• Journal of Life Science
• /
• v.20 no.10
• /
• pp.1519-1524
• /
• 2010

Apigenin (4', 5, 7-trihydroxyflavone), a common dietary flavonoid abundantly present in fruits and vegetables, has shown remarkable anti-proliferative effects against various malignant cell lines. To observe the anti-proliferative effects, oral cavity cancer cell lines, $6{\times}10^3$ cells/well (96 well plate) of KB oral cavity tumor cells were plated and 24 hr later treated with apigenin for one day, after which MTT assay was performed. Apigenin induced cell death in a dose-dependent manner after incubation. Cell viability was significantly decreased in the group treated with 100 ${\mu}M$ apigenin for 24 hr (p<0.05) compared to the control group. To assess apoptosis, the nuclei of KB cells were stained with DAPI. The presence of chromatin condensation in the apigenin treated cells was detected on a fluorescent microscope (${\times}200$). We investigated the in vivo growth inhibitory effects of apigenin on oral cavity cancer KB tumor xenograft subcutaneously implanted in male nude mice. Apigenin was administered to mice by gavage at doses of 25 and 50 mg/kg/day in 0.2ml of PBS. Tumor volume was significantly decreased in 25 and 50 mg/kg apigenin-administration groups compared to the control group. For apoptosis analysis, TUNEL staining was performed. A significant increase in TUNEL positive cells was found in the 25 mg/kg apigenin administration group compared to the non- apigenin administration group. Histopathological changes were not observed. These results indicate that apigenin inhibits oral cavity cancer cell growth through the induction of apoptosis.

• Korean Journal of Environmental Agriculture
• /
• v.33 no.2
• /
• pp.103-110
• /
• 2014

BACKGROUND: Azadirachta indica has been widely used as environment-friendly organic materials because of its insecticidal properties. This study was carried out to investigate the acute toxicity and the subacute toxicity of Azadirachta indica extract(AIE) in rats. METHODS AND RESULTS: For the oral acute toxicity test, Sprague-Dawley rats were gavaged with 2.0 g/Kg bw of AIE. The $LD_{50}$ value was greater than 2.0 g/Kg bw for both male and female rats. For the subacute toxicity study, rats were treated with AIE at doses of 0.5, 1.0, 2.0 mg/Kg bw once a day for 4 weeks(n=10 animals per each group). There were no significant changes in body weight, food intake and water consumption observed during the experimental duration. In addition, no difference of relative kidney weight was observed among all treated groups. Serum creatinine level in the AIE 2.0 g/Kg group increased significantly compared with that of control group in male rats, but serum blood urea nitrogen was significantly decreased in a dose-dependent manner (p<0.05). Significant increase of serum cholesterol levels were observed in all AIE groups, compared with the control group, in the female rats (p<0.05). However, histopathological examination of the kidney did not reveal any significant lesions in all groups. CONCLUSION: On the basis of results, it could be concluded that oral administration AIE didn't cause any toxic response in kidney, except the increased serum cholesterol.

• Journal of the Korean Society of Food Science and Nutrition
• /
• v.42 no.8
• /
• pp.1183-1189
• /
• 2013

We investigated the effects of oyster shell extract (OSE) on papain-induced osteoarthritis in C57BL/6J mice. Osteoarthritis was induced in mice by a papain injection into the knee joint. The mice were divided into a total of five groups (n=8). The normal group was untreated, whereas the papain group (negative control) was induced with osteoarthritis and treated with water daily. The papain+DS group (positive control) was treated with diclofenac sodium. Papain+OSE groups were treated with OSE concentrations of 100 and 200 mg/kg/bw for 20 days. Proteoglycan content in articular cartilage was analyzed through safranine-O fast green staining and H&E staining. The histopathological changes in cartilage were measured by the Rudolphi score approach. The contents of tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$), interleukin (IL)-$1{\beta}$, and IL-6 in plasma were analyzed by the ELISA method. After experiments, body weights of the treated groups were not significantly different compared with the normal group. Cartilage loss and joint instability significantly improved in a dose-dependent manner in the OSE-treated group compared with the papain group (P<0.05). Proteoglycan content was significantly higher in the OSE-treated group than the papain group (P<0.05). Osteoarthritis scores of the OSE-treated group were significantly decreased compared with the papain group (P<0.05). TNF-${\alpha}$, IL-$1{\beta}$, and IL-6 content in the plasma of the papain+OSE treated groups significantly decreased in a dose-dependent manner compared with the papain group (P<0.05). These results suggest that OSE treatment might have anti-arthritic effects on papain-induced osteoarthritis in C57BL/6J mice.

• Clinical and Experimental Pediatrics
• /
• v.48 no.12
• /
• pp.1378-1384
• /
• 2005

Purpose : We hypothesized dexrazoxane(DXR) and pentoxifylline(PTX) may prevent myocardial damage in adriamycin(ADR)-induced cardiomyopathic rat model. We also investigated their effects on the myocardial apoptosis and fibrosis in ADR induced cardiomyopathy. Methods : The six-week old female Spregue-Dawley rats were divided into control group(CNT, n=4), ADR group(n=6), ADR+DXR group(DXR, n=5), ADR+PTX group(PTX, n=6), ADR+DXR+PTX group(DXPT, n=5). ADR(5 mg/week, twice) was administrated intravenously to rats except CNT group to induce cardiomyopathy. The PTX(50 mg/kg/day) was administered daily from day-0 to Day-21. The DXR(100 mg/kg) was administered 30 minutes before each ADR injection. On day 21, the rats were sacrificed and the degree of histopathologic changes of hypercontraction band necrosis, cytoplasmic vacuolar change and fibrosis were scored. Immunohistochemical staining for Bcl-2 expression and RT-PCR for $TNF-{\alpha}$ and CTGF were performed. Results : Histopathological scores of myocardial damage were significantly higher in ADR rats than CNT rats(P<0.05), and significantly lower in DXPT rats than ADR rats(P<0.01). Myocardial fibrosis was prevented in both PTX rats and DXPT rats. The expression of Bcl-2 was weaker in ADR rats than that in CNT rats(P<0.05), and stronger in both DXR and DXPT rats than that in ADR rats (P<0.05). $TNF-{\alpha}$ concentration of ADR rats was not different from that of treated groups. Conclusion : DXR prevented myocyte apoptosis with increased Bcl-2 expression, and PTX prevented myocardial fibrosis in ADR induced cardiomyopathic rats. The combination therapy of DXR and PTX showed prevention of cardiomyopathy in ADR induced cardiomyopathy rat model.

• Journal of Preventive Medicine and Public Health
• /
• v.27 no.1 s.45
• /
• pp.11-24
• /
• 1994

The studies reported here were undertaken to investigate the effects of mercury chloride on immune system of Balb/c mouse employing a flexible tier of in vitro and in vivo assays. Mercury chloride inhibited the proliferative responses of spleen cells to lipopolysaccharide, pokeweed mitogen, and phytohemagglutinin as a dose-dependent manner. This inhibitory effect was observed not only when $HgCl_2$ was added 2nd or 3rd day of 3 days culture period but also when spleen cells was pretreated with $HgCl_2$ for 2 hours. Mercury chloride, however, potentiated the production of IgM and IgG from spleen cells. During the $HgCl_2$ administration by drinking for 3 weeks, the weight gain of mice was significantly blunted than that o control group mice, while no overt signs related to mercury toxicity were noted in any mice of experimental group. There was no change in thymus and spleen weights, and in histological findings of kidney, bone marrow of femur, thymus, spleen, and popliteal lymph node after 3 weeks of mercury exposure. However, $HgCl_2$ induced a significant increase of total serum IgM, IgG including $IgG_1,\;IgG_{2a}\;and\;IgG_{2b}$, and IgE in Balb/c mice. Treatment in vivo with anti-IL-4 monoclonal antibody significantly abrogated the $HgCl_2$-induced increase in total serum IgG1 and IgE. Whereas $HgCl_2$ potentiated total serum IgM and IgG, there was no difference in total serum hemagglutinin to SRBC (Sheep Red Blood Cell) between experimental and control group mice when these mice were immunized with SRBC. All these findings observed in Balb/c mice suggest that mercury perturbates well-orchestrated regulation of immune responses before developing histopathological changes in lymphoid tissues.

• Journal of Life Science
• /
• v.16 no.5
• /
• pp.780-787
• /
• 2006

Asthma is a chronic inflammatory disorder of the airways, which characterized by bronchial hyperresponsiveness, reversible airflow limitation and respiratory symptoms. Internationally, the prevalence of asthma has been increased over last 3 decades. Recently, several studies of asthma have been reported with gradually increasing importance. To tesify the hypothesis that interleukin (IL)-4 and IL-10 may be an important determinant of the severity of airway inflammation, their expression was studied in mouse model of asthma. BALB/c mouse, IL-4 Knockout (KO) mouse and IL-10 KO mouse were sensitized with intraperitoneal injection of ovalbumin adsorbed to aluminum potassium sulfate, followed by challenges with intranasal ovalbumin on 3 consecutive days. The severity of pulmonary inflammation was assessed by eosinophilia in BAL fluid, number of total BAL cells, histopathological changes in lung tissues, and immunohistochemical staining against IL-4 and IL-10. In BAL fluid, the number of total cells was significantly increased in asthma induced mouse compare to the control. In asthma induced mouse, eosinophil was increased to 56% and neutrophil was 0.2%. In H &E stains, eosinophilic infiltration and epithelium hyperplasia were clearly noticed in asthma induced mouse. In immunohistochemical staining for IL-4 and IL-10, there was no positive reaction in control group. However, very strong reactions were appeared in asthma induced group. In this research, IL-4 and IL-10, which seem to play a central role in allergic asthma, KO mouse was utilized to test the causative relationship between airway inflammation and role of specific cytokine. Asthma induced IL-4 and IL-10 KO mice showed much decreased inflammatory reactions in the number of total BAL cells, in eosinophilic infiltration, and in immunohistochemical stains against diverse inflammatory proteins. These results suggest that IL-4 and IL-10 increase the asthmatic reactions in vivo mice model.

• The Korean Journal of Food And Nutrition
• /
• v.26 no.1
• /
• pp.66-77
• /
• 2013

In this study, we investigated the preventive effects of the mulberry leaf tea fermented by Monascus pilosus on high fat-induced obesity, hyperlipidemia, and fatty liver in mice. Non-fermented mulberry leaf tea powder (UM) and fermented mulberry leaf tea powder (FM) were supplemented with high-fat diet at 2% (wt/wt) dosage for 8 weeks. Both UM and FM lowered body weight gain, feed efficiency ratio, epididymal fat, serum triglyceride, total cholesterol and LDL-cholesterol increased markedly with high fat diet (HC) in mice. FM showed more significant effects when it was compared with UM. In addition, Hepatic lipid peroxides and xanthin oxidase activities of the UM and FM were significantly lower than those of HC, despite the lack of a big difference in the amount of hepatic GSH. Activities of ROS scavenging enzymes and serum alanine aminotransferase activity were also examined as a parameter of hepatic damage. The UM and FM groups showed a recovery to NC group from significant changes induced by HC. Finally, histopathological analyses of liver samples revealed a decrease of lipid accumulation in hepatocytes in the UM and FM groups. These results suggest that UM and especially FM can reduce the development of obesity, hyperlipidemia and fatty liver.

• Journal of Chest Surgery
• /
• v.36 no.5
• /
• pp.356-362
• /
• 2003

Background: Intralobar and extralobar pulmonary sequestrations have been considered as congenital lesions that occur at different stages of embryonic life. However, most cases of intralobar pulmonary sequestration (IPS) seem to have an acquired origin, as they are absent in infants and associated anomalies are relatively, uncommon among them. Material and Method: The cases of 25 patients who were diagnosed as IPS after surgical resection from December, 1985 to July, 2002 were included in this study. The medical records wire retrospectively reviewed and the clinical characteristics were age at operation; gender; symptoms at presentation; presence of congenital anomalies; combined diseases; preoperative studies and diagnosis; location of the lesion; method of surgical resection; origin, size and numbers of aberrant artery; histopathological findings; and postoperative complications. Result: There were 17 (68%) female patients and 8 (32%) male patients, their ages ranged from 1 to 57 and mean value was 23 years old. Though 14 patients (56%) complained of respiratory symptoms such as pneumonia and recurrent respiratory infections, a large number of patients (44%) were asymptomatic or had chest pain only when the lesion was discovered. Only 8 patients (32%) were diagnosed as pulmonary sequestration preoperatively and 8 (32%) were suspected as mediastinal or lung tumor, 5 (20%) were congenital or acquired cystic lung disease, and 4 (16%) were lung abscess or bronchiectasis, respectively. The majority of aberrant arteries (86.4%) confirmed during the operation were originated from thoracic aorta and 2 were thoracic and abdominal aorta, 1 was abdominal aorta, respectively. The younger patients (less than 10 years old) had more other congenital anomalies (30% vs 6.7%) but the proportion of congenital IPS was not significantly different (10% vs 6.7%, p>0.05) compared with elder patients. Histopathologically, almost all lesions showed chronic inflammation, cystic changes and similar pleural adhesions regardless of age. Conclusion: The large portion of the patients with IPS (44%) was clinically asymptomatic or presented non-respiratory symptoms at diagnosis and likely to be diagnosed as mediastinal or lung tumor especially in elder patients. Though the younger patients had more other congenital anomalies, most cases of IPS proved to be acquired lesions in terms of the histopathlogical findings and the proportion of congenital evidences.

• Korean Journal of Environmental Biology
• /
• v.32 no.3
• /
• pp.216-224
• /
• 2014

Decrease in dissolved oxygen concentrations associated with temperature fluctuation is an important criteria to evaluate the mortality rate of the species. Based on this parameter, we investigated the survival rate, physiological response and histological change of warty sea squirt. It was found that the survival rate of the warty sea squirt species was 63.3% at $23^{\circ}C$ and 56.6% at $26^{\circ}C$ respectively. However, exposure of six days at $29^{\circ}C$ caused deaths among species, which indicated the 6day-$LT^{50}$ of the tested species to be $24.58^{\circ}C$ ($19.48{\sim}35.48^{\circ}C$). Further, after 11 day of exposure, the dissolved oxygen concentration has been found to decrease, with the survival rate of 20% at $4.0mg\;L^{-1}$ and deaths at $2.0mg\;L^{-1}$, thus 11day-$LC^{50}$ calculated to be $3.88mg\;L^{-1}$ ($3.29{\sim}4.57mg\;L^{-1}$). In addition, decrease in rate of oxygen consumption and excretion of ammonia was also noted at this critical water temperature and dissolve doxygen concentration. Moreover, there has been common histopathological changes were observed in warty sea squirt's gill pouch, digestive tract, and tunic as follows such as: proliferation of epithelial cells, condensation and necrosis, permeation of phagocyte and blood cell, loss of cilium and muscular fiber degeneration. Based on our study results, we suggest that these parameters can also be useful to evaluate the survival rate and physiological response in other species.

• Journal of the Korean Society of Food Science and Nutrition
• /
• v.43 no.1
• /
• pp.47-54
• /
• 2014

The aim of this study is to evaluate the effects of green tea polyphenol (GTP) on anticancer treatment with cisplatin (CP), using both an in vitro cell culture model and an in vivo mouse model of established breast tumor. Mouse breast cancer cells (EMT6) were treated with or without GTP and CP followed by determination of the cell viability using an MTT assay. The relative cell viability of CP treated EMT6 cells was 96% at a 20 ${\mu}g/mL$ concentration of cisplatin; however, in combination with GTP (50 ${\mu}g/mL$), the cell viability decreased to 20% at the same concentration of CP (20 ${\mu}g/mL$). For the in vivo study, EMT6 cells were inoculated into Balb/c mice for the establishment of a tumor-bearing mice model. The tumor-bearing mice were treated with CP (5 mg/kg. i.p.) with or without dietary GTP (0.2% drinking water). Tumor growth was monitored by a measurement of tumor size using a digital caliper, and nephrotoxicity was determined by enzymatic and histological examinations. The levels of p53 and caspase-3 in tumor tissues were examined by a Western blot. In tumor-bearing mice treated with GTP plus CP, the increment of tumor volume showed a significant reduction, compared with CP or GTP alone. The levels of p53 and cleaved caspase-3 (caspase-3/p17) in tumor tissues of tumor-bearing mice were increased by CP and GTP compared to CP alone. In CP treated tumor-bearing mice, ${\gamma}$-glutamyltranspeptidase (GGT) and alkaline phosphatase (AP) activities were decreased, and marked tubular necrosis and dilatation were observed in the kidney. CP-induced enzymatic and histopathological changes in the kidney of tumor-bearing mice were reduced by combinations of GTP with CP. The results of these experiments demonstrated that dietary GTP has a potentiating effect on CP anti-tumor activity and a protective effect against CP-induced renal dysfunction. Therefore, GTP may be used as a modulator in anticancer treatment with CP.