• Title/Summary/Keyword: bone marrow toxicity

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Toxicological Evaluation of Medicinal Plants Used for Herbal Drugs (II) -Acute Toxicity and Effects on DNA Biosynthesis in Bone Marrow Cells and Hemoglobin Content in Blood- (한국산 생약의 약리작용 및 독성연구 (제2보) -급성 독성 및 골수세포의 DNA생합성에 미치는 영향-)

  • Chang, Il-Moo;Kim, Young-Soo;Han, Byung-Hoon
    • Korean Journal of Pharmacognosy
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    • v.13 no.1
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    • pp.14-19
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    • 1982
  • Potential toxicity of 15 medicinal plants used for herbal drugs, which were also described as being tonic for hematopoietic system or being toxic for the system in a oriental book 'Dong Ee Bo Gam', were evaluated in mice. Six plants among 15 plants tested appeared to exhibit acute toxicity along with bone marrow depression or with abnormally enhancing the $^3H-thymidine$ incorporation into DNA biosynthesis in bone marrow cells. Six plants were Paeonia albiflora, Pharbitis nil, Cemphalia lapidescens, Scutellaria baicalensis, Akebia quinata and Glycyrriza uralensis.

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Genetic Toxicity Study of YH1715 Series, Antifungal Agents (YH1715계열 항진균제의 유전독성평가)

  • 하광원;오혜영;박장환;허옥순;손수정;한의식;이종영;김소희;강희일
    • Environmental Mutagens and Carcinogens
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    • v.18 no.2
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    • pp.93-97
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    • 1998
  • The results of chromosome aberration test in mammalian cells in culture (Chinese hamster lung fibroblast cells) showed no induction of structural and numerical aberrations by antifungal agents of YH1715 series regardless of metabolic activation. While positive control group (mitomycin C and benzo(a)pyrene) showed structural chromosome aberrations of 37% and 23%, respectively. The in vivo induction of micronuclei was measured in polychromatic erythrocytes in bone marrow of male ddY mouse given YH1715R and YH1729R at 1, 0.5, 0.25 g/kg by p.o. once. After 24 hours, animals were sacrificed and evaluated 40 the incidence of micronucleated polychromatic erythrocytes in whole erythrocytes. Although a positive response for induction of micronuclei in animals treated with mitomycin C demonstrated the sensitivity of the test system for detection of a chemical clastogen, YH1715R did not induce micronuclei in bone marrow of ddY male mice but induced cytotoxicity to bone marrow cells at the highest concentration (1 g/kg, p〈0.05), and YH1729R induced micronuclei in bone marrow of ddY male mice dose dependently (p<0.05) but did not induce cytotoxicity to bone marrow cells.

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Safety Evaluation of Chrysanthemum indicum L. Flower Oil by Assessing Acute Oral Toxicity, Micronucleus Abnormalities, and Mutagenicity

  • Hwang, Eun-Sun;Kim, Gun-Hee
    • Preventive Nutrition and Food Science
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    • v.18 no.2
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    • pp.111-116
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    • 2013
  • Chrysanthemum indicum is widely used to treat immune-related and infectious disorders in East Asia. C. indicum flower oil contains 1,8-cineole, germacrene D, camphor, ${\alpha}$-cadinol, camphene, pinocarvone, ${\beta}$-caryophyllene, 3-cyclohexen- 1-ol, and ${\gamma}$-curcumene. We evaluated the safety of C. indicum flower oil by conducting acute oral toxicity, bone marrow micronucleus, and bacterial reverse mutation tests. Mortality, clinical signs and gross findings of mice were measured for 15 days after the oral single gavage administration of C. indicum flower oil. There were no mortality and clinical signs of toxicity at 2,000 mg/kg body weight/day of C. indicum flower oil throughout the 15 day period. Micronucleated erythrocyte cell counts for all treated groups were not significantly different between test and control groups. Levels of 15.63~500 ${\mu}g$ C. indicum flower oil/plate did not induce mutagenicity in S. Typhimurium and E. coli, with or without the introduction of a metabolic activation system. These results indicate that ingesting C. indicum flower oil produces no acute oral toxicity, bone marrow micronucleus, and bacterial reverse mutation.

Evaluation of the effects of disulfiram, an alcohol-aversive agent with anti-cancer activity, on mouse bone marrow cells

  • Park, Seo-Ro;Joo, Hong-Gu
    • The Korean Journal of Physiology and Pharmacology
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    • v.26 no.3
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    • pp.157-164
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    • 2022
  • Disulfiram (DSF) is an aldehyde dehydrogenase inhibitor. DSF has potent anti-cancer activity for solid and hematological malignancies. Although the effects on cancer cells have been proven, there have been few studies on DSF toxicity in bone marrow cells (BMs). DSF reduces the metabolic activity and the mitochondrial membrane potential of BMs. In subset analyses, we confirmed that DSF does not affect the proportion of BMs. In addition, DSF significantly impaired the metabolic activity and differentiation of BMs treated with granulocyte macrophage-colony stimulating factor, an essential growth and differentiation factor for BMs. To measure DSF toxicity in BMs in vivo, mice were injected with 50 mg/kg, a dose used for anti-cancer effects. DSF did not significantly induce BM toxicity in mice and may be tolerated by antioxidant defense mechanisms. This is the first study on the effects of DSF on BMs in vitro and in vivo. DSF has been widely studied as an anti-cancer drug candidate, and many anti-cancer drugs lead to myelosuppression. In this regard, this study can provide useful information to basic science and clinical researchers.

Green Tea Polyphenol Protection Against 4-Nitroquinoline 1-Oxide-Induced Bone Marrow Lipid Peroxidation and Genotoxicity in Wistar Rats

  • Pandurangan, Ashok Kumar;Periasamy, Srinivasan;Anandasadagopan, Suresh Kumar;Ganapasam, Sudhandiran;Srinivasalu, Shyamala Devi Chennam
    • Asian Pacific Journal of Cancer Prevention
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    • v.13 no.8
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    • pp.4107-4112
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    • 2012
  • 4-Nitroquinoline 1-oxide (4-NQO) a potent oral carcinogen, widely used for induction of oral carcinogenesis, has been found to induce lipid peroxidation in vivo and in vitro. Green tea contains a high content of polyphenols, which are potent antioxidants. Thus green tea polyphenols (GTP) might be expected play a protective role against 4-NQO induced lipid peroxidation and bone marrow toxicity. In the present study, a dose of 200 mg of GTP/kg b.wt/day was given orally for a week, simultaneously animals received 0.2 ml of 0.5% 4-NQO in propylene glycol (5 mg/ml) injected intramuscularly for three times/week. Oxidants and antioxidants such as malendialdehyde (MDA) and thiols, glutathione peroxidase (GPx), glutathione reductase (GR), superoxide dismutase (SOD) and catalase (CAT) were significantly decreased in 4-NQO induced animals except MDA, and these parameters were brought back to near normalcy on treatment with GTP. The results suggest that GTP treatment offers significant protection against 4-NQO induced lipid peroxidation and bone marrow toxicity and might be a promising potential candidate for prevention of mutations leading to cancer.

A Study of Gastrointestinal and Bone Marrow Adverse Events after Administration of Various Chemotherapeutic Agents in Canine Malignant Tumor Patients

  • Ji, Na-Ni;Song, Joong-Hyun;Hwang, Tae-Sung;Lee, Hee-Chun;Yu, Do-Hyeon;Jung, Dong-In
    • Journal of Veterinary Clinics
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    • v.36 no.1
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    • pp.30-37
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    • 2019
  • The purpose of this present study was to objectively evaluate gastrointestinal and bone marrow AEs after administration of various chemotherapeutic agents in canines with malignant tumors, using the Veterinary Cooperative Oncology Group-Common Terminology Criteria for Adverse Events (VCOG-CTCAE), which includes descriptive terminology used for adverse events (AEs) reported in dogs and cats. The medical records of 42 dogs with malignant tumor that underwent chemotherapy were reviewed retrospectively. There were no significant differences in the prevalence of gastrointestinal AEs among the 5 chemotherapeutic agents (vincristine, cyclophosphamide, doxorubicin, lomistine, and carboplatin). The prevalence of bone marrow AEs was significantly higher after administration of lomustine than after administration of vincristine or doxorubicin. Grade 1 AEs of the gastrointestinal tract and bone marrow were most often observed after administration of various chemotherapeutic agents. Delayed and cumulative myelosuppression of lomustine in some dogs receiving regular blood examination were identified. The findings of this study will help predict possible gastrointestinal and bone marrow AEs due to the use of chemotherapeutic agents to treat canines with malignant tumors.

The Preventive Effect of Angelica gigas Nakai Extract and Green Coffee BeanExtract on Bone Marrow Toxicity Induced by Benzene (Benzene으로 유도한 골수독성에 대한 참당귀 추출물과 커피 생두 추출물의 예방효과 연구)

  • Eun-Bi Lee;Seo-Kyung Lee;Ye-Jin Hwang;Hyun-Woo Kim;Jae-Seon Kang
    • Journal of Life Science
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    • v.34 no.9
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    • pp.620-631
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    • 2024
  • Bone marrow toxicity is a side effect of chemotherapy with anticancer drugs or the exposure to chemicals, such as benzene. When myelotoxicity occurs, the number of white blood cells decreases, which reduces immune functioning and increases the risk of infection or the development of tumors. Angelica gigas Nakai extract (AGNEX) and green coffee bean extract (GCBE) have many effects, such as anti-cancer and antioxidant effects, as well as effects on the immune functioning. In this experiment, the preventive effect of AGNEX and GCBE against benzene-induced bone marrow toxicity was confirmed in Sprague Dawley rats (SD rats) in vivo. Benzene (1 ml/kg mixed with corn oil 1:1) was intraperitoneally administered to SD rats (six weeks, N = 9/group) once a day, and AGNEX (12 mg/kg) and GCBE (6, 12, and 24 mg/kg) were administered orally daily for five weeks. To determine the preventive effect, AGNEX (12 mg/kg) and GCBE (6, 12, and 24 mg/kg) were administered orally before the administration of benzene. Consequently, AGNEX 12 mg/kg and GCBE 12 mg/kg were effective at reducing leukocytes and lymphocytes, specifically granulocyte. Additionally, the treatment also showed protective effects specifically on spleen and liver weight changes and spleen damage. Through this protective effect, AGNEX and GCBE were confirmed to prevent bone marrow toxicity by enhancing the functioning of the immune system.

Combined Genotoxic Effects of Aflatoxin B1, Ochratoxin A and Zearalenone in Rat Bone Marrow and Blood Leukocytes

  • Tigran, Harutyunyan;Anna, Karapetyan;Galina, Hovhannisyan;Rouben, Aroutiounian
    • Korean Journal of Environmental Biology
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    • v.31 no.3
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    • pp.189-191
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    • 2013
  • Mycotoxins such as aflatoxin B1 (AFB1), ochratoxin A (OTA) and zearalenone (ZEA) are widespread contaminants of food and feedstuffs. It is very likely, that humans and animals are always exposed to mixtures of mycotoxins rather than to individual compounds. Therefore, risk assessments should consider mixture toxicity data. In the present study the combination of AFB1, OTA and ZEA was tested for genotoxicity in rat bone marrow and blood leukocytes after 15, 30 and 60 days treatment. The level of DNA damage was determined by the comet assay. The tail intensity and Olive tail moment in leukocytes and bone marrow cells were significantly higher than in controls. At the same time, the level of DNA damage in bone marrow cells was higher than in leukocytes. The data suggests that prolonged exposure to mycotoxins combination through food consumption can induce DNA damage contributing to the harmful effects in vivo.

Effect of Ampelopsis radix on the Toxicity of Adriamycin (Adriamycin의 독성 발현에 미치는 백렴(Ampelopsis radix)의 영향)

  • Kim, Dong-Seok;Lee, Seong-Ho;Jeong, Yeon-Bong
    • The Korean Journal of Food And Nutrition
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    • v.7 no.3
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    • pp.232-238
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    • 1994
  • Adriamycin is a major cancer chemotherapeutic agent against a me range of human neoplasms. However, its clinical application is limited since It has a variety of side effects, bone marrow suppression and cardiotoxity, and this toxicity appears by free radical. This study investigated the effect of Ampelopsis radix on the toxicity of adriamycin. The methanol fraction reduced slightly adriamycin induced lipid peroxidation and superoxide production at the dose of 50mg /kg. 1.p., respectively. During the adriamycin administration. Protein bound-SH, nonprotein bound-SH, and glutathione-5-transferase did not change, but methanol fraction treated group were markedly increase. These results indicated that Ampelopsis radix has a major influence on the thiol group and related enzyme activity on the antioxidative effects.

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Computerized Image Analysis of Micronucleated Reticulocytes in Mouse Bone Marrow (컴퓨터 이미지 분석법을 이용한 마우스 골수세포에서 소핵의 계수)

  • 권정;홍미영;고우석;정문구;이미가엘
    • Toxicological Research
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    • v.18 no.4
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    • pp.369-374
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    • 2002
  • The present study was performed to validate an automated image analysis system (Loats Automated Micronucleus Scoring System) for the mouse bone marrow micronucleus assay, comparing with conventional microscopic scoring. Two studies were conducted to provide slides for a comparison of micro-nucleated polychromatic erythrocytes (MNPCEs) values collected manually to those collected by the auto-mated system. Test article A was used as an example of a compound negative for the induction of micronuclei and test article B was wed as a micronucleus-inducing agent to elicit a positive response. Cyclophosphamide was included to provide an positive control in two studies. Bone marrow samples were collected 24 h after administration of test article A and B in male ICR mice. The cells were fixed with absolute methanol and stained with May-Grunwald and Giemsa. The number of MNPCEs was determined by the analysis of 1000 total PCEs per bone marrow sample. In addition to micronucleus scoring, an index of bone marrow toxicity based on PCE ratio (% of PCEs to total erythrocytes) was determined for each sample. The automated and manual scoring was similar when the MNPCEs incidence induced by each test article was less than 10. However manual scoring was able to effectively enumerate micronucleated PCEs in mouse bone marrow when MNPCEs incidence was more than 10, such as cyclophosphamide treatment. Conversely, PCE ratio was superior in computer-assisted image analysis. Taken together, it is suggested that improvement of the automated image analysis may be necessary to render the automatic scoring as sensitive as manual scoring for routine counting of micronuclei, especially because it is superior in objectivity and high throughput scoring.