• Toxicological Research
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• v.18 no.1
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• pp.87-98
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• 2002

This study was conducted to evaluate the safety of a recombinant human Factor VIII(GC-$\gamma$ AHF) manufactured by Korea Green Cross Company with different technology according to the Regulation of Korean Food and Drug Administration (l 998. 12. 3). In acute toxicity test, both genders of Sprague-Dawley rats and Beagle dogs were administered intravenously with GC-$\gamma$ AHF of three doses (3,125, 625 and 125 IU/kg), and single dose of 3,125 IU/kg, respectively. No dead animal and abnormal autopsy findings were found in Control and GC-$\gamma$ AHF treated group. Therefore, the 50% lethal dose ($LD_{50}$) of GC-$\gamma$ AHF was conidered to be higher than 3,125 IU/kg in rats and dogs. In the four weeks repeated intravenous toxicity study, GC-$\gamma$ AHF was administrated intravenosly to both genders of rats and dogs with 3 doses (500, 150, 50 IU/kg). There were neither dead animals nor significant changes of body weights during the experimental Period. In addition, no significant GC-$\gamma$ AHF related changes were found in clinical sign, urinalysis and other finding. Statistically changes were observed in hematological, biochemical and organ weight parameters of treated groups: however these changes were not dose dependent. No histopathological lesion were observed in both control and treated animals. Above data suggest that no observed adverse effect level of test materials in rats and dogs might be over 500 IU/kg/day in this study. In ocular irritation test, any injury on iris, conjunctiva and cornea in rabbits were not observed. The acute ocular irritation index (A.O.I.), mean ocular irritation index (M.O.I.) and Day-7 individual ocular irritation Index (I.O.I.) of GC-$\gamma$ AHF were 0. In the primary skin Irritation test, the primary irritation index (P.I.I.) oj GC-$\gamma$ AHF were 0. Therefore, the GC-$\gamma$ AHF is considered not to have the primary skin and eye toxicity in rabbits. In active systemic anaphylaxis (ASA) test, GC-$\gamma$ AHF and GC-$\gamma$ AHF emulsified with Freund's complete adjuvant (FCA) did not induce any symptom of anaphylactic shock in guinea pigs. In passive cutaneous anaphylxis (PCA) test, after sensitization with antisera of GC-$\gamma$ AHF sensitized mice, blue spots were observed on the hypodermis of back of rats, but diameter of each spot was smaller than 5 mm in each test groups except the positive control group. Based on the results of this study, GC-$\gamma$ AHF is not conidered to have any antigenic potential. In conclusion, at levels of up to 500 IU/kg, GC-$\gamma$ AHF did not produce treatment-related toxicity under the conditions of these acute-, four week repeated-toxicity, primary skin and eye toxicity, and antigenicity test.

• Journal of Life Science
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• v.30 no.3
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• pp.267-277
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• 2020

This study was conducted to assess the effect of highly concentrated onion intake on rodents. The experimental animals were divided two groups as follows; water administered group (CON) and Allium cepa administered group (ACE). The ACE group showed a slightly increases in the number of erythrocytes (RBC), hemoglobin (HGB), hematocrit (Hct) levels compared to the control group (p<0.05). Hemoglobin, monocyte, lymphocyte and neutrophil had no significant change (p>0.05) in ACE group and control group. The analysis of glutamic oxaloacetic transaminase (GOT) and glutamic pyruvic transaminase (GPT) levels showed a significant decrease in ACE group compared to the control group (p<0.05). The blood glucose, total protein, HDL-cholesterol were slightly high in ACE group, while triglyceride, total cholesterol levels were lower in ACE group compared to the control group (p<0.05). The levels of cytokines (interluekin-1α (IL-1α), interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), interleukin-10 (IL-10), interferon-γ (INF-γ), interleukin-18 (IL-18), interleukin-2 (IL-2), granulocyte-macrophage colony-stimulating factor (GM-CSF)) involved in immunity and inflammation in liver tissue and blood have all been confirmed to be within normal range. These findings could be used as basic data to show that highly concentrated dietary onion extract is not toxic to hematological indicators and immune functions.

• Toxicological Research
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• v.23 no.1
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• pp.79-86
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• 2007

The isolated plantamajoside from Plantago asiatica that is often used as a marker compound in chemotaxonomic studies has various bioactivites such as the inhibitions of cyclic AMP phosphodi-esterase and 5-lipoxygenase, microbial growth and inflammation, and currently demands the generation of toxicity data. The purpose of this study was to examine the toxicities of the single and 14 days repeated dose toxicity in Sprague-Dawley rats orally administrated with plantamajoside at dose levels of 0, 500, 1000, and 2000 mg of dried material/kg body weight/day. The results showed that there was no difference in body weight change, food intake, water consumption, or relative organ weight among different dose groups. Also we observed no death and abnormal clinical signs were observed during the experimental period. Between the groups orally administered Plantago asiatica and the control group, there was no statistical significance in hematological test or serum biochemical values. There were no gross findings at final sacrifice. There was no evidence of histopathological alteration mediated by 14 days treatment with Plantago asiatica. These results suggest that no observed adverse effect level (NOAEL) of the oral application was considered to be more than 2000 mg/kg in rats under the conditions employed in this study. Another observation was performed to investigate the safety of Plantago asiatica in respect of genotoxicity. This substance was examined that Salmonella typhimurium reversion assay (Ames test) in strain TA98, TA100, TA1535. In the reverse mutation test, Plantago asiatica did not induce mutagenicity in Samonella typhimurium with and without metabolic activation. These results indicated that Plantago asiatica had no genotoxicity.

• Journal of Applied Biological Chemistry
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• v.58 no.2
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• pp.139-143
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• 2015

In the present study, we investigated the oral toxicity of Amomum tsao-ko Crevost et Lemaire, (Zingiberaceae) extract in Balb/c mice (BALB, n=60) for 3 weeks. Balb/c mice (10 mice/group, 6 group, $20{\pm}2g$, 6 weeks) were orally administered for 21 days, with dosage of 250, 500, 1000, 2000 mg/kg/day. Ethanol extract of A. tsao-ko did not affect any significant change of mortality, clinical signs, organs and body weights. Also, there were not significantly difference from the naive group (control) in hematological and serum biochemical examination. Consequently, these findings indicate that 3-week treatment with the ethanol extract of A. tsao-ko was not any toxic effects in Balb/c mice and the no-observed adverse effect level (NOAEL) for oral toxicity was determined to be 2000 mg/kg/day under our experimental conditions.

• Asian-Australasian Journal of Animal Sciences
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• v.33 no.3
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• pp.424-435
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• 2020

Objective: The study was conducted to investigate variations in the immunophysiological responses to exercise-induced stress in Jeju and Thoroughbred horses. Methods: Blood samples were collected from the jugular veins of adult Jeju (n = 5) and Thoroughbred (n = 5) horses before and after 30 min of exercise. The hematological, biochemical, and immunological profiles of the blood samples were analyzed. Blood smears were stained and observed under a microscope. The concentration of cell-free (cf) DNA in the plasma was determined using real time polymerase chain reaction (PCR). Peripheral blood mononuclear cells (PBMCs) and polymorphonuclear cells were separated using Polymorphprep, and the expression of various stress-related and chemokine receptor genes was measured using reverse transcriptase (RT) and real-time PCR. Results: After exercise, Jeju and Thoroughbred horses displayed stress responses with significantly increased rectal temperatures, cortisol levels, and muscle catabolism-associated metabolites. Red blood cell indices were significantly higher in Thoroughbred horses than in Jeju horses after exercise. In addition, exercise-induced stress triggered the formation of neutrophil extracellular traps (NETs) and reduced platelet counts in Jeju horses but not in Thoroughbred horses. Heat shock protein 72 and heat shock protein family A (Hsp70) member 6 expression is rapidly modulated in response to exercise-induced stress in the PBMCs of Jeju horses. The expression of CXC chemokine receptor 4 in PBMCs was higher in Thoroughbred horses than in Jeju horses after exercise. Conclusion: In summary, the different immunophysiological responses of Jeju and Thoroughbred horses explain the differences in the physiological and anatomical properties of the two breeds. The physiology of Thoroughbred horses makes them suitable for racing as they are less sensitive to exercise-induced stress compared to that of Jeju horses. This study provides a basis for investigating the link between exercise-induced stresses and the physiological alteration of horses. Hence, our findings show that some of assessed parameters could be used to determine the endurance performance of horses.

• The Journal of Korean Medicine
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• v.27 no.3 s.67
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• pp.51-62
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• 2006

Objective: Although chronic non-bacterial prostatitis is a common disease, it is very difficult to treat effectively. Lygodium japonicum has traditionally been used in treatment of urinary tract inflammation and voiding disturbance. In this study, we investigated the therapeutic effects and action mechanism of Lygodium japonicum in the rat model of non-bacterial prostatitis induced by castration and testosterone treatment. Methods: Five-month-old rats were treated with $17\beta-estradiol$ after castration for induction of experimental non-bacterial prostatitis, which is similar to human chronic prostatitis in histopathological profiles. Lygodium japonicum and testosterone were administered as an experimental specimen and a positive control, respectively. The prostates were evaluated by histopathological parameters including the epithelial score and epithelio-stromal ratio for glandular damage, proliferating cell nuclear antigen (PCNA) labeling index for cyto-proliferation and a TUNEL (deoxyuridine triphosphate biotin nick end-labeling) assay for cell apoptosis. Results: While prostates of control rats revealed severe acinar gland atrophy and stromal proliferation, the rats treated with Lygodium japonicum showed a lesser range of tissue damage. Epithelial score was improved in Lygodium japonicum than that of the control (P<0.05). The epithelio-stromal ratio was lower in Lygodium japonicum when compared to that of the control (P<0.05). Although there was no difference in PCNA and TUNEL positive cells of the glandular epithelia, we found an decreased number of PCNA positive cell and concurrent increase of TUNEL positive cells in the stroma of Lygodium japonicum treated rats (P<0.01). Conclusions: These findings suggest that Lygodium japonicum may protect the glandular epithelial cells and also inhibit stromal proliferation in association with suppression of cyto-proliferation and stimulation of apoptosis. We concluded that Lygodium japonicum may be a useful remedy agent for treating the chronic non-bacterial prostatitis.

• Toxicological Research
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• v.22 no.1
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• pp.61-67
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• 2006

Changes in hematology and serum biochemistry after treatment of recombinant human erythropoietin (rHuEPO, HM10760) were screened in 4 male cynomolgus monkeys (Macaca fascicularis). Four monkeys, composed of a treatment group of HM10760 and a positive control group of $Aranesp^(R}$, were subcutaneously administered at same dose of $100{\mu}g/kg$. Both groups did not show any change in body weights and food consumption for 4 weeks compared with those of pretreatment. Both groups did not show any change in total leukocyte count (WBC) and platelet count, while both groups showed increased platelet distribution width (PDW) percentage in HM10760 group during a period from day 5 to day 59 and in $Aranesp^(R}$ group during a period from day 9 to day 26. Both groups showed increases in red blood cells (RBC), hemoglobin (HGB), and hematocrit (HCT) approximately 10 days after treatment compared with those of pretreatment (day 0). The increased levels of RBC, HGB, and HCT were much higher in HM10760 than in $Aranesp^(R}$ by the increases of $3.2%{\sim}12.5%$ for RBC, $3.8%{\sim}17.1%$ for HCT, and $1.85%{\sim}11%$ for HGB. Both groups showed increases in red cells distribution width (RDW) and reticulocyte (RET) compared with those of pretreatment, showing the highest peak from day 9. The increased level of RET lasted up to day 14 in $Aranesp^(R}$ group, while it lasted up to day 23 in HM10760 group. The increased level of RDW lasted up to day 59, it was much higher in HM10760 by the increase of $10.1%{\sim}17.6%$ than in $Aranesp^(R}$ group. In serum biochemistry, both groups showed a decrease in chloride level compared with those of pretreatment. These findings indicated that HM10760 increased RBC, HGB, HCT, RDW, and RET compared with those of pretreatment, and the increased levels were much higher in HM10760 than in $Aranesp^(R}$.

• Pediatric Gastroenterology, Hepatology & Nutrition
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• v.6 no.2
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• pp.112-119
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• 2003

Purpose: Helicobacter pylori infection is thought to be correlated with iron-deficiency anemia (IDA) at puberty. The H. pylori feoB gene, a high-affinity ferrous iron transporter, plays a central role in iron acquisition. This study aims to analyze the H. pylori feoB status according to the presence of antral gastritis with or without IDA. Methods: Fourteen H. pylori-positive patients aged from 10~18 years were categorized into subgroups based on the presence or absence of IDA. Eight patients had IDA, and the other six showed normal hematological findings. Genomic DNA was isolated from cultured H. pylori. Five sets of primers were used for PCR amplification of the feoB gene. The feoB region, 1.93 kb, was generated by linking of the PCR products and sequenced. The feoB gene sequences of H. pylori J99 and 26695 were used to compare with the clinical strains. Sequence comparisons of the feoB regions between the IDA (+) and (-) groups were performed. Results: Sequence analysis of the complete coding region of the feoB revealed 16 sites of polymorphism. Among these, 3 polymorphisms-Glu/Thr254Ala, Ile263Val, and Lys511Gln - were indigenous to Korean strains. Although statistically significant differences appear in 4 sites between IDA (+) and (-), the number of specimens are too low to assess the real differences. Conclusion: The 4 polymorphisms in the feoB gene seem to be related with IDA, but it is unclear yet because of small number of study strains. Further studies are required to prove the correlation of IDA and H. pylori infection.

• Journal of Physiology & Pathology in Korean Medicine
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• v.19 no.5
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• pp.1200-1203
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• 2005

Kami-Okchun-San(OCS) is known as an effective herbal medicine on Type 2 diabetes. We peformed to investigate acute toxicity of OCS on ICR mice. ICR mice in acute toxicity experiment were administered orally with dosages of 3,200mg/kg (low dosage group), 4,000mg/kg (middle dosage group), 5,000mg/kg (high dosage group) per single time, respectively. Body weights, clinical signs, motalities and histopathological finding were observed daily for 14 days according to the Regulation of Korean Food and Drug Administration(1999. 12. 22). Single oral administration of OCS with different dosages, no animals died of the test drug. Autopsy of animal revealed no abnormal gross findings. Therefore, LD50 value of OCS for ICR mice was more than 5,000mg/kg on oral route. Normally increasing changes were observed in body weight, drinking water and food intake in every dosage group. Hematological parameters were also observed normally in all animals. No histopathological lesions were observed in both control and treated animals. Above data suggest that no toxic dose level of OCS in ICR mice is considered to be more than 5,000mg/kg. Therefore, it was concluded that OCS have no effect on acute toxicity and side effect in ICR mice.

• Journal of Aquaculture
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• v.21 no.3
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• pp.133-138
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• 2008

We evaluated the effects of dietary supplementation of scoria on growth performances and apparent protein digestibility in juvenile parrot fish Oplegnathus fasciatus and olive flounder Paralichthys olivaceus. In experiment, parrot fish at initial average weight of $7.6{\pm}0.01g(mean{\pm}SD)$ were divided into 9 groups(three groups per dietary treatment) and fed one of three isonitrogenous diets which contained 0%, 1% and 2% of scoria, respectively. Experiment was conducted with juvenile olive flounder to demonstrate the improved apparent digestibility of protein found in the experiment. Five experimental diets were formulated to contain different levels of scoria: Diet 1(control), 0% scoria; diet 2, 1% scoria; diet 3, 2% scoria; diet 4, 3% scoria; and diet 5, 4% scoria. After 9 weeks of feeding trial(Exp), no significant differences were observed on growth performances between Scoria 2% and the control group. However, the growth was significantly lower in scoria 1% compared to that of the control group. Hematological parameters were not affected by the supplementation of scoria. Interestingly, apparent protein digestibility was improved by dietary supplementation of scoria both in parrot fish and olive flounder. The findings suggest that dietary supplementation of 2-3% scoria is optimum levels in order to improve the protein digestibility in the diets for juvenile parrot fish and olive flounder.