• Environmental Analysis Health and Toxicology
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• v.18 no.3
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• pp.231-235
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• 2003

To determine whether or not bisphenol A affects the Immune system, female ICR mice were treated bisphenol A (BPA) orally at the doses of 100, 500 and 1,000 mg/kg for 30 consecutive days. Four days before enumerating Plaque -forming cells (PFCs) mice were immunized intraperitoneally with sheep red blood cells (SRBCs). The spleen cellularity and PFC/spleen were significantly reduced by 30-day exposure to BPA (1,000 mg/kg/day), but the PFC/10$\^$6/ spleen cells was slightly decreased.. When splenocytes isolated from the mice exposed to BPA for 30 days were cultured in the presence of LPS, Con A or PHA with IL-2, the lymphocyte proliferation ex vivo was not significantly suppressed by BPA. Our present results indicated that 30-day exposure of mice to BPA might have mild immunotoxic potential.

• Biomolecules & Therapeutics
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• v.4 no.2
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• pp.138-147
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• 1996

DWP401, a recombinant human epidermal growth factor, was subcutaneously administered to ICR mice at the dose levels of 0, 0.04, 0.2 and 1.0 mg/kg/day (15rats/sex/group) in order to evaluate the subchronic toxicity. General observations, examinations for food and water consumption, ophthalmoscopy and urinalysis were carried out during the study. For the complete gross and microscopic examinations, 10 mice/ sex/group were sacrificed at the ends of the dosing period, and the remaining animals were sacrificed with a 5 week recovery period. Examinations for hematology and blood biochemistry were also carried out at the time of recovery period. Based on the results, it was thought that the target tissue or organs were mesothelial cell, injection site, spleen, adrenal gland, ovary and transitional epithelial cell of urinary tract, and no observed toxic level of DWP401 was 0.04 mg/kg while definite toxic dose level might be 0.2 mg/kg.

• Toxicological Research
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• v.18 no.2
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• pp.205-213
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• 2002

This study was undertaken to develop a subacute murine model for predicting occurrence of systemic anaphylaxis and to evaluate efficacy of various immunological parameters as the monitoring indices for the occurrence of anaphyalxis. The murine anaphyalxis model was developed through intraperitoneally sensitizing 100 $\mu\textrm{g}$ ovalbumin (OVA) in the presence of 1 mg alum and 300 ng cholera toxin twice a week interval followed by challenging 500 $\mu\textrm{g}$. OVA intravenously. Typical anaphylaxis symptoms were demonstrated at the both BALB/c mice, a strain prone to type-2 response, and C57BL/6 mice. a strain prone to type-1 response. Level of plasma histamine was approximately 50-fold or 30-fold higher in the mice sensitized with OVA than the mice sensitized with alum plus cholera toxin or the saline-treated mice after OVA challenge, respectively. Sensitization and challenge with OVA significantly enhanced plasma leukotriene $B_4$ level but not IgE levels in comparison with the control mice, which indicated the role of leukotriene $B_4$ for progression of anaphyalxis. Furthermore, among mice suffered from anaphylaxis, levels of OVA-specific IgGl were significantly higher in the BALB/c mice than in the C57BL/6 mice, which implied the genetic susceptibility for the induction of systemic anaphylaxis. Conclusively, simultaneous evaluation of histamine, leukotriene $B_4$, and allergen-specific IgG isotype may serve as more efficient monitoring tool for vaccine-related anaphyalxis.

• Journal of The Korean Society of Clinical Toxicology
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• v.17 no.2
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• pp.79-85
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• 2019

Purpose: The purpose of this study is to evaluate the effectiveness of vitamin B12 treatment in subacute combined degeneration (SCD) caused by nitrous oxide (N₂O) abuse. Methods: Relevant literature was accessed through PubMed, EMBASE, Scopus, and KoreaMed. All the literature that was relevant to human use of vitamin B12 treatment for SCD caused by N₂O abuse was included. Case reports were excluded if the treatment regimens were not precisely described. The literature search was conducted by two investigators during September 2019 for the final publication period. The languages of the publications were restricted to English and Korean. Results: Twenty-three published articles that contained 24 cases were included. Sixteen cases among them were treated with intramuscular vitamin B12 of 1 mg/day and the rest received different doses or routes. Although most cases described significant clinical improvements, one case showed no beneficial effect due to the patient's noncooperation. Another case showed adverse events, including spinal myoclonus, following vitamin B12 therapy. Conclusion: Vitamin B12 has been broadly used for the treatment of SCD caused by N₂O abuse. However, most of the relevant studies were case reports that reported various regimens of vitamin B12 administration. Further studies are needed to establish a standard regimen of vitamin B12 because the incidence of N₂O abuse may increase in South Korea.

• 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.

• The Journal of Internal Korean Medicine
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• v.18 no.1
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• pp.231-241
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• 1997

The purpose of this research was to investigate effect of water extract of Euphorbiae Pekinensis Radix and Moutan Cortex Radicis on the proliferation of human cancer cell-lines. The effects of Euphorbiae Pekinensis Radix and Moutan Cortex Radicis on the proliferation of A431, HeLa, MOLT-4, K562 cells, Balb/c 3T3 cells, mouse thymocytes, splenocytes and human lymphocytes were estimated by MTT colorimetric assay. The results were as follows; 1. In proliferation of A431, HeLa, MOLT-4 and K562 cell-lines, Euphorbiae Pekinensis Radix and Moutan Cortex Radicis inhibited the proliferation of K562 cells. 2. In the combined effect of Euphorbiae Pekinensis Radix and mitomycin C, Moutan Cortex Radicis and mitomycin C, all herbs stimulated the proliferation of MOL T-4 cells. 3. Euphorbiae Pekinensis Radix and Moutan Cortex Radicis did not inhibited the proliferation of Balb/c 3T3 cells. 4. Euphorbiae Pekinensis Radix and Moutan Cortex Radicis stimulated the proliferation of mouse thymocytes. 5. Euphorbiae Pekinensis Radix and Moutan Cortex Radicis stimulated the proliferation of mouse splenocytes. 6. Euphorbiae Pekinensis Radix and Moutan Cortex Radicis stimulated the proliferation of human lymphocytes.

• 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.

• Toxicological Research
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• v.13 no.3
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• pp.265-274
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• 1997

Uhwangchungsimwon(UC) is widely used as a herbal medicine on various circulatory disorders in Korea. The objective of this investigation was to characterize the acute, subacute hepatotoxic potency of orally administered UC in rats. In the acute and short-term studies, male rats of 150~170g were gavaged with 0, 7.5 g/kg once daily for up to 1, 5, 10 consecutive days. No differences in body weight, serum enzyme activities, absolute and relative liver weight and histopathological examination on liver between control and UC-fed groups were found. In the subacute study, UC was administered orally to both sexes of rats for 30 days(0, 1.875, 3.75 or 7.5 g/kg/day). There were no-doserelated hepatotoxic signs of general symptoms, body weight gain, water consumption and serum biochemical analysis. Slight decreases of food consumption observed at 3.75 and 7.5 g/kg groups of both sexes were due to be full of UC fed. Gross necropsy and histopathology revealed no evidence of hepatotoxicity related to UC. Our data indicate that hepatotoxicity was not caused by administration of UC up to 7.5 g/kg/dayfor 30 days in rats.

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

• Proceedings of the Korean Society of Applied Pharmacology
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• 1995.04a
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• pp.122-122
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• 1995

본 연구는 유전공학적인 방법으로 합성된 상피세포성장호르몬인 DWP-401에 대한 마우스의 반복투여에 의한 아급성독성을 조사하기 위하여 실시하였다. 시험군은 ICR 마우스 압수 각각 10 마리씩으로 하여 3 개의 처치군 및 대조군(0, 1, 0.2, 0.04 mg/kg)과 회복시험군(0, 1 mg/kg)을 두었다. 시험물질은 13 주간 경배 부 피하에 1 주에 6 회의 빈도로 투여하였고 대조군과 최고용량 군에서 5 주간의 회복기간을 두었다. 시험기간 중 체중, 사료섭취량 및 음수섭취량을 측정하였고, 뇨검사, 안검사, 혈액학적검사, 혈액생화학적 검사, 부검소견관찰, 장기중량측정 및 병리조직학적검사를 실시하였다. 이상의 실험결과 DWP-401의 마우스에 대한 표적장기는 상피세포, 간장, 비장, 부신, 방광 신장, 각 장기의 복막과 흉막, 림프계, 난소 및 투여부위였고 회복성이 인정되었다. 무해용량은 0.04 mg/kg/day였으며 확실 중독량은 0.2 mg/kg/day 이상으로 사료되었다.