• Biomolecules & Therapeutics
• /
• v.2 no.3
• /
• pp.256-259
• /
• 1994

This study was performed to evaluate the acute toxicity of DA-3030(granulocyte-colony stimulating factor, G-CSF) in mice and rats via intragastrical and intravenous routes. DA-3030(G-CSF) in the acute toxicity study did not induce any toxic signs in the mice and rats in mortalities, clinical findings, body weights and gross findings. It is suggested that LD$_{50}$ values in mice and rats would be >13, 800 $\mu\textrm{g}$/kg in the oral route and >6, 900 $\mu\textrm{g}$/kg in the intravenous route.e.

• Biomolecules & Therapeutics
• /
• v.2 no.3
• /
• pp.281-285
• /
• 1994

Neutropenia is a major dose-limiting factor in cancer chemotherapy diminishing its usefulness and increase patient's susceptibility to infectious disease. Some recombinant human granulocyte colony stimulating factors(rhG-CSFs) are in use to reduce the risk of this serious side effect. In this study, we examined the pharmacological properties of DA-3030, a rhG-CSF expressed in E. coli. DA-3030 100 and $\mu\textrm{g}$/kg, i. v., had no significant effect on the central nervous, gastrointestinal system in mice and cardiovascular system in rabbits, but it slightly inhibited the spontaneous motility of isolated nonpregnant uterus in rats. It also had no influence on excretion of urinary electrolytes. DA-3030 administered for successive 3 days increased the blood WBC count in zymosan air pouch inflammed rats and in normal rats. These results indicate that DA-3030 has little side effects in animals.

• 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.

• Biomolecules & Therapeutics
• /
• v.2 no.3
• /
• pp.270-280
• /
• 1994

This study was conducted to evaluate the repeated dose toxicity of DA-3030, a recombinant human granulocyte colony stimulating factor(rhG-CSF), in rats. DA-3030 was administered intravenously once a day for 4 weeks to 20 males and 20 females per group at doses of 0(control), 115 and 1150 $\mu\textrm{g}$/kg, and to 15 males and 15 females per group at doses of 1.15 and 11.5$\mu\textrm{g}$/kg. After the administration period, 5 males and 5 females per group in the 0,115 and 1150 $\mu\textrm{g}$/kg groups were placed on withdrawal for 2 weeks. Through-out the study, all the rats survived. The administration of DA-3030 induced, a marked increase in the number of peripheral neutrophils, elevation of serum alkaline phosphatase activity, and splenomegaly in the rats of both sexes receiving 115 or 1150 $\mu\textrm{g}$/kg. Histopathologic examination revealed extramedullary granulopoiesis in spleen and liver, and increase in the number of activated macrophages in spleen in rats of both sexes in 115 and 115 $\mu\textrm{g}$/kg groups, and increased M/E ratio in 11.5, 115 and 1150$\mu\textrm{g}$/kg groups. Most of the changes produced by DA-3030 were thought to be attributable to exaggerated pharmacological effect of the drug, and subsided or disappeared after the recovery period. Under the present condition, no effect dose of DA-3030 is estimated at 1.15 $\mu\textrm{g}$/kg/day.

• Applied Biological Chemistry
• /
• v.47 no.3
• /
• pp.315-320
• /
• 2004

The aim of this study was to develop an activator, 3-10 kDa fraction from radish water extracts, that will improve the intestinal function and bowel movement in the colons. Radish water extracts were investigated for their intestinal function effects according to the charcoal meal transit method, employing Balb/c mice: also, their anti-constipation activities were compared utilizing the loperamide-induced constipation method, employing SD rats. The result suggested that the effects of the charcoal meal transit increased remarkably in radish water extract administrated rats in comparison to loperamide administrated rats. Futhermore, the effects of various solvent extracts of radish on charcoal meal transit in Balb/c mice increased remarkably in radish water fraction administrated rats than in different solvent fraction administrated rats. Radish extraction was tested and isolated into 4 groups: below 3 kDa, 3-10 kDa, 10-300 kDa, and over 300 kDa. 3-10 kDa was the most effective on the intestinal function and bowel movement in the colons; also, 3-10 kDa fraction of radish water extraction was found to be the most effective charcoal meal transit. The dry weight and moisture content of feces remarkedly increased in the 3-10 kDa administrated rats group than in the loperamide only group. Experimental results revealed that 3-10 kDa fraction of radish water extract was the most effective on the intestinal function and bowel movement was the crypt epithelial cells that contained more MUC2 in the 3-10 kDa administrated group than the loperamide only group: in addition, the thickness of mucus layer stained with alcian blue was significantly thicker in 3-10 kDa administrated rats than in loperamide administrated rats. Crypt epithelial cells secreted more MUC2 in the 3-10 kDa administrated group than the loperamide only group and the stained cells clearly showed the MUC2 with antibody Biogenex AM358.

• Archives of Pharmacal Research
• /
• v.26 no.8
• /
• pp.612-619
• /
• 2003

In this study, we evaluated the effects of oral administration of DA-8159, a selective phosphodiesterase-5 inhibitor, on the development of pulmonary hypertension (PH) induced by monocrotaline (MCT). Rats were administered either MCT (60 mg/kg) or saline. MCT-treated rats were divided into three groups and received orally administered vehicle, or 1 mg/kg or 5 mg/kg of DA-8159, twice a day for twenty-one days. The MCT group demonstrated increased right ventricular weights, medial wall thickening in the pulmonary arteries, myocardial fibrosis and the level of plasma cyclic guanosine monophosphate (cGMP), along with decreased body weight gains. However, DA-8159 markedly and dose-dependently reduced the development of right ventricular hypertrophy and medial wall thickening. DA-8159 also amplified the increase in plasma cGMP level and significantly increased the level of lung cGMP, compared with the MCT group. Although the body weight gain was still lower from the saline-treated control group, DA-8159 demonstrated a significant increase in body weight gains, in both 1 mg/kg and 5 mg/kg groups, when compared with the MCT group. In myocardial morphology, MCT-induced myocardial fibrosis was markedly prevented by DA-8159. These results suggest that DA-8159 may be a useful oral treatment option for PH.

• Toxicological Research
• /
• v.11 no.1
• /
• pp.69-75
• /
• 1995

The present study was carried out to establish several spermatotoxicity test methods. For this purpose we investigated following parameters in the fertility study of DA-125, a new anticancer agent, in rats: testicular spermatid counts, epididymal sperm counts, daily sperm production rate, sperm morphology, and serum testosterone concentration. Motility and velocity of sperms were also measured using non-treated rats. At 0.3 mg DA-125/kg, spermatids per 1g testis and daily sperm production rate per 1g testis were significantly decreased, when compared with those of control group. Several types of abnormal sperms, such as no head, pin head, double head, hook at wrong angle, no tail, and small sperm, were found in both treated and control groups at a low frequency. Serum testosterone concentration at 0.3 mg DA-125/kg was close to the control value. Sperm motility and velocity measured with non-treated rats were in a good agreement with the results of other investigators. In our study established spermatotoxicity test methods can be used as a tool not only for the close examination of the cause of drug- or chemical-induced infertility, but also for the effective evaluation of reproductive toxicity.

• Archives of Pharmacal Research
• /
• v.17 no.6
• /
• pp.398-404
• /
• 1994

The behavioral response, depamine metabolism, and characteristics of dopamine subtypes after developing the hyperlycemia were studied in the striata of rats. In animals developed hyperglycemia, the on-set duration of cataleptic behavior responded to SCH 23390 injection was delayed abd shortened, respectively. However, the cataleptic response to spiperone occurred significantly earlier in on-set and prolonged in duration. Dopamine metabolites, dihydroxyphenylacetic acid (DDPAC) and homovanillic acid (HVA), were significantly reduced in teh striata of hyeprglycemic rats. However, level of DA was significantly increased. It is noted that the ratios of DOPAC and HVA to DA were decreased, suggesting decreased tumover of DA. The affinity of striatal D-1 receptors was significantly increased without changes in the number of binding sites, while the maximum binding number of D-2 recptors was significantly increased without affecting its affinity in the diabetic rats. These results indicate that the dopaminergic activity in striatia was altered in hyperglycemic rats. Furthermore, it suggests that the upregulation of dopamine receptors might be due to the decreased dopamine matabolism.

• 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.

• Molecular & Cellular Toxicology
• /
• v.5 no.2
• /
• pp.153-159
• /
• 2009

In this study, we assessed the acute and subacute toxicity of Angelica gigas Nakai (A. gigas Nakai) extracts, which are comprised of decursin and decursinol angelate (D/DA) in rats. For the oral acute toxicity test, Sprague-Dawley (SD) male and female rats were gavaged with two doses of D/DA (200 and 2,000 mg/kg body weight) and then observed for any toxic symptoms for 2 weeks. The LD$_{50}$ value for the rats was greater than 2,000 mg/kg body weight for both male and female rats, which indicates that there were no toxic symptoms induced by doses of up to 2,000 mg/kg body weight. For the subacute toxicity study, rats were treated with D/DA at doses of 2 and 20 mg/kg body weight once a day for 30 days. There were no significant changes in body weight and food intake observed during the subacute toxicity study. In addition, no differences were observed between the control and treated groups when urinalysis was conducted or when hematology and biochemical parameters were evaluated. Finally, histopathological examination of the organs did not reveal any lesions in the control or treated groups. Taken together, these findings indicate that D/DA is safe and non-toxic.