• The Korea Journal of Herbology
• /
• v.25 no.2
• /
• pp.137-144
• /
• 2010

Objectives : We investigated genetic toxicity of HMCO5 using the Micronucleus Test in bone marrow cells of mice and Bacterial Reverse Mutation Assay in plate incorporation method according to OECD Guidelines and KFDA Guidelines. Methods : 1. Micronucleus test: The male rats were divided into 5 groups, respectively; G(1), treated with distilled water: G(2), treated with 1250mg/kg HMC05: G(3), treated with 2500mg/kg HMC05, G(4), treated with 5,000mg/kg HMC05; G(5), treated with Cyclophosphamide $H_2O$. Sterilized distilled water and HMC05 were administered for two consecutive days. Cyclophosphamide $H_2O$ was administered once on the day of 2nd administration. 2. Bacterial Reverse Mutation Aassay: Experimental groups were divided into two groups: with S-9mix(+S) or without S-9mix(-S). Each group treated with sterilized distilled water only, HMCO5(62, 185, 556, 1,667, $5,000{\mu}g$/plate) and, positive vehicles(Sodium azide, 2-Aminoanthracene, 4-Nitroquinoline N-oxide, ICR 191), respectively. Results : HMC05 did not show any changes in the number of micronucleated polychromatic erythrocytes(MNPCE) among 200 polychromatic erythrocytes compare to negative control. However, there were significant (p<0.01) increase with CPA in MNPCE. In Bacterial Reverse Mutation Aassay, no significant increases in the number of revertant colonies compared to (삭제) negative control were detected in all concentrations of HMC05. Conclusions : These results indicate that HMC05 did not show any genotoxicity against in Micronucleus test and Bacterial Reverse Mutation Aassay.

• Archives of Pharmacal Research
• /
• v.14 no.1
• /
• pp.73-77
• /
• 1991

The effects of pyridoxine (PN) on rifampicin (RMF) toxicity were investigated by both in vivo and in vitro methods. RMF (30 mg/kg) was injected intraperitoneally and PN(150 mg/kg) was administered orally to rats for 10 consecutive days. After treatment, clinical chemistry and hematologic profiles were measured. RMF and PN plus RMF did not show any adverse effects at this in vivo experimental condition. Thymidine incorporations of mice bone marrow cells were examined in vitro. RMF showed a decrease in thymidine uptake in a dose-dependent manner, but PN showed a reversal of the thymidine uptake suppression caused by RMF (p<0.01). On the other hand, PN showed a decrease in thymidine uptake at a high concentration level.

• Journal of The Korean Society of Clinical Toxicology
• /
• v.6 no.2
• /
• pp.138-141
• /
• 2008

A 47-year-old woman ingested about 12 mg of colchicine with suicidal intent. Colchicine, a highly poisonous alkaloid, is a commonly used treatment for gout, Bechet's disease, and familial Mediterranean fever. Despite the knowledge of its side effects, the risk of a significant overdose is under-appreciated. She suffered from acute multisystem toxicity, including gastrointestinal disorders, bone marrow suppression, alopecia, and probable pancreatitis, but she ultimately recovered with supportive therapy. We report a case of acute colchicine toxicity from a single overdose with a review of the literature.

• Journal of Food Hygiene and Safety
• /
• v.11 no.4
• /
• pp.261-271
• /
• 1996

It has been reported that G009, polysaccharide isolated from Ganoderma lucidum IY009 has various pharmacological effects, such as antinflamatory, antiviral, anticarcinogenic and immunmodulation effects. The purpose of this study was to determine the subacute toxicity of orally administered G009 in Sprague-Dawley rats. Groups of 40 male and 40 female rats were gavaged with 0, 500, 1,000 or 2,000 mg/kg/day for 30 days. No drug-related deaths and clinical morbidities were resulted. There was no drug-related effect on the body weight gain, food consumption and water consumption. Statistically significant changes were observed in several hematological and biochemical parameters of G009-treated groups; however, most of these changes were within normal range and had no relationship to dosage. Urinalysis and bone marrow biopsy showed no remarkable changes in all treated groups. Gross necropsy and hisopathology revealed no evidence of specific toxicity related to G009. Our data indicate that no-observed effect level of G009 is estimated to be above 2,000 mg/kg/day in rats.

• Toxicological Research
• /
• v.20 no.4
• /
• pp.381-389
• /
• 2004

The toxicity of CKD-602 was investigated at doses of 3, 9, and 27 mg/kg in rats, when the same total dose of CKD-602 was administered over 24 hr-continuous infusion or bolus injection. At 3 and 9 mg/kg, the 24-hr infusion group showed a more decreased WBC count on day 3, compared with the bolus group. Administration of CKD-602 caused more toxic effects such as the significant decreases of RBC counts, hematocrit, hemoglobin, and platelet count on day 7 post-administarion in the 24-hr infusion group than in the bolus group. Administration of CKD-602 also caused histopathological changes such as extramedullary hemopoiesis of liver and spleen, hyperplasia of femoral bone marrow, and caecal dilation. These toxic effects were more severe in the 24-hr infusion group than in the bolus injection group, indicating that the toxicity of CKD-602 may be dependant upon the duration of administration.

• Biomolecules & Therapeutics
• /
• v.6 no.2
• /
• pp.182-190
• /
• 1998

DA-3585 is a recombinant human erythropoietin produced by Dong-A pharmaceutical Co. Ltd. using recombinant DNA technique. Recently, recombinant human erythropoietin (rHu-EPO) has been used to treat various types of anemia. In this study, we examined acute and subacute toxicity of DA-3585 in rats. DA-3585 was intravenously administered to rats at dose levels of 0, 6,250, 12,500 and 25,000 lU/kg for single dose toxicity study and at dose levels of 0,100,500 and 2,500IU/kg daily for 4 week-repeated dose toxicity study. In the single dose toxicity study, there were no death, clinical signs and changes in body weight gain related to the treatment. Necropsy revealed no evidence of toxicity related to DA-3585, In the repeated dose toxicity study, all the rats survived throughout the study. There were no treatment-related changes in clinical signs, food and water intake, and body weight. Hematological examination showed increases in the number of erythrocytes, hemoglobin concentration, hematocrit value and mean corpuscular volume, and decrease in the number of platelet in 500 and 2,500 lU/kg dosed groups. Extramedullary hematopoiesis in the spleen and erythroid hyperplasia in the bone marrow were noted as treatment-related histological changes. Toxicologically significant changes were not observed in blood biochemistry, urinalysis, organ weights and in any other examinations. The treatment-related changes observed in this study were hematological or histological changes associated with pharmacological effects of DA-3585. On the basis of the results of this study, LD5n value of DA-3585 was above 25,000 lU/kg and the no-observed-adverse-effect-level was estimated to be 100 lU/kg.

• Korean Journal of Animal Reproduction
• /
• v.18 no.1
• /
• pp.63-70
• /
• 1994

Thirty ewes received typical trauma to their oviducts and uterine horns from surgical embryo collection procedures. Ten percent Dexamethasone was used as an irrigant on the exposed abdominal tissue prior to closing the incision. The treatment group received 17mg colchicine Om! lewe) and the control group was administered a 1.0ml placebo(PSS). Fifteen ewes that were initially treated with 17mg /im colchicine showed acute colchicine toxicity within 2-5 days after initial treatment and were removed from the study. Due to acute colchicine toxicity at 17mg, the colchicine level was lowered to 8, 4 and 2mg(4 ewes/group). Treatments consisted of daily injections of colchicine. One ewe in the 8mg group developed toxicity on day 5. Therefore, ewes were then administered colchicine every other day from day 6 to day 14 postsurgeryat 4 and 2 mg. the second laparotomy was performed 9 weeks after first treatment. Following second laparotomy, the treatment group(n=5) received 4 mg colchicine every day for 14 days and there was no clinical symptoms of colchicine toxicity. The third laparotomy was performed by the same operators 5 weeks after final treatment and the adhesions scored. Adhesion grading was based on a scale of 0-4, with 4 being the most severe. The results of adhesion grading(> 3) at second laparotomy were not significantly different(P>0.05)between the two groups. Adhesion formation observed at third laparotomy showed a reduced, but not significant reduction (P>0.05) in the colchicine-treated ewes when compared with the controls. Ten ewes(5 control and 5 treatment)were examined cytogenetically by bone marrow analysis five days post-treatment. There was no difference(P>0.05)in the incidence of numerical or structural aberrations between the two groups.

• Journal of Physiology & Pathology in Korean Medicine
• /
• v.25 no.1
• /
• pp.109-114
• /
• 2011

Atractylodis Rhizoma Alba is commonly used herbal medicine and it has been known that has immuno-regualtory effects and anti-cancer effects. The inhibition of osteoclastogenesis is essential for the prevention and treatment of osteoporosis. The aim of this study was to evaluate the effects of Atractylodis Rhizoma Alba on osteoclast differentiation in vitro and on resorbing activity of osteoclast. Osteoclast formation was evaluated in bone marrow cells (BMC) in the presence or absence of Atractylodis Rhizoma Alba. The expression of c-fos, tartrate-resistant acid phosphatase (TRAP), OSCAR, DC-STAMP, cathepsin K, MafB and NFATc1 mRNA in osteoclast precursor were assessed by RT-PCR. The levels of TNF receptor-associated factor-6 (TRAF-6), c-fos and NFATc1 protein were assessed by Western blot analysis. Also the correlation with MAPKs and NF-${\kappa}B$ pathways were measured by using Western blot analysis. With bone resorption study, I tried to evaluate the inhibitory effects of Atractylodis Rhizoma Alba on mature osteoclast function. Atractylodis Rhizoma Alba inhibited the RANKL induced osteoclastic differentiation from bone marrow macrophage in a dose dependant manner without cellular toxicity. Gene expression of c-fos and NFATc1 was significantly down regulated with Atractylodis Rhizoma Alba treatment. Atractylodis Rhizoma Alba markedly inhibited the RANKL-induced osteoclastogenesis through suppression of nuclear factor kappa b (NF-${\kappa}B$) pathway, down stream pathway of p38, ERK and JNK pathway. Taken together, I concluded that Atractylodis Rhizoma Alba have beneficial effect on osteoporosis by inhibition of osteoclast differentiation and by inhibition of functioning osteoclast. Thus I expect that Atractylodis Rhizoma Alba could be a treatment option for osteoporosis.

• Toxicological Research
• /
• v.18 no.4
• /
• pp.375-384
• /
• 2002

Repeated-dose toxicity of hyrubicin ID6105, a novel anthrarycline anticancer agent, was investigated in Sprague-Dawley rats. ID6105 was injected intravenously to rats at dose levels of 0.04, 0.2 or 1.0 mg/kg/day for 4 week. As a result, there were no dose-related mortality and specific clinical signs of all animals treated with the drug. However body weight gain of both male and female rats treated with a high dose (l.0 mg/kg/day) of ID6105 significantly decreased compared to control. Interestingly, the numbers of RBC and platelets, and concentration of hemoglobin remarkably increased, while protein synthesis was suppressed, which may be related to the atrophy of spleen, thymus and liver. Moreover there were severe lymphocytic depletion in spleen and thymus as well as decrease in the number of hematopoietic cells in bone marrow. Also, degeneration of cardiac muscles and testicular germinal epithelia were observed. Taken together, it is suggested that Long-term administration of ID6105 at high doses over 0.2 mg/kg/day might cause hematopoietic and male reproductive system injuries, in addition to hepatic dysfunction.

• Journal of Veterinary Clinics
• /
• v.36 no.2
• /
• pp.129-131
• /
• 2019

A 15-year-old intact Yorkshire terrier was presented with anorexia, lethargy, and a pale mucous membrane. A physical examination one year ago revealed right testis mass and subcutaneous petechia. Blood work revealed severe thrombocytopenia and mild anemia, and no abnormalities were found in serum chemistry or ultrasonography. The preoperative serum estrogen concentration was moderately elevated. The enlarged testis was surgically removed. A well-encapsulated mass composed of polyhedral or round with abundant eosinophilic cytoplasm containing fine granular or vacuolation were found in a histological examination of the removed tissue. The nuclei of tumor cells were round, and mitotic figures were low but neoplastic cells showed a mild invasive tendency to adjacent tissues with contained neoplastic cell emboli in one lymphatic lumen. A diagnosis of a malignant Leydig cell tumor was made. The patient recovered from surgery uneventfully, but his condition worsened despite repeated transfusions and supportive therapy, and he was euthanized according to the owner's decision. Leydig cell tumor should be included in estrogen toxicity associated with testicular mass.