• YAKHAK HOEJI
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• v.43 no.2
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• pp.180-197
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• 1999

Acute and subacute oral toxicity of $HELIKIT^{TM}$ ($^{13}C-urea$) were carried out in Sprague-Dawley rats of both sex. The toxicity of $HELIKIT^{TM}$ was compared with urea($^{12}C-urea$ which is used for control). In acute toxicity studies, we daily examined number of deaths, clinical signs, body weights and pathological examination for 14 days after single oral administration of HELIKIT or urea($^{12}C-urea$) at a dose of 5000 mg/kg. The subacute oral toxicity was investigated in Sprague-Dawley rats treated with $HELIKIT^{TM}$ at a dose of 40, 200 and 1,000 mg/kg/day or $^{12}C-urea$ at a dose of 1,000 mg/kg/day for 4 weeks. In acute toxicity studies, $HELIKIT^{TM}$ and urea did not show any toxic effect in rats and oral LD50 value was over 5,000 mg/kg rats. In subacute toxicity studies, no death occured and no drug-related changes were found in clinical observations; body weight, food consumption, opthalmoscopy. auditory test, urinalysis, hematology, blood chemistry, gross pathological examination or organ weight between $HELIKIT^{TM}$, urea and control groups. In histopathological examinations, the slight thickening of mucosa of the limiting ridge in the stomach was noted in the animals treated with $HELIKIT^{TM}$ at a dose of 1,000 mg/kg/day and also the changes in urea group at a dose of 1,000 mg/kg/day was found, but all of these changes in the changes in ures group at a dose of 1,000 mg/kg/days was found, but all of these changes in the stomach regressed after withdrawal of the test article for 2 weeks and reversibility of the effect was revealed. These results indicate that the non toxic dose level of $HELIKIT^{TM}$ was 1,000 mg/kg/day in the 4 weeks-repeated dose study, suggesting that the substitution of $^{13}C$ for carbon in urea molecule has no effect on the toxicity of urea and changes in stomach are reversible.

• Biomolecules & Therapeutics
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• v.6 no.2
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• pp.182-190
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• 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 Pharmacognosy
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• v.50 no.4
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• pp.260-271
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• 2019

This study aimed to evaluate the safety of Oplopanax elatus (Nakai) Nakai hydrothermal extract powder. It was conducted using male and female Sprague-Dawley (SD) rats. The test group was established with dose of 500 (low-dosage group), 1,000 (medium- dosage group), and 2,000 (high- dosage group) mg/day. These are investigated that number of dead animals, general symptoms, weight changes, food consumption, ophthalmological examination, urinalysis, urine volume, hematological values, plasma coagulation time values, serum biochemical values, absolute organ weight, relative organ weight and histopathological finding during the experiment. As a result of the above, toxicological changes were not observed. Therefore, the non-toxic content of Oplopanax elatus (Nakai) Nakai hydrothermal extract powder is determined to be 2,000 mg/kg/day, and target organ was not observed.

• YAKHAK HOEJI
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• v.44 no.3
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• pp.283-292
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• 2000

Angelicae gigantis Radix aqua-acupuncture solution (AGRAS) and Angelicae gigantis Radix water-extracted solution (AGRWS) were prepared and tested for their organ toxicities and chemopreventive potentials. The organ-toxicity of AGRAS to male ICR mice was studied by the measurements of glutamic oxaloacetic transaminase (GOT), glutamic pyruvate transaminase (GPT), lactate dehydrogenase (LDH) and alkaline phosphatase (ALP-s) activities after injection of AGRAS for 7 days. The activities of GOT GPT and LDH were decreased, but the activity of ALP-s was not changed with AGRAS. When AGRAS was administered once daily for 10 days before the tumor implantation, AGRAS exerted antitumor activity by inhibiting the growth of Ehrich ascites tumor cells (EATC) in viva. The inductions of quinone reductase (QR), glutathione (GSH) and glutathione S-transferase (GST) and inhibition of polyamine metabolism were tested for the chemopreventive potentials of AGRAS and AGRWS. AGRAS was potent inducer of QR activity in murine hepatoma Hepalclc7 cells. In cultured rat Ac2F cells, AGRAS was also significantly induced QR activity GSH levels were increased about 1.3 fold with AGRAS. In addition the activity of GST was increased about 2.5 fold with AGRAS at the concentration of $0.1{\;}{\times}{\;}$. The effects of AGRAS and AGRWS were tested on the growth of Acanthamoeba castellanii. Proliferation of Acanthamoeba castellanii in a broth medium was inhibited by AGRAS and AGRWS at the concentration of $1{\;}{\times}{\;}and{\;}5{\;}{\times}{\;}$, respectively: These results suggest that AGRAS has chemopreventive potential by inducing QR activity increasing GSH and GST levels and inhibition of polyamine metabolism.

• Journal of Pharmacopuncture
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• v.17 no.2
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• pp.67-72
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• 2014

Objectives: This study evaluated the single-dose toxicity of Saeng Maek San (SMS) in rats. Methods: All experiments were conducted at Biotoxtech (Chungwon, Korea), an institute authorized to perform non-clinical studies under the regulations of Good Laboratory Practice (GLP). A single-dose intravenous toxicity study was carried out on 40 6-week-old Sprague-Daley rats. The animals were randomly divided into the following four groups of ten animals each: Group 1 (G1) was the control group, with each animal receiving an intravenous injection of 1.0 mL of saline, and Groups 2, 3 and 4 (G2, G3 and G4) were the experimental groups, with the animals in the groups receiving an injection of 0.1, 0.5 and 1.0 mL of SMS, respectively. Mortality, clinical signs, body-weight changes and gross pathological findings were observed for 14 days following a single administration of SMS or saline. Organ weights, clinical chemistry and hematology were analyzed at 14 days. This study was conducted with the approval of the Institutional Animal Ethics Committee. Results: No deaths occurred in any of the four groups, indicating that the lethal dose of SMS in rats is greater than 1.0 mL/animal. Some changes in weights of male rats between the control group and the experimental groups were observed, but no significant changes in the weights of female rats were noted. To identify abnormalities in organs and tissues, we stained representative sections of each specified organ with hematoxylin and eosin for examination with a light microscope. No significant abnormalities were observed in any of the organs or tissues. Conclusion: The results suggest that intravenous injection of SMS is a safe method of treatment.

• Journal of Pharmacopuncture
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• v.17 no.2
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• pp.73-79
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• 2014

Objectives: This study was performed to analyze a 13-week repeated dose toxicity test of Sweet Bee Venom (SBV) extracted from bee venom and administered in Sprague-Dawley (SD) rats. Methods: Male and female 5-week-old SD rats were treated once daily with SBV (high-dosage group: 0.28 mg/kg; medium-dosage group: 0.14 mg/kg; or low-dosage group: 0.07 mg/kg) for 13 weeks. Normal saline was administered to the control group in a similar manner (0.2 mL/kg). We conducted clinical observations, body weight measurements, ophthalmic examinations, urinalyses, hematology and biochemistry tests, and histological observations using hematoxylin and eosin (H&E) staining to identify any abnormalities caused by the SBV treatment. Results: During this study, no mortality was observed in any of the experimental groups. Hyperemia and a movement disorder were observed around the area of in all groups that received SBV treatment, with a higher occurrence in rats treated with a higher dosage. Male rats receiving in the high-dosage group showed a significant decrease in weight during the treatment period. Compared to the control group, no significant changes in the ophthalmic parameters, the urine analyses, the complete blood cell count (CBC), and the biochemistry in the groups treated with SBV. Compared to the control group, some changes in organ weights were observed in the medium-and the high-dosage groups, but the low-dosage group showed no significant changes. Histological examination of thigh muscle indicated cell infiltration, inflammation, degeneration, and necrosis of muscle fiber, as well as fibrosis, in both the medium- and the high-dosage groups. Fatty liver change was observed in the periportal area of rats receiving medium and high dosages of SBV. No other organ abnormalities were observed. Conclusion: Our findings suggest that the No Observed Adverse Effect Level (NOAEL) of SBV is approximately 0.07 mg/kg in male and female SD rats.

• Journal of Haehwa Medicine
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• v.21 no.1
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• pp.11-21
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• 2012

New onset diabetes is a major complication after kidney transplantation. However, the natural course of posttransplantation diabetes mellitus (PTDM) remains unclear. The aim of this study was to demonstrate the detailed natural courses of PTDM according to the onset and persistency of hyperglycemia, and to investigate risk factors for development of different courses of PTDM in renal allograft recipients. The purpose of this study is to develop novel immune suppressants for PTDM using of action mechanism of them. The use of immunosuppressive drugs in transplanted patients is associated with the development of diabetes, possibly due to ${\beta}$-cell toxicity. To better understand the mechanisms leading to post-transplant diabetes, we investigated the actions of prolonged exposure of ${\beta}$-cells to therapeutical levels of tacrolimus (FK506) or cyclosporin A(CsA). The immunosuppressive drug cyclosporine(CsA) is a potent agent widely used after organ transplantations and various autoimmune disorders. After using CsA, some patients suffer severe complications including renal and vascular toxicity. The renal or vascular toxicity is influenced by the degree of the endothelial damage. FK506(tacrolimus) is a widely used immunosuppressive agent in the treatment of various medical conditions, including autoimmune disease, bone marrow and organ transplantations. We found some interesting clusters and confirmed the feasibility of cDNA microarray in the study of Immunosuppressant. In this study, we investigated gene expression patterns induced by Immunosuppressant in RIN-m5F of rat insulinoma cell line. Gene expressions evaluated using cDNA microarry in two clusters were increased or decreased. this study provides comprehensive comparison of the patterns of gene expression changes induced by CsA and FK506 in ${\beta}$-cells. This study could establish that the mode of action mechanism by which currently used insulin inhibitors inducing PTDM could be elucidated at least in part, which raises the possibility that novel immune suppressive PTDM can be developed. The molecular biological study on PTDM will also contribute the progress in diabetes research field as well as in that of PTDM.

• The Journal of Internal Korean Medicine
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• v.35 no.3
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• pp.223-243
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• 2014

Objectives: To provide information on the safety of GST (GamiSasangja-tang; CnidiiFructus, Sophora Root, Angelica Gigas Root, Clematidis Radix, Stemonae Radix, Spirodelae Herba), we carried out a 13-week repeated oral dose toxicity and a 4-week recovery test of GST in Sprague-Dawley rats. Methods: Female and male rats were treated with GST at oral doses of 1,250, 2,500, and 5000 mg/kg. The GST was administered for 13 weeks. Mortality, clinical signs, body weight changes, food consumption, ophthalmologic findings, urinalysis, hematological and biochemical parameters, gross findings, organ weights and histological markers were monitored during the study period. The rats were then monitored for 4 extra weeks to determine recovery time after the study period. Results: We found no mortality or abnormalities among clinical signs, body weight, food consumption, ophthalmologic findings, urinalysis, hematological and biochemical parameters, gross findings, organ weights or histological markers in any of the rats tested. Conclusions: The no-observed adverse effects level (NOAEL) is considered as over 5000 mg/kg for male and female rats.

• Journal of Oriental Neuropsychiatry
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• v.23 no.3
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• pp.143-160
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• 2012

Objectives : To provide information on the safety of ACM, we carried out a 13-week repeated oral dose toxicity and a 4-week recovery test of ACM in Sprague-Dawley rats. Methods : Female and male rats were treated with ACM with oral doses of 800, 2000, and 5000 mg/kg. The ACM was administered for 13 weeks. Mortality, clinical signs, body weight changes, food consumption, ophthalmologic findings, urinalysis, hematological and biochemical parameters, gross findings, organ weights and histological markers were monitored during the study period. Moreover, the rats were monitored for 4 extra weeks to determine recovery time after the study period. Results : We found no mortality and no abnormalities in clinical signs, body weight, food consumption, ophthalmologic findings, urinalysis, hematological and biochemical parameters, gross findings, organ weights and histological markers in any of the rats tested. Conclusions : The no-observed adverse effects level (NOAEL) was considered as over 5000 mg/kg for male and female rats.

• Journal of Physiology & Pathology in Korean Medicine
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• v.25 no.5
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• pp.849-856
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• 2011

This study was investigated the protective effect of Cultivated Wild Ginseng(WG) on the toxicities induced by cyclophosphamide(CP) in mice. Twenty-four male BALB/c mice were divided into non-treated normal group(n=6), CP treated control group(n=6), CP+WG treated CP+WG group(n=6), WG treated WG group(n=6). CP(100 mg/kg of b.w., i.p) was injected at 0, 7 th, 14 th, 21 th, and 28 th day of the experiment respectively. WG(4.4 g/kg, i.p.) was administrated for 35days. Body and organ(heart, liver, kidney, testis) weight were measured. Histopathological examination on the organ(heart, liver, kidney, testis), morphometric analysis, and BrdU immunohistochemistry on the testis were performed. Body weight was decreased following CP administration. In contrast, such a decrease was significantly attenuated by WG administration. CPK and AST of CP+WG group were significantly decreased compared with CP group. Histopathologically, cross sectional area of testis and diameter of seminiferous tubule were significantly increased in CP+WG group compared with CP group. BrdU labelled cells in the seminiferous tubules were remarkably decreased in CP group. Whereas the number of seminiferous tubules labelled with BrdU in spermatogonia was increased by CP+WG administration. The obtained results suggest that WG has protective effect on CP-induced toxicity. This effect might be mediated through the supplementation of vital energy.