-hyun
    • The Journal of Internal Korean Medicine
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    • v.39 no.4
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    • pp.676-685
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    • 2018
  • Objectives: The aim of this study was to estimate the single oral toxicity of Peucedani Radix (PR) ethanol extracts. PR is one of the important herbs for removal of phlegm, the viscous turbid pathological product that can accumulate in the body and cause a variety of diseases. However, research on the pharmacologic toxicity of PR is lacking. Methods: In this study, PR was orally administered to 5-week-old male ICR mice at an oral dose of 2,000, 3,000, or 5,000 mg/kg. After a single-dose administration, the mortality and behavioral changes were observed daily and body weights were measured every two days. After 14 days, the organ weight, organ index, macroscopy, hematological analysis, and serum biochemistry analysis were determined. Results: No mortality, body weight changes, abnormal behavioral changes, or anatomical signs of toxicity were found. The organ weight, organ index, hematological analysis, and serum biochemistry analysis were also within the normal ranges. Conclusions: These results suggest that the 50% lethal dose of PR is more than 5,000 mg/kg. This could indicate that PR is a safe drug without acute toxicity and side effects.

Single-and Repeated-Dose Toxicities of Compound K (CK) in Rats (랫드에서 Compound K (CK)의 단회 및 반복투여독성 평가)

  • Byeon, Jong Shin;Park, Ji Hyeon;Choi, Soon Jin;Ji, Yu Guen;Choi, Hak Joo;Kim, Dong Hee;Hwang, Seock Yeon
    • Journal of Haehwa Medicine
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    • v.22 no.1
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    • pp.171-184
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    • 2013
  • Single-and repeated-dose toxicities of Compound K (CK) were evaluated according to Toxicity Test Guidelines of Korea Food and Drug Administration using Sprague-Dawley rats. For single-dose toxicity study, CK was dissolved in drinking water, orally administered and examined for 14 days. As results, CK up to a dose of 5,000 mg/kg, the limited dose, neither induced death, clinical signs and necropsy findings, nor affected body weight gain and organ weights, in which 10% lethal dose could not be estimated. Based on the results of single-dose toxicity test, CK was administered at doses of 500, 1,000 or 2,000 mg/kg for 28 days for the evaluation of repeated-dose toxicity. All doses including the limited dose (2,000 mg/kg) of CK did not cause any abnormalities of rats, including mortality, clinical signs, body weight gain, feed/water consumption, necropsy findings, organ weights, hematology, blood biochemistry. Rather, high doses (1,000 - 2,000 mg/kg) of CK reduced the serum levels of alanine transaminase (ALT), aspartate transaminase (AST), creatinine phosphokinase (CPK), lactate dehydrogenase (LDH) and triglycerides, in addition to an increase in glucose, indicative of protective effects on hepatic and muscular injuries. Thus, both maximum tolerable dose (MTD) and no observed adverse effect level (NOAEL) were not determined. The results indicate that long-term intake of high-dose CK might not induce general adverse effects.

Preliminary Study on Seed Germination and Bacterial Bioluminescence for Assessing the Toxicity of Domestic Bentonites (씨앗 발아와 박테리아 발광을 이용한 국내 벤토나이트 독성 평가를 위한 사전 연구결과)

  • Kong, In Chul;Lee, Mun Hee;Jang, Hyun Jin;Lee, Eun Jin;Ko, Kyung Seok;Kang, Il Mo
    • Economic and Environmental Geology
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    • v.49 no.5
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    • pp.411-415
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    • 2016
  • In this preliminary study, we assessed the toxicity of domestic bentonites using environmental toxicity testings of seed germination and bacterial bioluminescence. In cases of tested bulk bentonite samples, following ranges of toxicity were observed: -3 ~ 95% bioluminescence, 7.1 ~ 92.1% Lactuca germination. Similar results were also observed among tested other seeds, except seed Raphanus. No significant correlations between toxicity and metals contents of bentonite extractants were observed throughout this investigation. Interestingly, distinct different effects were observed according to bentonite colors (blue $67{\pm}8.7%$, pink $27{\pm}10.4%$, brown $58{\pm}14.5%$).

Safety Evaluation of Ethanol Extract of Inulae Flos : Single-dose Oral Toxicity Study in Mice (선복화 에탄올 추출물의 급성 독성 연구)

  • Kwon, Da Hye;Kim, Min Young;Hwangbo, Hyun;Ji, Seon Yeong;Park, Cheol;Choi, Yung Hyun;Hong, Su Hyun
    • Herbal Formula Science
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    • v.28 no.2
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    • pp.169-177
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    • 2020
  • Objectives : This experiment was designed to assess the single oral toxicity of Ethanol Extract Inulae Flos (IF) ethanol extracts. IF is one of the important herbs to remove phlegmy which is the viscous turbid pathological product that can accumulate in the body, causing a variety of diseases. Nevertheless, there has been a lack of research on the pharmacology toxicity of IF. Methods : In this study, IF was orally administered to 5 weeks ICR mice as an oral dose of 2,000 or 3,000 or 5,000 mg/kg. The condition of the mice was observed for 14 days and their weights were measured every two days. Results : None of the mice died for 14 days. The abnormal clinical symptoms and anatomical signs of toxicity were not found in any treatment groups. The gain of net body weight was observed. There was also no significant difference in the organ weight. The serum biochemistry and hematological analysis showed a decrease in BUN, red blood cells, white blood cells and platelets although within the normal ranges. Conclusions : These results suggest that the 50% lethal dose of IF is more than 5,000 mg/kg. This could be thought that IF is a safe drug without acute toxicity and side effects. However, IF showed some weight loss and change in blood test, so it will need to be careful when using it for high doses.

Cytoprotective effects of liquiritigenin, a component of licorice, against lead-induced cytotoxicity in PC-12 cells. (PC-12 cell에서 감초성분의 Liquiritigenin이 납에 의해 유도된 세포독성과 nitric oxide production에 미치는 영향)

  • Park, Eun-Young;Park, Sook-Jahr;Lee, Jong-Rok;Jee, Seon-Young;Byun, Sung-Hui;Kim, Sang-Chan
    • The Korea Journal of Herbology
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    • v.22 no.2
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    • pp.17-24
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    • 2007
  • Objectives : Licorice has been commonly used as a detoxification agent. We previously reported that licorice and its component, liquiritigenin, exhibits cytoprotective activity against Pb-induced toxicity. The present study was conducted to evaluate the effect of liquiritigenin on the lead-induced cytotoxicity in PC-12 cells. Methods : PC-12 cells were pre-treated with liquiritigenin, and further incubated with lead 100 ${\mu}M$ for $12^{\sim}48$ hours. The viability of PC-12 cells was measured by MTT assay, and the levels of proteins were analysed by western blot. Results : Severe cytotoxicity was induced and nitric oxide (NO) production was augmented by the exposure of lead. Liquiritigenin protected cells from lead-induced cytoxicity and reduced NO production in a dose-dependent manner. The inhibition of NO production was due to the suppression of iNOS protein via the inhibition of $NF-{\kappa}B$ nuclear translocation, determined by western blot analysis. Conclusions : These results suggest that liquiritigenin may exert cytoprotective effect against lead toxicity by inhibiting NO production.

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Drug Release and Skin Irritancy of Poloxamer Gel Containing Kojic Acid (코지산을 함유한 폴록사머 겔 제제의 약물방출 및 피부자극성)

  • Park, Eun-Woo;Cho, Seong-Wan;Kim, Dong-Sup;Choi, Ki-Hwan;Choi, Young-Wook
    • Journal of Pharmaceutical Investigation
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    • v.28 no.3
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    • pp.177-183
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    • 1998
  • Low toxicity, reverse thermal gelation and high drug loading capabilities suggest that poloxamer 407 gels have great potential as a topical drug delivery system. Kojic acid (KA) is an antimelanogenic agent which has been widely used in cosmetics to whiten the skin color. However, it has the drawbacks of skin irritancy due to its acidic pH. Poloxamer gels of different polymer contents were formulated to overcome the problem and compared to the cream type formulations of either w/o/w multiple emulsion cream or o/w type emulsion cream. Using Franz diffusion cells mounted with a synthetic cellulose membrane (MWCO 12,000), drug release characteristics of the formulations were evaluated by the HPLC assay of KA concentration in the receptor compartment of pH 7.4 phosphate buffered saline solutions. Drug release from w/o/w multiple emulsion cream was controlled by oil membrane, showing the apparent zero order release kinetics. The KA release from the poloxamer gels was also controlled by the gel matrix, showing that drug release increased linearly as KA contents increase, but decreased exponentially as the polymer contents increase. In the skin irritancy test, the primary irritancy index(PII) of poloxamer gel base was lower than those of multiple emulsion cream base and o/w cream. Depending on KA contents or polymer contents in the gel. PH values in poloxamer gels were ranged from 1.3 to 2.0, which are interpreted as low or negligible irritation on skin. There was a good correlation between the log value of flux in drug release and PII value in skin irritation. It was possible to conclude that the poloxamer gels containing KA might be a good candidate for an antimelanogenic topical delivery system by virtue of the controlled release of the drug and the reduced skin irritancy.

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