• Title/Summary/Keyword: subacute toxicities

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A 4-weeks Oral Toxicity of Dangguibohyel-tang in Sprague-Dawley Rats (당귀보혈탕(當歸補血湯)의 SD계 흰쥐에 대한 아급성경구독성시험)

  • Kang, Soon-Ah;Chang, Mun-Seog;Oh, Myung-Sook;Park, Wan-Su;Kim, Won-Nam;Yang, Woog-Mo;Lee, Byong-Hee;Park, Seong-Kyu
    • The Korea Journal of Herbology
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    • v.21 no.2
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    • pp.159-163
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    • 2006
  • Objectives : The subacute toxicity was investigated in Sprague-Dawley rats orally treated with Dangguibohyel-tang (DBT). DBT has been used for anemia, in Korean medicine. Methods : Sprague-Dawley rats were administered orally with DBT at the dosages of 1,000 mg/kg for 14 days. We daily examined number of deaths, clinical signs, body weights and gross findings during the 14 days. Results : There were no clinical signs and pathological changes compared with control group. Body weights were not significantly changed between control and treatment groups. In hematological and biochemical serum parameters, all mean values appear to be within the normal range. Conclusion : These results suggest that DBT dose not induce any significant subacute oral toxicities in Sprague-Dawley rats.

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Subacute Toxicity of DWH-01(Ranitidine : Bismuth subcitrate : Sucralfate) in rats (랫트에 있어서 DWH-01(Ranitidine : Bismuth subcitrate : Sucralfate)의 아급성독성에 관한 연구)

  • 박선미;김형식;김용기;변수현;연제덕;유영효;이병무;이향우
    • YAKHAK HOEJI
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    • v.37 no.4
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    • pp.408-419
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    • 1993
  • Subacute toxicities of DWH-Ol(Ranitidine : Bismuth : Sucralfate=1.5:2:6) were inverstigated in Sprague-Dawley rats. After oral administration of DWH-01 with different dosages of 5 g/kg, l g/kg, and 0.2 g/kg, we examined the number of deaths, general signs, food intake, water intake, body weight and histopatholgical changes for both sexes of rats. During the adminstration period, urinalysis and opthalmological examination were also performed in the treated animals. 1) Animals were all survived for 4 weeks. 2) There were no significant differences in pathological and opthalmological findings between the control and treated animals. 3) There were no significant changes in body weight, food intake and water intake compared with control group. 4) In hematological examination and blood chemical analysis, there was no significant change compared with control group. 5) In histopathological examinations of organs and tissues, there was some hemorrhage in a lung tissue of low dose group, but it was thought to be caused by environmental factor. These data suggest that DWH-01 is not subacutely toxic in Sprague-Dawley rats.

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Subacute Toxicities of All-trans-Retinoic Acid Encapsulated in the Poly(D,L-Lactide) Microspheres

  • Choe, Yong-Du;Park, Gyeong-Sun;Kim, Sang-Yun;Kim, Seon-Hui;Byeon, Yeong-Ro
    • 한국생물공학회:학술대회논문집
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    • 2001.11a
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    • pp.867-870
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    • 2001
  • All-trans-retinoic acid (RA) plays essential roles in the regulation of differentiation and proliferation. It has been proved that RA is effective in the treatments of epithelial and hematologic malignancies. However, in spite of its pronounced effects, the clinical applications of RA are limited due to the retinoid acute resistance. Although RA induces complete remission in a high proportion of the patients of acute promyelocytic leukemia (APL), the cancer was relapsed in many patients after a brief remission in spite of a continued RA treatment. Patients who relapsed from remission that was initially induced by RA had clinically resistant to further RA treatment. That is, specific cytochrome P450 enzymes in the liver were induced by the continuous oral administration of RA, thereby accelerating the metabolism of RA. To overcome this problem, biodegradable microspheres were proposed by us, previously. And, several microsphere formulations for RA delivery have been prepared and studied on their effectiveness. Recently, poly(D,L-lactide) (PDLLA) microsphere formulation was optimized, And, from the animal studies by using a mouse and a rat, it have appeared to be effective on both the inhibition of tumor growth and chemoprevention of a carcinogenesis. In this study, subacute toxicities of the PDLLA microsphere formulation have been investigated as a preclinical test. For the test, the microspheres was injected subcutaneously into the back site of rats, and body weight change, clinical signs, hematological changes, blood biochemistry were evaluated. As a result, severe toxicities such as mortality were observed at the dose of 100mg RA/kg, and toxicities were not observed at the dose of 50mg RA/kg, which is the effective dose against carcinogenesis. Bone fracture, observed at several rats, might be inhibited by treating them with anti-inflammatory drugs.

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Effect of the Water Extract of Cultured Wild Ginseng on the Acute and Subacute Toxicities Induced by Doxorubicin in Mice (산양산삼이 Doxorubicin의 급성 및 아급성 독성에 미치는 영향)

  • Lee, Hyun-Ju;An, Dea-Young;Kim, Ho-Hyun
    • Journal of Physiology & Pathology in Korean Medicine
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    • v.23 no.5
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    • pp.1025-1034
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    • 2009
  • This study was carried out to examine the protective effect of Cultured Wild Ginseng(CWG) on the acute and subacute toxicities induced by doxorubicin(Doxo) in mice. Heart and liver weight was decreased following Doxo administration. In contrast, such a decrease was significantly attenuated by CWG administration. The value of serum CPK in Doxo group was increased compared with normal group. But the value of CWG group were decreased significantly compared with the values of Doxo group in the liver of the Doxo group, cloudy swelling of hepatic cells and narrowing of sinusoids were observed. Whereas in the CWG group, well oriented hepatic cell cords and sinusoids were observed. In the testis of the Doxo group, necrotic and degenerative changes of the seminiferous tubules, especially beneath testicular membrane were observed. But those lesions were alleviated in CWG group. Cross sectional area of testis and diameter of semineferous tubule were significantly increased in CWG group compared with Doxo group. Body weight was reduced in Doxo group compared with normal group. In contrast, such a decrease was significantly attenuated by CWG administration atwa5th day. Spermatogenetic cells in seminiferous tubules were necrotic and desquamated and the cellularity of seminiferous epithelia was reduced in Doxo group. But those lesions were attenuated by CWG administration. Cross sectional area of testis and diameter of seminiferous tubule were significantly increased in CWG group compared with Doxo group. In addition, the increase in lipid peroxidation(LPO) in testis was inaddition, the, iout such a increased was significantly inhibited in CWG group. BrdU labelled cells in the seminiferous tubules were remarkably decreased in Doxo group. Whereas the number of seminiferous tubules labelled with BrdU in spermatogonia was increased by CWG administration. The obtained results suggest that CWG has protective effect on doxorubicin-induced toxicity. This effect might be mediated through the supplementation of vital energy.

Acute/Subacute Toxicity of Nano Calcium (나노 칼슘의 급성/아급성 안전성 평가)

  • Jung, Eun Young;Suh, Hyung Joo
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.44 no.1
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    • pp.29-34
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    • 2015
  • The objective of this study was to obtain data on the safety-in-use of nano calcium as a dietary supplement by assessing its acute and subacute oral toxicities in female and male Sprague-Dawley rats. A single oral dose of 5,000 mg/kg of nano calcium did not result in mortality or significant changes in the general behavior and gross appearance of the internal organs of rats. For subacute toxicity study, nano calcium was administered orally at a dose of 1,000 mg/kg daily for 14 days. There were no significant differences in organ weights between control and treated groups of both sexes. Hematological analysis and blood chemistry revealed no toxic effects of nano calcium. Pathologically, neither gross abnormalities nor histopathological changes were observed. These results show that nano calcium possesses very low toxicity as indicated in a rat model.

Single and 13-week Repeated Dose Toxicity Study of DA-3002, An Authentic Recombinant Human Growth Hormone (천연형 인성장호르몬 DA-3002의 단회 및 13주 반복투여독성연구)

  • 김옥진;강경구;안병옥;백남기;이순복;김원배;양중익
    • Biomolecules & Therapeutics
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    • v.2 no.2
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    • pp.161-172
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    • 1994
  • This study was conducted to examine DA-3002, a biosynthetic human growth hormone, for its acute and subacute toxicities in mice and rats. The drug was administered subcutaneously and orally at a dose level of 1.0, 3.0, 8.9, 26.7 or 80.0 lU/kg once for single dose toxicity and given subcutaneously at a dose level of 0.34, 1.7 or 8.4 lU/kg daily for 13 weeks to investigate repeated dose toxicity. In the acute toxicity study, doses up to 80 lU/kg had no adverse effect on the behavior or body weight gain. Pathological examinations revealed no abnormal changes which could be attributed to toxic effect of DA-3002. In the subacute toxicity study, the growth hormone was tolerated well in broth mice and rats. No drug related deaths occurred and all animals appeared to be normal throughout the dosing period. Increases in body weight gain, food utilisation and absolute organ weights were observed in the rats in the high dose group. Mild changes in the blood chemical parameters were also seen in the treated groups. Histopathologically, however, no abnormal changes were observed in any organ. The changes noted during the treatment periods presumably represent exaggerated pharmacological effects of the growth hormone, and no observed adverse effect level (NOAEL) was considered to be more than 8.4 lu/kg/day.

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Subacute toxicity of cis-Malonato[(4R,5R)-4,5-bis(aminomethyl)-2-isopropyl-1,3-dioxolane]platinum(II)(SKI 2053R) in Beagle Dogs (Beagle Dog에서 cis-Malonato[(4R,5R)-4,5-bis(aminomethyl)-2-isopropyl-1,3-dioxolane]platinum(II)(SKI 2053R)의 아급성독성시험에 관한 연구)

  • Lee, Yong-Soon;Kang, Kyung-Sun;Shin, Dong-Jin;Cho, Jae-Jin;Kim, Hyoung-Ook;Kim, Bae-Hwan;Lim, Yoon-Kyu
    • Toxicological Research
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    • v.8 no.2
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    • pp.235-253
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    • 1992
  • A subacute toxicity study of cis-Malonato[(4R,5R)-4,5-bis(aminomethyl)-2-isopropyl-1,3-dioxolane]platinum(II)(SKI 2053R) was carried out to obtain information on its toxicological profiles, and to determine the maximum tolerated dose in beagle dogs. Four groups of beagle dogs (2M and 2F per group, 0,0.5,1.0,2.0mg/kg/day)were given 15 i.v. injections of SKI 2053R. In order to compare the toxic effects of SKI 2053R with those of cisplatin, one group was treated with cisplatin(0.7mg/kg/day)according to the same treatment schedule. The dosing schedule was divided into 3 courses of 5 consecutive days with 23-day dose-free intervals between each course. After completion of the treatments, remaining dogs were necropsied under established guidelines. Three of four dogs in the high dose group and one of four dogs in the middle dose group treated with SKI 2053R died of hypovolemic shock secondary to hemorrhagic and ulcerative enterocolitis. No toxicity-related mortality occurred in the low dose group of SKI 2053R. No survivor was observed in the group of cisplatin. Clinical signs including vomiting, diarrhea, anorexia and loss body weight were apparent in dogs given either cisplatin or high and middle doses of SKI 2053R. Severe thrombocytopenia and leukocytopenia were observed in the high dose group of SKI 2053R and cisplatin-treatment group, while toxicities as bone marrow suppression were reversible. The significant elevation of serum ALP values in group of SKI 2053R(2.0 mg/kg/day and 1.0mg/kg/day) and cisplatin(0.7mg/kg/day)was observed. Slight proteinuria waa observed in high and middle dose level groups of SKI 2053R. In histopathological examinations, pathological alterations of liver, kidney and spleen were noted dose-dependantly in dogs treated with SKI 2053R, and there was no overt sign of toxicity in low dose group of SKI 2053R. Compared to SKI 2053R, more severe durg-related toxicities occurred in dogs treated with cisplatin. It waw estimated that maximum tolerated dose of SKI 2053R in this treatment schedule was 0.5~0.7mg/kg/day. In conclusion, overall toxic potential of SKI 2053R was approximately 3 times lower than that of cisplatin with respect of lethality.

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Subacute Toxicity of SKI306X, an Antiinflammatory Herbal Extracts, in Rats (생약복합제 SKI306X의 랫드에 대한 4주 경구 반복투여 독성연구)

  • 김훈택;안재석;정인호;김택수;류근호;임광진;조용백;김대기;김환수
    • Biomolecules & Therapeutics
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    • v.4 no.1
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    • pp.19-31
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    • 1996
  • This study was performed to determine the subacute toxicities of SKI306X, an antiinflammatory herbal extract, in rats. SKI306X was administered orally to rats once a day for 4 weeks at doses of 0.3, 1.0, and 3.0 g/kg/ day. Each group consisted of 20 male and 20 female rats, including 5 male and 5 female rats per group for an interim study at the end of 2-week administration and for a 2-week recovery study, respectively. Throughout the study, all rats survived and no adverse clinical signs were observed. Although male rats treated with high dose (3.0 g/kg/day) of SKI306X showed slight loss of body weight (approximately 5%) in comparison with control animals during the administration period, their body weight loss was normally restored during the recovery period. No significant change was found in all hematological parameters of SKI306X-treated groups except for the decreased number of red blood cells in all female groups at the interim study. Statistically significant changes were observed in several blood enzyme levels of SKI306X-treated groups; however, most of these significant changes were within normal range and statistically significant values did not show dose-related responses. In SKI306X-treated groups, the absolute and relative weights of liver, heart, and stomach were statistically different from those of control group, but these differences disappeared at the end of recovery period and also drug-related gross and histopathological findings in these organs were not found. No other drug-related gross and histopathological findings were observed. It is concluded from the results of this study that non-toxic dose of SKI306X was estimated to be between 0.3 and 1.0 g/kg/day and the maximum tolerated dose of SKI306X was assumed to be higher than 3.0 g/kg/day.

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Single and 4-Week Repeated Dose Toxicity Studies of DA-3585, a Recombinant Human Erythropoietin, in Rabbits (사람 적혈구 조혈인자 DA-3585의 토끼에 대한 단회 및 4주 반복투여 독성시험)

  • Cho, Hyeon;Kim, Dong-Hwan;Kang, Kyung-Koo;Baik, Nam-Gi;Kim, Won-Bae
    • Biomolecules & Therapeutics
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    • v.6 no.2
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    • pp.171-181
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    • 1998
  • DA-3585, a biosynthetic recombinant human erythropoietin has been developed as a treatment for anemia associated with chronic renal failure in Dong-A pharmaceutical Co. Ltd. This study was carried out to assess its acute and subacute toxicities in rabbits. DA-3585 was intravenously administered to rabbits at dose levels of 6250, 12500 or 25000 lU/kg for single dose toxicity study and at dose levels of 100, 500 or 2500 lU/kg/day for 4-week repeated dose toxicity study. In the acute toxicity study, dose up to 25000 lU/kg had no adverse effect on the behavior or body weight gain. Pathological examinations revealed no abnormal gross lesions related to DA-3585. In the subacute toxicity study, all animals survived until termination of treatment. DA-3585 had no influence on clinical signs, food and water intake or on body weight changes. Hematological examination showed increases in the number of RBC, hemoglobin contents and hematocrit values with a dose dependent manner in the animals treated with DA-3585. Histopathological examination revealed erythroid hyperplasia in the bone marrow and extramedullary hematopoiesis in the liver. The changes detected in the hematological and histopathological examination presumably represent exaggerated pharmacological effects of erythropoietin. The NOAEL (no-observed-adverse-effect-level) of DA-3585 was estimated to be 100 lU/kg/ day under this study condition.

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