• Title/Summary/Keyword: bone marrow toxicity

Search Result 108, Processing Time 0.038 seconds

Single Dose Intravenous Toxicity Study of A New Anthracycline Anticancer Agent (DA-125) in Rats and Mice (새로운 안트라사이클린계 항암제 DA-125의 랫드 및 마우스에서의 정맥투여 급성 독성시험)

  • 신천철;송시환;서정은;강부현;김원배;한상섭
    • Biomolecules & Therapeutics
    • /
    • v.8 no.1
    • /
    • pp.84-92
    • /
    • 2000
  • This Study was conducted to assess the single dose toxicity of DA-125, a new anthracycline anti-cancer agent, in rats and mice. The Drug was administered once intravenously to both sexes of rats and mice. Then followed a 14-day period of observation. The $LD_{50}$ Values (95% confidence limit) were estimated to be 60.9 mg/kg (57.5~64.3 mg/kg) for male rats and 60.2 mg/kg (56.2~64.5 mg/kg) for female rats, and 85.8 mg/kg (81.0~90.9 mg/kg) for male mice and 84.5 mg/kg (78.2~91.9 mg/kg) for female mice. Both sexes of rats and mice given the drug revealed the clinical sign of decreased locomotor activity, emaciation, hair loss, red-dish brown urine, salivation, and watery diarrhea. In addition, body weight from the next day to the 7th day tended to be decreased slightly in rats and mice treated with DA-125. Death occurred from the next day after administration to the 12th day. Macroscopically, congestion of gastrointestinal organ, lung, and adrenal glands were found in both sexes on the dead rats and mice. Histopathological examination of dead rats manifested atrophy of spleen, hypoplasia of bone marrow, hypcplasia and necrosis of lymphocyte in thymus, atrophy of villi in small intestine (duodenum, jejunum, and ileum), hyperplasia of granular epithelium in small intestine, degeneration of germinal epithelium in testis, defer oration of tubular epithelium in kidney, and vacuolation and myolysis of myocardium in heart. Histopathological examination of dead mice revealed hypoplasia of spleen and mesenteric lymph node, local necrosis of liver, atrophy of villi in small intestine, hyperplasia of glandular epithelium in small and large intestine, degeneration of tubular in kidney, degeneration of germinal cells in testis, and slight vacuolar degeneration of myocardium in heart.

  • PDF

Evaluation of Genotoxicity and 14-day Repeat Dose Toxicity of Water Extract of the Mixture of Natural Plants, Anemarrhena and Phellodendron (천연식물자원 지모와 황백피 혼합 수추출물의 안전성평가)

  • Chung, Young-Shin;Park, Cheol-Beom
    • Journal of Food Hygiene and Safety
    • /
    • v.29 no.4
    • /
    • pp.383-390
    • /
    • 2014
  • The safety of a new natural plant composition (ADP) was assessed on the genotoxicity study and 14-day repeat dose toxicity study. ADP contains a mixed water extract obtained from the mixture of Phellodendron cortex (Phellodendron amurense) and Anemarrhena rhizoma (Anemarrhena asphodeloides), and poses the contractile properties mediated by alpha-adrenoceptor of the prostate and urethra as well as antioxidant and anti-inflammatory properties. In order to evaluate genetic safety, in vivo micronucleus test was performed in ICR mice orally administered with three dose levels of 1250, 2500, 5000 mg/kg body weight, and vehicle and positive control. In the 14 days study, Sprague-Dawley rats were treated with ADP at the dose levels of 500, 1000, 2000 mg/kg once a day, and clinical signs, body weights, hematology, serum biochemistry, necropsy findings and organ weights were monitored and examined. In experimental results, ADP treatment, compared with vehicle control, did not induce the micronucleated erythrocytes from mouse bone marrow. In the 14 days study, any significant and toxicological differences in all measurements of parameters were not observed in ADP treatment groups of animals, compared with vehicle treatment. The No-Observed-Adverse-Effect-Level (NOAEL) of ADP in the 14 days study was determined to be greater than 2000 mg/kg/day in both sexes.

Potential ameliorative effects of bilberry (Vaccinium myrtillus L.) fruit extract on cisplatin-induced reproductive damage in adult male albino rats

  • Fatma B. Mossa;Nadia Bakry;Mamdouh Rashad El-Sawi
    • Clinical and Experimental Reproductive Medicine
    • /
    • v.51 no.3
    • /
    • pp.192-204
    • /
    • 2024
  • Objective: Cisplatin (CP) is a widely used chemotherapeutic agent, but its severe side effects impact testicular function. We investigated the potential protective effects of bilberry extract against CP-induced testicular toxicity. Methods: Forty adult male albino rats were divided into four groups. Control animals received a single oral dose of 0.9% saline. Bilberry-treated rats received oral bilberry extract (200 mg/kg body weight [BW] dissolved in 1 mL of saline) daily for 10 consecutive days. CP-treated animals were administered a single intraperitoneal dose (7.5 mg/kg BW). Finally, a bilberry+CP group received oral bilberry extract (200 mg/kg BW) daily for 10 consecutive days, with one intraperitoneal dose of CP (7.5 mg/kg BW) on day 2. We assessed sperm count, motility, viability, and abnormalities, along with testis weight, testis weight-to-BW ratio, antioxidant activity, levels of oxidative stress markers (malondialdehyde [MDA] and hydrogen peroxide [H2O2]), sex hormones (follicle-stimulating hormone [FSH], luteinizing hormone [LH], and testosterone), and apoptotic and anti-apoptotic markers, and DNA damage. Testicular tissue underwent histopathological examination. Results: Among CP-treated rats, significantly lower values were observed for testis weight; testis weight-to-BW ratio; levels of FSH, LH, testosterone, superoxide dismutase, catalase, glutathione S-transferase, glutathione, and B-cell lymphoma 2; and sperm count, motility, and proportion of normal sperm. CP administration was associated with higher MDA, H2O2, p53, Bax, cytochrome c, caspase 9, and caspase 3 levels, along with elevated tail moment. However, bilberry extract administration significantly improved all altered parameters. Conclusion: Bilberry treatment demonstrated protective effects and reduced CP-induced testicular toxicity via antioxidant activity and cytoprotection.

Initial Risk Assessment of Acetanilide in OECD High Production Volume Chemical Program

  • Park, Hye-Youn;Park, Yoonho;Sanghwan Song;Kwon, Min-Jeoung;Koo, Hyun-Ju;Jeon, Seong-Hwan;Na, Jin-Gyun;Park, Kwangsik
    • Toxicological Research
    • /
    • v.18 no.1
    • /
    • pp.13-22
    • /
    • 2002
  • In Korea, 2,320 tonnes of acetanilide were mostly wed as intermediates for synthesis in phar-maceuticals or additives in synthesizing hydrogen peroxide, varnishes, polymers and rubber. Only small amount of 120 kg were wed as a stabilizer for hydrogen peroxide solution for hair colouring agents in 1998. Readily available environmental or human exposure data do not exist in Korea at the present time. However, potential human exposures from drinking water, food, ambient water and in work places are expected to be negligible because this chemical is produced in the closed system in only one company in Korea and the processing factory is equipped with local ventilation and air filtering system. Acetanilide could be distributed mainly to water based on EQC model. This substance is readily biodegradable and its bioaccumulation is low. Acute toxicity of acetanilide is low since the L $D_{50}$ of oral exposure in rats is 1,959 mg/kg bw. The chemical is not irritating to skin, but slightly irritating to the eyes of rabbits. horn repeated dose toxicity, the adverse effects in rats were red pulp hyperplasia of spleen, bone marrow hyperplasia of femur and decreased hemoglobin, hematocrit and mean corpuscular hemoglobin concentration. The LOAEL for repeated dose toxicity in rats was 22 mg/kg/day for both sexes. Acetanilide is not considered to be genotoxic. In a reproductive/developmental toxicity study, no treatment-related changes in precoital time and rate of copulation, impregnation, pregnancy were shown in all treated groups. The NOAELs for reproduction and developmental toxicity (off-spring toxicity) are considered to be 200 mg/kg bw/day and 67 mg/kg bw/day, respectively. Ecotoxicity data has been generated in a limited number of aquatic species of algae (72 hr- $E_{b}$ $C_{50}$; 13.5 mg/l), daphnid (48hr-E $C_{50}$ > 100 mg/l) and fish (Oryzias latipes, 96hr-L $C_{50}$; 100 mg/l). Form the acute toxicity values, the predicted no effect concentration (PNEC) of 0.135 mg/1 was derived win an assessment factor of 100. On the basis of these data, acetanilide was suggested as currently of low priority for further post-SIDS work in OECD.in OECD.D.

Effect of Saururus Chinensis in RANKL-induced Osteoclast Differentiation (삼백초 추출물이 뼈 파괴세포 분화에 미치는 효과)

  • Kim, Jung Young;Hyuk, Jungjong;Lee, Myeung Su;Lee, Chang Hoon;Kim, Yun Kyung;Jeon, Byung Hoon;Kwak, Han Bok;Kim, Ju-Young;Choi, Min-Kyu;Kim, Jeong Joong;Oh, Jaemin
    • Journal of Physiology & Pathology in Korean Medicine
    • /
    • v.26 no.6
    • /
    • pp.869-873
    • /
    • 2012
  • Balance between bone-forming osteoblasts and bone-resorbing osteoclasts is important in bone homeostasis. Unusual balance between bone-forming osteoblasts and bone-resorbing osteoclasts leads to bone diseases, such as osteoporosis. Saururus chinensis has been widely used in oriental medicine. Saururus chinensis has been known that has antioxidant and anticancer effect. But, the effect of Saururus chinensis in osteoclast differentation remains unknown. We examined the effect of Saururus chinensis in receptor activator of nuclear factor-${\kappa}B$ ligand (RANKL)-induced osteoclast differentiation. From the results of our study, we found that saururus chinensis clearly inhibited RANKL-induced osteoclast differentiation in bone marrow macrophages (BMM) in a dose dependent manner without toxicity. Saururus chinensis inhibited the phosphorylation of JNK, P38, AKT, and ERK induced by RANKL. The mRNA expression of NFATc1, TRAP, and OSCAR induced by RANKL was inhibited by Saururus chinensis treatment. Moreover Saururus chinensis suppressed the protein expression of c-Fos and NFATc1 in BMMs treated with RANKL. These results suggest that Saururus chinensis may be a useful drug in the treatment of bone-related disease.

Fertility preservation for patients with hematologic malignancies: The Korean Society for Fertility Preservation clinical guidelines

  • Lee, Dong-Yun;Kim, Seul Ki;Kim, Miran;Hwang, Kyung Joo;Kim, Seok Hyun
    • Clinical and Experimental Reproductive Medicine
    • /
    • v.44 no.4
    • /
    • pp.187-192
    • /
    • 2017
  • Although the survival rate of hematologic malignancies in young patients is very high, cytotoxic therapies such as chemotherapy and total body irradiation therapy can significantly reduce a patient's reproductive capacity and cause irreversible infertility. Early ovarian failure also commonly occurs following additional cancer treatment, bone marrow transplantation, or autologous transplantation. Because the risk of early ovarian failure depends on the patient's circumstances, patients with a hematologic malignancy must consult health professionals regarding fertility preservation before undergoing treatments that can potentially damage their ovaries. While it is widely known that early menopause commonly occurs following breast cancer treatment, there is a lack of reliable study results regarding fertility preservation during hematologic malignancy treatment. Therefore, an in-depth discussion between patients and health professionals about the pros and cons of the various options for fertility preservation is necessary. In this study, we review germ cell toxicity, which occurs during the treatment of hematologic malignancies, and propose guidelines for fertility preservation in younger patients with hematologic malignancies.

Genotoxicity of Zizyphi Spinosi Semen in Bacterial Reverse Mutation (Ames) Test, Chromosomal Aberration and Micronucleus Test in Mice

  • Zhang, Mei-Shu;Bang, In-Seok;Kang, Chang-Su;Park, Cheol-Beom
    • Journal of Food Hygiene and Safety
    • /
    • v.27 no.2
    • /
    • pp.141-145
    • /
    • 2012
  • Zizyphi spinosi semen (Z. spinosi) has been used in traditional Chinese medicine for the treatment of rheumatoid arthritis and wounds. However, toxicity in high doses was often observed due to the presence of alkaloids. This study was conducted to investigate the potential genotoxicity of Z. spinosi in vitro and in vivo. This was examined by the Bacterial reverse mutation (Ames) test using Salmonella typhimurium TA98, TA100, TA1535, TA1537 and Escherichia coli WP2uvrA, Chromosomal aberration was investigated using Chinese hamster lung cells and the micronucleus test using mice. Z. Spinosi did not induce mutagenicity in the Ames test, and it did not produce chromosomal aberration in Chinese hamster lung cells with and without metabolic activation, nor in the micronucleated polychromatic erythrocytes in the bone marrow cells in mice. Based on these results, it is concluded that Z. spinosi does not have mutagenic potential under the conditions examined in each study.

Further Study on Pemetrexed based chemotherapy in Treating Patients with Advanced Gastric Cancer (AGC)

  • Liu, Jin;Huang, Xin-En;Feng, Ji-Feng
    • Asian Pacific Journal of Cancer Prevention
    • /
    • v.15 no.16
    • /
    • pp.6587-6590
    • /
    • 2014
  • Objective: To further observe the efficacy and safety of pemetrexed, combined with Irinotecan or oxaliplatin or cisplatin in treating patients with advanced gastric cancer as second-line or third-line chemotherapy. Methods: From September 2013 to February 2014 we recruited 50 patients with advanced gastric cancer, with stage IV disease or postoperative recurrence, or unresectable. Then treated with pemetrexed based chemotherapy. After two cycles of treatment, efficacy and toxicity were evaluated. Results: Pemetrexed based chemotherapy was used as second-line in 33 patients, RR(CR+PR) is 41.2%. And achieved 36.4% when used as third-line. Overall response rate of 50 patients treated with Pemetrexed based treatment was 38% (CR+PR). Treatment related side effects were bone marrow suppression, vomiting, hepatic dysfunction and malaise.No treatment related death occurred. Conclusions: Treatment with pemetrexed based chemotherapy is active and is well tolerated in patients with advanced gastric cancer.

Anti-tumor and Chemoprotective Effect of Bauhinia tomentosa by Regulating Growth Factors and Inflammatory Mediators

  • Kannan, Narayanan;Sakthivel, Kunnathur Murugesan;Guruvayoorappan, Chandrasekaran
    • Asian Pacific Journal of Cancer Prevention
    • /
    • v.16 no.18
    • /
    • pp.8119-8126
    • /
    • 2016
  • Cancer is a leading cause of death worldwide. Due to the toxic side effects of the commonly used chemotherapeutic drug cyclophosphamide (CTX), the use of herbal medicines with fewer side effects but having potential use as inducing anti-cancer outcomes in situ has become increasingly popular. The present study sought to investigate the effects of a methanolic extract of Bauhinia tomentosa against Dalton's ascites lymphoma (DAL) induced ascites as well as solid tumors in BALB/c mice. Specifically, B. tomentosa extract was administered intraperitonealy (IP) at 10 mg/kg. BW body weight starting just after tumor cell implantation and thereafter for 10 consecutive days. In the ascites tumor model hosts, administration of extract resulted in a 52% increase in the life span. In solid tumor models, co-administration of extract and CTX significantly reduced tumor volume (relative to in untreated hosts) by 73% compared to just by 52% when the extract alone was provided. Co-administration of the extract also mitigated CTX-induced toxicity, including decreases in WBC count, and in bone marrow cellularity and ${\alpha}$-esterase activity. Extract treatment also attenuated any increases in serum levels of $TNF{\alpha}$, iNOS, IL-$1{\beta}$, IL-6, GM-CSF, and VEGF seen in tumor-bearing hosts. This study confirmed that, the potent antitumor activity of B.tomentosa extract may be associated with immune modulatory effects by regulating anti-oxidants and cytokine levels.

A Oriental Medical Study on the Castanea mollissima Bl. (율(栗)에 대(對)한 한의학적(韓醫學的) 문헌고찰(文獻考察))

  • Lee Soo-Jin;Kim Myung-Dong;Nam Young-Jae
    • Journal of Society of Preventive Korean Medicine
    • /
    • v.4 no.1
    • /
    • pp.122-131
    • /
    • 2000
  • This dissertation is try to figure out why chestnut belongs to kidney channel, from the viewpoint of five elements theory. After studying chestnut's property, flavor, channel tropism, main cure ability, prescriptions, shape, sweet, and prohibitions, I came to the following results. 1. Property of chestnut is warm and has no toxicity, so it is less related than kidney property. 2. Flavor of chestnut is salty and sweet, so it has some relation to kidney and spleen properties. 3. Channel tropism of chestnut enters mainly into kidney channel, and then spleen and stomach channels. 4. Chestnut controls kidney function of storing the essence of life, determining the condition of bone and marrow, conduction water metabolism, affecting reasoning activity, and controls activity of nine openings of body. It also has effects on functions of spleen, intestines and stomach. 5. Prescriptions including chestnut is similar to that of human brain, it is possible to reason out that chestnut has some relation to human brain. 7. As flavor of chestnut flower is similar to that of spermatic fluid, so it has som relation to kidney property. 8. As chestnut has property of blocking qi and it causes spleen, stomach and colon system to be confused, so it is suggested that persons with weakende spleen and stomach be not allowed to take in.

  • PDF