• Journal of the Korean Society of Food Science and Nutrition
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• v.41 no.11
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• pp.1534-1539
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• 2012

This study was conducted to evaluate the possible subacute toxicity of gamma-irradiated Tarakjuk. Tarakjuk was irradiated at a dose of 30 kGy at room temperature. For the animal study, AIN-93G as a control diet and 30 kGy irradiated and non-irradiated Tarakjuk diets were administered to male and female ICR mice (10 mice per group) for 3 months. During the experimental period, the group fed 30 kGy irradiated Tarakjuk did not show any changes in appearance, behavior, mortality, body weight, organ weight, or food consumption compared to control. Further, all biochemical parameters were in normal ranges. In the histopathological examination of liver and kidney tissues of ICR mice, there were no significant differences between the control and 30 kGy irradiated Tarakjuk groups. These results indicate that Tarakjuk irradiated at 30 kGy did not cause any toxic effects under these experimental conditions.

• The Korea Journal of Herbology
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• v.27 no.3
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• pp.95-100
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• 2012

Objectives : This study was carried out to investigate the acute toxicity and safety of $Leejung$-$tang$($Lizhong$-$tang$) and fermented $Leejung$-$tang$($Lizhong$-$tang$) extract. Methods : To evaluate their acute toxicity and safety, 0(control group), 1250, 2500 and 5000 mg/kg of $Leejung$-$tang$($Lizhong$-$tang$) and fermented $Leejung$-$tang$($Lizhong$-$tang$) extracts were orally administered to 35 male and 35 female ICR mice. After a single administration, we observed survival rates, general toxicity, changes of body weight, and autopsy. Results : Compared with the control group, we could not find any toxic alteration in any of treated groups (1250, 2500 and 5000 mg/kg). Conclusions : $LD_{50}$ of $Leejung$-$tang$($Lizhong$-$tang$) and fermented $Leejung$-$tang$($Lizhong$-$tang$) were over 5000 mg/kg and it is very safe to ICR mice.

• Herbal Formula Science
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• v.21 no.1
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• pp.36-50
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• 2013

Objectives : To clarify the possible effect of Lycium chinese Mill (LC)., Morus alba L (MA)., and Lycium chinese Mill. +Morus alba L. (LC+MA), we have examined their influence on the development of pulmonary eosinophilic inflammation in the asthmatic murine model. Methods : Female Balb/c mice (5weeks) were immunized on two different days (21 days and 7 days before inhalational exposure) by intraperitonial injections of 0.2ml alum-precipitated Ag containing $100{\mu}g$ of OVA bound to 4 mg of aluminum hydroxide in PBS. Seven days after the second sensitization, mice were exposed to aerosolized ovalbumin for 30 minutes/day on 3 days/week for 8 weeks (at a flow rate of 250 L/min, 2.5% ovalbumin in normal saline) and, LC, MA, and LC+MA (500 mg/kg) were orally administered 3 times per a week for 8 weeks. Results : The suppressive effect of LC, MA, and LC+MA were demonstrated by the accumulation of eosinophills into airways, with the reduction of eosinophil, total lung leukocytes numbers. These were correlated with the marked reduction of IL-5, IL-13 and IL-4 levels in the BALF and serum. OVA-specific IgE levels were also decreased in serum and BAL from these mice. LC, MA, and LC+MA decreased eosinophil CCR3 expression and CD11b expression in lung cells. Conclusions : These results indicate that LC, MA, and LC+MA have high inhibitory effects on airway inflammation and hyper-responsiveness in the asthmatic murine model. The suppression of IL-5, IgE, eosinophil CCR3 expression and CD11b expression, and the increase of IFN-${\gamma}$ production in BALF seem to contribute to this effect. Hence, the results indicated that LC, MA, and LC+MA could act as a immuno-modulator which possesses anti-inflammatory and anti-asthmatic property by modulating the imbalance between Th1 and Th2 cytokines.

• The Journal of Korean Society of Virology
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• v.28 no.1
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• pp.63-69
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• 1998

To establish in vivo antiviral evaluation system by using murine herpesvirus intracerebral infection model, 5-6 female BALB/c mice per group aged 5 weeks were inoculated i.c. into cerebrum with different inocular HSV-1 F. Signs of clinical disease noted everyday for one month. Observed were body weight decrease, neurological signs and death caused by encephalitis. Mice discontinued body weight decrease were recovered from the disease, and keratitis was often observed during recovery. The groups inoculated with higher than 1,000 PFU showed 100% mortaltiy and $LD_{50}$ was <100 PFU/mouse. To study the effect of virus inoculum sizes on antiviral effect of acyclovir (ACV), mice inoculated with different inocula were administered i.p. with different doses of ACV immediately after infection, and twice a day for 5 days. The higher inculum size, the less protective. $ED_{50}$ of ACV was >25, >25, 18.4 and 8.0 mg/kg b.i.d. in the group infected with 1,000,000, 100,000, 10,000 and 1,000 PFU/mouse, respectively. $LD_{50}$ of ACV was 62.5 mg/kg b.i.d. Therapeutic index of ACV was <2.5, <2.5, 3.0 and 7.0 in the groups with inocula 1,000,000, 100,000, 10,000 and 1,000 PFU/mouse, respectively. Inoculum size 1,000 PFU/mouse showing 100% mortaltiy and 5-6 days mean time to death, 5 days drug administration and 14 days observation will be future experimental conditions.

• Toxicological Research
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• v.28 no.1
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• pp.57-65
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• 2012

In this study, the 4-week oral toxicity and anti-cancer activity of the hexane layer of Melia azedarach L. var. japonica Makino's bark extract were investigated. We carried out a hollow fiber (HF) assay and 28-day repeated toxicity study to confirm the anti-cancer effect and safety of the hexane layer. The HF assay was carried out using an A549 human adenocarcinoma cell via intraperitoneal (IP) site with or without cisplatin. In the result, the 200 mg/kg b.w of hexane layer with 4 mg/kg b.w of cisplatin treated group, showed the highest cytotoxicity aginst A549 carcinoma cells. For the 28-day repeated toxicity study, 6 groups of 10 male and female mice were given by gavage 200, 100, or 50 mg/kg b.w hexane layer with or without 4 mg/kg b.w of cisplatin against body weight, and were then sacrificed for blood and tissue sampling. The subacute oral toxicity study in mice with doses of 200, 100, and 50 mg/kg b.w hexane layer showed no significant changes in body weight gain and general behavior. The cisplatin-treated group significantly decreased in body weight compared to the control group but regained weight with 100 and 200 mg/kg b.w of hexane layer. The biochemical analysis showed significant increase in several parameters (ALT, total billirubin, AST, creatinine, and BUN) in cisplatin-treated groups. However, in the group given a co-treatment of hexane layer (200 mg/kg b.w), levels of these parameters decreased. In hematological analysis, cisplatin induced the reduction of WBCs and neutrophils but co-treatment with hexane layer (100 and 200 mg/kg b.w) improved these toxicities caused by cisplatin. The histological profile of the livers showed eosinophilic cell foci in central vein and portal triad in cisplatin treated mice. These results show that hexane layer might have an anti-cancer activity and could improve the toxicity of cisplatin.

• Reproductive and Developmental Biology
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• v.32 no.1
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• pp.45-49
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• 2008

We have previously produced transgenic (TG) mice expressing the human lactoferrin (hLF), interleukin-10 (hIL-10), and thrombopoietin (hTPO) proteins in the milk. In this study, we examined whether simple crossbreeding between two kids of a single transgenic mouse can produce double transgenics co-expressing two human proteins.. The hLF male, and the hIL-10 male were crossbred with the hIL-10 and hTPO females, and the hTPO female, respectively. PCR analysis for genotyping showed 32%, 23% and 24% double transgenic rates for hLF/hIL-10, hLF/hTPO, and hIL-10/hTPO transgenes, respectively. We analyzed the expression levels of the human proteins from double transgenic mice and compared those with their single transgenic siblings. All double transgenic co-expressed two human proteins at comparable levels to singles', unless hTPO was not co-expressed: for hLF, 1.1 mg/ml in hLF/hIL-10, whereas 0.5 mg/ml in hLF/hTPO; for hIL-10, 4.1 mg/ml in hIL-10/hLF, whereas 1.4 mg/ml in hIL-10/hTPO. Ihe downregulation of hTPO to half level of singles' was observed in double transgenic mice. The possible reason why hTPO co-expressed might lead to down-regulation of another human protein was discussed. These results suggested that double transgenic generated by crossbreeding between two singles' could be useful system for bioreactor.

• Molecular & Cellular Toxicology
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• v.2 no.3
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• pp.193-201
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• 2006

Cephalexin, one of most widely prescribed cephalosporin, has been reported to cause acute renal failure as a side effect in human and experimental animals. Although numerous animal studies have been reported for the cephalosporin nephrotoxicity, the molecular and cellular nephrotoxic mechanisms of cephalexin are still unknown. This investigation evaluated the time-dependent gene expression profile of kidney in mouse during cephalexin induced nephrotoxicity. C57BL/6 female mice were administered either saline or 1,000 mg/kg cephalexin intraperitoneally. Mice were sacrificed at 3, 6, and 24 hr after administration. Blood biochemical and histopathological results indicated cephalexin induced nephrotoxicity. Microarray experiment carried out using Affymetrix $GeneChip^{(R)}$. There were 198 informative genes that were significantly expressed >5-fold versus control at 3, 6, and 24 hr (p<0.01), of which 156 and 42 were up-and down-regulated, respectively. Major classes of up-regulated genes at 3, 6 hr included those involved in MAPK/Jak-STAT signaling pathway and immune response such as cytokine-cytokine receptor interaction and complement and coagulation cascades. At 24 hr, up-regulated genes were mainly involved in regeneration/repair and immune response; down-regulated genes were generally associated with transporters and intermediary metabolism. Among the up-regulated genes at 24 hr, several potential biomarkers on nephrotoxicity such as Kim-1, Fga, Timp1, and Slc34a2 were clustered in a same category. In addition, Tnfrsf12a and Lcn2 which were consistently up-regulated (>5 fold) were also included as potential biomarkers. These results may provide clues for elucidating the mechanism of cephalexin induced nephrotoxicity and evaluating potential biomarkers to assess nephrotoxicity.

• The Korea Journal of Herbology
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• v.26 no.4
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• pp.101-107
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• 2011

Objectives : Socheongryong-Tang (小靑龍湯, SCRT) has been widely used to treat respiratory disease. In this study, we investigate the acute toxicity and safety of fermented Socheongryong-Tang extract. Methods : To evaluate the acute toxicity and safety, 0 (control group), 1250, 2500 and 5000 mg/kg of Socheongryong-Tang and fermented Socheongryong-Tang extracts were orally administered to male and female ICR mice. After single administration, we observed survival rates, general toxicity, changes of body weight for the 14 days and autopsy. Results : Compared with the control group, we could not find any toxic alteration in all treated group (1250, 2500 and 5000 mg/kg). Conclusions : $LD_{50}$ of Socheongryong-Tang and fermented Socheongryong-Tang extracts might be over 5000 mg/kg and it is safe to ICR mice.

• Korean Journal of Veterinary Research
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• v.53 no.2
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• pp.95-101
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• 2013

The study was carried out to evaluate and compare the immune responses in mice experimentally infected with either wild-type or isogenic mutants of Salmonella enterica serovars Enteritidis (SE), Salmonella Typhimurium (ST) and Gallinarum (SG). The mutant strains were constructed by allelic replacement of some virulence-associated genes in the wild-type strains. Seven-week-old female BALB/c mice were orally or intraperitoneally inoculated by injecting bacterial suspension. To evaluate the immune responses, enzyme-linked immunosorbent assay (ELISA) and enzyme-linked immunospot (ELISPOT) assay were conducted with serum and fecal samples. As a result, the mice group infected orally with the SE mutant strain showed the highest level of specific IgA-secreting splenocytes, compared to the other groups. The peritoneally injected groups showed the greater levels of IgG1 than the orally injected groups, which was in a good agreement with the previous studies. In addition, the mutant infected groups had the similar secretion levels of antibodies with the wild-type infected groups. These results demonstrated that the SE mutant strain elicited humoral immune response as much as wild-type, implying that it can be useful as a delivery vehicle as well as a candidate of a live attenuated vaccine.

• The Journal of Korean Obstetrics and Gynecology
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• v.18 no.4
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• pp.36-53
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• 2005

Purpose : The Purpose of this research was to investigate the effects of Haingkyunghonghwatang (HKHHT) on anti-inflammatory effects. Methods : As for the parameters of inflammation, levels of several inflammatory cytokines and chemical mediators were determined in mouse lung fibroblast cells(mLFC) and RAW264.7 cells. Also, changes in pathological features by drug treatment were investigated in the in vivo edema-induced rats by carrageenin/arachidonic acid or in the colitis-induced mice by DSS treatment. Results : The cytotoxicity of HKHHT on mLFC and RAW264.7 cells wasn't observed at 100, 50, 10, and $1{\mu}g/ml$ of The treatments. $IL-1{\beta}$, IL-6 and NOS-II mRNA expression of RAW264.7 cells was inhibited by The treatments in a dose-dependent manner. HKHHT treatment of RAW264.7cells(HtRc) inhibited $TNF-{\alpha}$ and COX-2 mRNA expression. HtRc significantly inhibited IL-6 and NO production. HtRc inhibited ROS production. HKHHT inhibited rat's paw edema induced by carrageenin or arachidonate treatment in all concentrations examined. The body weight and colon length of colitis-induced mice were recovered to a normal level by DSS treatment. Clinical disease levels were significantly improved compared to the control animals. HKHHT treatment of colitis-induced mice(HtCm) significantly increased hematological values such as WBC and RBC counts, Hgb and HCT levels, but decreased PLT values. HtCm decreased IL-6 and $TNF-{\alpha}$ production significantly HtCm significantly increased CD3+(T) cell counts. In contrast, HKHHT treatment decreased CD19+ B cell counts and CD3+/CD69+ significantly, and also decreased B/T ratio (%) though not significant. Conclusion : These results indicated that HKHHT could be used for treating diverse female diseases caused by the inflammation.