• Korean Journal of Veterinary Research
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• v.43 no.4
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• pp.657-666
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• 2003

The present study was undertaken to evaluate the potential adverse effects of 2-BP on pregnant dams and embryo-fetal development after maternal exposure during the gestational days (GD) 6 through 19 in Sprague-Dawley rats. The test chemical was administered subcutaneously to pregnant rats at dose levels of 0, 375, 750 and 1250 mg/kg/day. During the test period, clinical signs, mortality, body weights and food consumption were examined. All dams were subjected to caesarean section on GD 20 and their fetuses were examined for external, visceral and skeletal abnormalities. At above 750 mg/kg, toxic effects including signs of toxicity, suppressed body weight, decreased gravid uterine weight and reduced food intake were observed in pregnant dams. An increase in the fetal deaths, a decrease in the litter size, a reduction in the fetal body weight and an increase in the incidence of fetal morphological alterations were also found. There were no adverse effects on either pregnant dams or embryo-fetal development at a dose level of 375 mg/kg. These results suggest that a 14-day subcutaneous dose of 2-BP is embryolethal and teratogenic at above 750 mg/kg/day in pregnant rats. In the present experimental condition, the no-observed-adverse-effect level of 2-BP is considered to be 375 mg/kg/day for dams and embryo-fetuses, respectively.

• The Journal of Internal Korean Medicine
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• v.34 no.4
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• pp.349-361
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• 2013

Objectives : This study aimed to evaluate the single oral dose toxicity and four weeks repeated dose determination of Gamisasangja-tang (GST) in male and female Sprague-Dawley rats. Methods : In the single oral toxicity study, rats were orally administered a single dose of 0 and 5,000 mg/kg GST. There were 5 rats in each group. After single administration, mortality, clinical signs, body weight changes and gross pathological finding were observed for 14 days. In the 4-weeks repeated oral dose determination study, rats were orally administered a single dose of 0, 1,250, 2,500 or 5,000 mg/kg GST. There were 5 rats in each group. Mortality, clinical signs, body weight changes, food consumption and gross pathological finding were observed for 28 days. Organ weight, clinical chemistry and hematology were tested after 28 days. Results : There was no mortality in either of the two studies. There were also no significant differences in clinical sign, body weight, organ weights, hematological or serum chemical parameters between the GST and control groups. Conclusions : The results obtained in this study suggest that the 50% lethal dose of GST is over 5,000 mg/kg, so this finding would be expected to provide scientific evidence for the safety of GST.

• Korean Journal of Veterinary Pathology
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• v.1 no.2
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• pp.97-106
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• 1997

This study was carried out to investigate the testicular toxicity of environmental toxicant, 2-bromopropane(2-BP) recently caused occupational intoxication in Korea by light microscopy and electron microscopy. To evaluate the effect on spermatogenesis and find target germ cell 10 weeks old male Sprague-Dawley rats were treated with 5g/10m ℓ/kg/day of 2-bromopropane for 3 consecutive days orally and observed on day 1 or day 7 after treatment. 2-BP induced depletion of spermatogonia and early spermatocytes on stages I-IX or extensive degeneration of germ cells on the other stages on day 1. But extensive degeneration of germ cells without stage specificity was observed and round spermatid formed multinucleated giant cells in the lumen of seminiferous tubules on day 7. Electron microscopically Sertoli cells showed irregular shape of nucleus and cytoplasmic vauolation. And spermatocyte showed a extensive heterochromatin and cytoplasmic vacuolation. But there was no histopathological changes in the interstial cells. On the base of the results the target germ cell was spermatogonia in the early of the study but Srtoli cells also effected by high-dosed 2-BP in the late of the study.

• Korean Journal of Veterinary Research
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• v.36 no.1
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• pp.221-233
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• 1996

This experiment was carried out to study the toxic effect of solublized methylcellulose (MC). Sprague-Dawley rats were dosed with 1%(w/v) MC in 0.9% saline by gavage at a dose of 10ml/kg b.w/day or by intravenous injection at a dose of 5ml/kg b.w/day for 28 days. Clinical signs were observed once a day. Body weights, water and food consumptions were measured and urinalysis was performed several times during the experiment. Rats were sacrificed on days 3, 7, 15 and 28 for hematology, blood chemistry, organ weights and histopathology. The relative weight of the spleen and foamy cells of the spleen were increased in the gavage group. Body weight gain, food consumptions, the values of RBC, Hb, MCH, Hct, serum proteins, glucose, bilirubin, AST, and ALP were decreased in I.V. treatment group. On the other hand, water consumptions, the values of serum cholesterol, creatinine, and BUN were increased. Microscopic findings were granulomas, distended sinusoids, and hypertrophy of Kupffer cells with vacuoles in the liver. Spleen exhibited granuloma, increased extramedullary hematopoiesis, and congestion. Kidney exhibited foamy cells in the glomeruli, distension of the tubules. The findings appeared more severe when the treatment was extended. In conclusion, MC solution is not a safe vehicle for intravenous administration because of the toxic effects on the liver, kidney and spleen. In addition, a long-term and large dosage of oral administration of MC appears to be unsafe also and needs to be investigated further.

• The Korea Journal of Herbology
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• v.35 no.4
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• pp.45-50
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• 2020

Objective : This study was performed to evaluate the toxicity after a single oral administration of black raspberry extract to male and female Sprague-Dawley (SD) rats and to determine the approximate lethal dose (ALD). Methods : We previously showed that the black raspberry extract repressed the simvastatin-mediated expression of Proprotein convertase subtilisin/kexin type 9 (PCSK9) and improved Low-Density Lipoprotein cholesterol (LDL-C) uptake by hepatocytes through the induction of the Low-Density Lipoprotein Receptor expression in hepatocytes. The groups consisted of black raspberry extract groups, as an oral dose of 2,000 mg/kg and a control group. 5 weeks SD rats were randomly assigned to 4 groups of 5 rats. Each male and female SD rats were administered orally once. For 14 days after the administration, mortality, clinical signs, changes in body weight, and necropsy findings were observed according to the "Standard for Toxicity Study of Pharmaceuticals" of Korea Food and Drug Administration (KFDA) guideline and "Acute Oral Toxicity- Fixed Dose Procedure" of OECD Test Guideline. Results : There were no cases of mortality in the group administered with 2,000 mg/kg of male and female, and no abnormalities in body weight change and clinical signs. Also, no gross abnormalities were observed at the autopsy. Conclusions : As a result of a single oral administration of the black raspberry extract to SD rats, the ALD was determined to exceed 2,000 mg/kg for both male and female SD rats.

• Korean Journal of Acupuncture
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• v.39 no.2
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• pp.54-62
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• 2022

Objectives : The purpose of this study was to evaluate the potential of the test substance, SU-Eohyeol Pharmacopuncture (SUEP), to induce micronuclei in bone marrow cells of Sprague-Dawley (SD) Rats. Methods : The dose range preliminary study was performed first. 1 ml/animal was selected as the high dose of this study. Two additional lower dose levels (0.5 and 0.25 ml/animal) were produced by applying a geometric ratio of 2. In addition, the positive and negative control groups were set. Then, after intramuscular administration (1 ml/animal) of SUEP to 8-week-old male SD rats, an in vivo micronucleus test was performed to evaluate the induction of micronuclei in SD rat bone marrow cells. Results : As a result of the main study, the incidence of micronucleated polychromatic erythrocytes (MNPCE) in polychromatic erythrocytes (PCE) in the test substance SUEP groups was not statistically significantly different from the negative control group. In addition, the ratio of PCE to total erythrocytes in the test substance SUEP groups was not statistically significantly different from the negative control group. In the positive control group, the incidence of MNPCE in PCE was statistically significantly increased when compared to the negative control group. The ratio of PCE to total erythrocytes in the positive control group was not statistically significantly different from the negative control group. Conclusions : Based on these results, the test substance, SUEP, did not have any potential to induce micronuclei formation in bone marrow cells of rats under the conditions of this study.

• Anatomy and Cell Biology
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• v.56 no.4
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• pp.552-561
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• 2023

The endocrinology of type 2 diabetes (T2D) and its predisposing factors have been studied extensively while its skeletal effects have received negligible research despite this being a global disease. The cellular and molecular association between proximal humeral fractures and T2D has not been fully elucidated. We aimed to study bone cell quantities and immunolabel osteogenic and antiosteogenic cytokines. The study used 12-week-old rats (23 males) consisting of 8 Sprague Dawley (SD) and 15 Zucker Diabetic Sprague Dawley (ZDSD). Weekly mass measurements were taken while fasting blood glucose levels were recorded every 2 weeks with oral glucose tolerance tests conducted once every 4 weeks. Upon termination at the age of 28 weeks, humeri were fixed in 10% buffered formalin, prior to decalcification in ethylenediaminetetraacetic acid. The bone samples were then processed in ascending grades of alcohol using an automatic processor before embedding in paraffin wax. Sections were cut at 5 ㎛ thickness in a series for Haematoxylin and Eosin stain, and immunohistochemistry was performed with the anti-tartrate-resistant acid phosphatase (TRAP), anti-alkaline phosphatase (ALP), anti-bone morphogenetic protein 3 (BMP3), anti-transforming growth factor beta 1 (TGFβ1), anti-aged glycation end product (AGE) antibodies in the sequence. ZDSD rats had more adipocytes, BMP3 and AGEs expression with higher numbers of TRAP positive osteocytes and fewer ALP cells although no differences were found in TGFβ1 immunopositivity. We also found that T2D increases the number of AGEs immuno-positive cells, as well as its extracellular expression, thus providing a conducive environment for the interaction of the osteogenic cytokine and its antagonist to suppress osteoblastogenesis. ZDSD groups had higher adipocyte numbers therefore increased marrow adiposity in T2D.

• The Korea Journal of Herbology
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• v.39 no.2
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• pp.19-25
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• 2024

Objectives : Jeopgoltang (JGT) is a new Korean herbal medicine formulation that is used to treat bone fractures. Although JGT is frequently used in clinical practice, there is a lack of scientific evidence on its safety. This study aimed to evaluate the preclinical toxicity of JGT using a single oral dose toxicity test in Sprague-Dawley (SD) rats. Methods : Five male and female rats per group were orally administered 1,250, 2,500, or 5,000 mg/kg of JGT after fasting for 12 h. Mortality and changes in clinical signs, body weight, and necropsy findings were monitored for 14 days according to the guidelines of the Korean Ministry of Food and Drug Safety and Organisation for Economic Co-operation and Development (OECD). Results : No significant clinical signs or mortality were observed after a single administration of up to 5,000 mg/kg. In addition, no significant necropsy findings related to JGT administration were observed. Conclusions: In conclusion, these results suggest that approximate Lethal Dose (ALD) of JGT on SD rats is over 5,000 mg/kg.

• Anatomy and Cell Biology
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• v.57 no.2
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• pp.294-304
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• 2024

Type 2 diabetes mellitus is increasingly becoming more prevalent worldwide together with hospital care costs from secondary complications such as bone fractures. Femoral fracture risk is higher in diabetes. Therefore, this study aimed to assess the osteometric and microarchitecture of the femur of Zucker Diabetic Sprague-Dawley (ZDSD) femur. Ten-week-old male rats (n=38) consisting of 16 control Sprague-Dawley (SD) and 22 ZDSD rats were used. The rats were terminated at 20 weeks and others at 28 weeks of age to assess age, diabetes duration effects and its severity. Bilateral femora were taken for osteometry, bone mass measurements and micro-focus X-ray computed tomography scanning to assess the trabecular number (TbN), thickness (TbTh), spaces (TbSp), bone tissue volume to total volume (BV/TV) and volume (BV). Diabetic rats had shorter (except for 20-weeks-old), lighter, narrower, and less robust bones than SD controls that wered more robust. Although cortical area was similar in all diabatic and control rats, medullary canal area was the largest in ZDSD rats. This means that the diabetic rats bones were short, light and hollow. Diabetic rats aged 20 weeks had reduced BV, BV/TV, TbN with more spacing (TbSp). In contrast, the 28 weeks old diabetic rats only showed reduced BV and TbN. Discriminant function analysis revealed, for the first time, that osteometric parameters and TbTh, TbN, and TbSp were affected by diabetes. This knowledge is valuable in the management of diabetic complications.

• Toxicological Research
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• v.21 no.2
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• pp.129-134
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• 2005

Styrene is a commercially important chemical used mainly in the production of plastics. A toxic effect exerted by styrene exposure may cause infertility, congenital anomalies or death in offspring. Treatment with styrene for 0, 50, 100, and 500 mg/kg for 5 days in Sprague-Dawley rats significantly decreased sperm motilities and sperm counts while sperm abnormalities were significantly increased. To determine the relationship between changes in sperm motilities and roles of reactive oxygen species (ROS), we determined the effect of styrene on ROS production and mRNA expression of antioxidant enzymes in rats. ROS production was enhanced by styrene treatment in a dose-dependent manner. The mRNA expression of catalase and superoxide dismutase (SOD) 2 was strongly suppressed by styrene treatment although SOD1 or glutathione peroxidase (GPX) 4 expressions were not significantly changed. Taken together, these results indicate that styrene may cause toxic effect in rat sperm cells by enhancing oxidative stresses.