• Title/Summary/Keyword: ANIMAL MODEL

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Chronic Alcohol Consumption Results in Greater Damage to the Pancreas Than to the Liver in the Rats

  • Lee, Seong-Su;Hong, Oak-Kee;Ju, Anes;Kim, Myung-Jun;Kim, Bong-Jo;Kim, Sung-Rae;Kim, Won-Ho;Cho, Nam-Han;Kang, Moo-Il;Kang, Sung-Koo;Kim, Dai-Jin;Yoo, Soon-Jib
    • The Korean Journal of Physiology and Pharmacology
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    • v.19 no.4
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    • pp.309-318
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    • 2015
  • Alcohol consumption increases the risk of type 2 diabetes. However, its effects on prediabetes or early diabetes have not been studied. We investigated endoplasmic reticulum (ER) stress in the pancreas and liver resulting from chronic alcohol consumption in the prediabetes and early stages of diabetes. We separated Otsuka Long-Evans Tokushima Fatty (OLETF) rats, a type-2 diabetic animal model, into two groups based on diabetic stage: prediabetes and early diabetes were defined as occurrence between the ages of 11 to 16 weeks and 17 to 22 weeks, respectively. The experimental group received an ethanol-containing liquid diet for 6 weeks. An intraperitoneal glucose tolerance test was conducted after 16 and 22 weeks for the prediabetic and early diabetes groups, respectively. There were no significant differences in body weight between the control and ethanol groups. Fasting and 120-min glucose levels were lower and higher, respectively, in the ethanol group than in the control group. In prediabetes rats, alcohol induced significant expression of ER stress markers in the pancreas; however, alcohol did not affect the liver. In early diabetes rats, alcohol significantly increased most ER stress-marker levels in both the pancreas and liver. These results indicate that chronic alcohol consumption increased the risk of diabetes in prediabetic and early diabetic OLETF rats; the pancreas was more susceptible to damage than was the liver in the early diabetic stages, and the adaptive and proapoptotic pathway of ER stress may play key roles in the development and progression of diabetes affected by chronic alcohol ingestion.

Anti-inflammatory Effects of Flavonoids on TNBS-induced Colitis of Rats

  • Joo, Minjae;Kim, Han Sang;Kwon, Tae Hoon;Palikhe, Alisha;Zaw, Tin Sandar;Jeong, Ji Hoon;Sohn, Uy Dong
    • The Korean Journal of Physiology and Pharmacology
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    • v.19 no.1
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    • pp.43-50
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    • 2015
  • It has been shown that the extracts including eupatilin and quercetin-3-${\beta}$-D-glucuronopyranoside had mucoprotective effects on the esophagus and stomach through their antioxidant activities. This study was designed to investigate the anti-inflammatory effect of these flavonoid compounds in an animal model of inflammatory bowel disease induced by 2,4,6-trinitrobenzene sulfonic acid. Experimental colitis was induced by intracolonic administration of 2,4,6-trinitrobenzene sulfonic acid. Extracts including eupatilin or quercetin-3-${\beta}$-D-glucuronopyranoside were orally administered to animals 48, 24, and 1 h prior to the induction of colitis and then again 24 h later. The animals were sacrificed 48 h after by 2,4,6-trinitrobenzene sulfonic acid treatment and the macroscopic appearance of the colonic lesions was scored in a blinded manner on a scale of 1 to 10. The inflammatory response to colitis induction was assessed by measuring myeloperoxidase activity, nitric oxide production, tumor necrosis factor-${\alpha}$ expression, total glutathione levels, and malondialdehyde concentrations in the colon. The results indicated that extracts including eupatilin and extracts including quercetin-3-${\beta}$-D-glucuronopyranoside dose-dependently improved the morphology of the lesions induced by 2,4,6-trinitrobenzene sulfonic acid and reduced the ulcer index accordingly. In addition, rats receiving extracts including eupatilin and extracts including quercetin-3-${\beta}$-D-glucuronopyranoside showed significantly decreased levels of mucosal myeloperoxidase activity, nitric oxide production, tumor necrosis factor-${\alpha}$ expression, and malondialdehyde levels, and increased total glutathione levels. Extracts including eupatilin and extracts including quercetin-3-${\beta}$-D-glucuronopyranoside ameliorated the inflammatory response and colonic injury in acute colitis by decreasing oxidative stress and neutrophil activation. Extracts including eupatilin and extracts including quercetin-3-${\beta}$-D-glucuronopyranoside may inhibit acute colitis.

Evaluation of Diagnostic Performance of a Polymerase Chain Reaction for Detection of Canine Dirofilaria immitis (개 심장사상충을 진단하기 위한 중합연쇄반응검사 (PCR)의 진단적 특성 평가)

  • Pak, Son-Il;Kim, Doo
    • Journal of Veterinary Clinics
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    • v.24 no.2
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    • pp.77-81
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    • 2007
  • Diagnostic performance of polymerase chain reaction (PCR) for detecting Dirofilaria immitis in dogs was evaluated when no gold standard test was employed. An enzyme-linked immunosorbent assay test kit (SnapTM, IDEXX, USA) with unknown parameters was also employed. The sensitivity and specificity of the PCR from two-population model were estimated by using both maximum likelihood using expectation-maximization (EM) algorithm and Bayesian method, assuming conditional independence between the two tests. A total of 266 samples, 133 samples in each trial, were randomly retrieved from the heartworm database records during the year 2002-2004 in a university animal hospital. These data originated from the test results of military dogs which were brought for routine medical check-up or testing for heartworm infection. When combined 2 trials, sensitivity and specificity of the PCR was 96.4-96.7% and 97.6-98.8% in EM and 94.4-94.8% and 97.1-98% in Bayesian. There were no statistical differences between estimates. This finding indicates that the PCR assay could be useful screening tool for detecting heartworm antigen in dogs. This study was provided further evidences that Bayesian approach is an alternative approach to draw better inference about the performance of a new diagnostic test in case when either gold test is not available.

Comparative evaluation to select optimal adjuvant of novel type Salmonella Typhimurium inactivated bacteria for protecting Salmonella infections in a murine model (마우스에서 살모넬라 감염증 예방을 위한 신개념 Salmonella Typhimurium 불활화 사균체에 최적 adjuvant 선택을 위한 효능 비교 시험)

  • Moon, Ja-Young;Ochirkhuyag, Enkhsaikhan;Kim, Won-Kyong;Lee, Jun-Woo;Jo, Young-Gyu;Kwak, Kil Han;Park, Byung Yong;Hur, Jin
    • Korean Journal of Veterinary Service
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    • v.43 no.2
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    • pp.89-97
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    • 2020
  • This study was carried out to examine a novel inactivated Salmonella Typhimurium (S. Typhimurium) vaccine candidate for protection of mice against salmonellosis by immunization of BALB/c mice using various type adjuvant. The novel type-inactivated vaccine candidate was constructed by adding Chlorhexidine digluconate solution. BALB/c mice were divided into 6 groups of 15 mice apiece. The mice were intramuscularly (IM) primed at 6 weeks of age and were IM boosted 8 weeks of age. Groups A and B mice were injected with sterile phosphate-buffered saline as controls; group C mice were inoculated with 5×108 cells/100 µL of formalin-inactivated S. Typhimurium cells and adjuvant ISA70; groups D~F mice were immunized with 5×108 cells/100 µL of the inactivated vaccine candidate and adjuvant ISA70, adjuvant IMS1313 and adjuvant IMS1313 containing 30 ㎍/mL of GI24, respectively. All mice (except group A mice) were orally challenged with a virulent S. Typhimurium strain at 10 weeks of age. Mice from groups C-F had significantly increased IgG levels compared to control groups (A-B) mice. The levels of splenocyte IFN-γ and IL-4 in mice of all groups were measured by ELISA, resulting in increased immunity in group F mice compared to those of groups A-E mice. These data suggested that systemic and cell-mediated immune responses were highly induced by IM immunization with the vaccine candidate and adjuvant IMS1313 containing GI24. Furthermore, clinical signs such as death were observed in only 20% of group F mice after virulent Salmonella strain challenge, however, groups B and C (100%), and groups D and E (60%) mice died. This data suggested that mice immunized by intramuscular prime and booster with this vaccine candidate and adjuvant IMS1313 containing GI24 effectively protected mice from salmonellosis.

Overexpression of Galectin-3 in Macrophages of C57BL/6 mice with Experimental Autoimmune Encephalomyelitis (자가면역성 뇌척수염을 유도한 C57BL/6 마우스 큰포식세포에서의 Galectin-3의 과발현)

  • Kim, Dae Seung;Hwang, Insun;Park, Suk-jae;Ahn, Ginnae;Park, Sang-Joon;Park, Hyun Jeong;Joo, Hong-Gu;Jee, Youngheun
    • Korean Journal of Veterinary Research
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    • v.51 no.2
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    • pp.139-149
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    • 2011
  • Experimental autoimmune encephalomyelitis (EAE) is an inflammatory disease in the murine central nervous system (CNS) and has long been used as an animal model for human multiple sclerosis. Development of EAE requires coordinated expression of a number of genes that are involved in the activation and effector functions of inflammatory cells. Galectin-3 (Gal-3) is a member of the betagalactoside- binding lectin family and plays an important role in inflammatory responses through its functions on cell activation, cell migration or inhibition of apoptosis. We investigated the functional role of Gal-3 in EAE mice following immunization with myelin oligodendrocyte glycoprotein $(MOG)_{35-55}$ peptide. During the peak stage of EAE, the localization of Gal-3 in inflammatory cells markedly increased in subarachnoid membranes and perivascular regions of CNS. In contrast, Gal-3 was weakly detected in cerebrum and spinal of the recovery stage of EAE. Consistent with this finding, western blot analysis revealed that Gal-3 expression was significantly increased at the peak stage while it was slightly decreased at the recovery stage in the CNS. In addition, the population of $CD11b^{+}$ macrophage expressing Gal- 3 in spleen of EAE mice was markedly increased compared with control mice. In fact, most of activated macrophages isolated from spleen of EAE mice expressed Gal-3. Taken together, our results demonstrate that the over-expression of Gal-3 in activated macrophages may play a key role in promoting inflammatory cells in the CNS during EAE.

Inhibitory Effect of Cynaroside Isolated from Lonicera japonia Thunb on Doxorubicin-induced Necrosis in Human Renal Proximal Tubular HK-2 Cells (인동덩굴로부터 분리된 Cynaroside이 Doxorubicin으로 유도된 인간 근위세뇨관 HK-2 세포의 괴사에 미치는 저해 효과)

  • Nho, Jong Hyun;Jung, Ho Kyung;Lee, Mu Jin;Jang, Ji Hun;Sim, Mi Ok;Jung, Ja Kyun;Jung, Da Eun;An, Byeong Kwan;Cho, Hyun Woo
    • Korean Journal of Medicinal Crop Science
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    • v.25 no.5
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    • pp.322-327
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    • 2017
  • Background: Cynaroside is a flavone, a flavonoid-like compound, known by different names (luteoloside and cinaroside). It is commonly found in Lonicera japonica Thunb., Chrysanthemum moriflium, and Angelica keiskei. The process of cell death has been classified as necrosis and apoptosis. Necrosis refers to unregulated cell death induced by a chemotherapeutic agent. Doxorubicin is an anthracycline anti-cancer drug used to treat acute leukemia, cancer, and lymphoma. However, it induces nephrotoxicity including tubular damage. Therefore, we investigated the protective effect of cynaroside against doxorubicin-induced necrosis in HK-2 cells. Methods and Results: To confirm the beneficial effect of cynaroside on doxorubicin-induced necrosis, HK-2 cells, a human proximal tubule epithelial cell line were treated with $10{\mu}M$ doxorubicin and $80{\mu}M$ cynaroside. Doxorubicin treatment resulted in increased DNA fragmentation, caspase-3 activity and mitochondria hyperactivation during cell necrosis. However, pretreatment with $80{\mu}M$ cynaroside attenuated DNA fragmentation, caspase-3 activity and mitochondria hyperactivation induced by $10{\mu}M$ doxorubicin in HK-2 cells. Conclusions: These results indicated that pretreatment with cynaroside ameliorated doxorubicin-induced necrosis in HK-2 cells. Therefore, cynaroside be used as a therapeutic agent for improving doxorubicin-induced nephrotoxicity. However, further studies are required to evaluated the toxicity of cynaroside treatment in animals and to determine its protective effect against doxorubicin-induced nephrotoxicity in an animal model.

Improvement Effect of Non-alcoholic Fatty Liver Disease by Curcuma longa L. Extract (강황 추출물의 비알코올성 지방간 질환 개선 효과)

  • Lee, Young Seob;Lee, Dae Young;Kwon, Dong Yeul;Kang, Ok Hwa
    • Korean Journal of Medicinal Crop Science
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    • v.28 no.4
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    • pp.276-286
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    • 2020
  • Background: Non-alcoholic fatty liver disease (NAFLD) is a chronic liver disease associated with multiple metabolic disorders. The medicinal plant Curcuma longa L. is widely distributed in Asia and has been used to treat a spectrum diseases in clinical practice. To date, there are inadequate reports of the effects of C. longa 50% EtOH extract (CE) on NAFLD. Therefore, in this study, we evaluate the CE on an NAFLD animal and elucidate the mechanism of action. Methods and Results: C57BL/6J mice fed a methionine-choline deficient diet (MCD) were treated with CE or milk thistle, and changes in inflammation and stetosis were assessed. Experimental animals were divided into six group (n = 10); Normal, MCD, MCD + CE 50 mg/kg/day (CE 50), MCD + CE 100 mg/kg/day (CE 100), MCD + CE 150 mg/kg/day (CE 150), and the Control, MCD + Milk thistle 150 mg/kg/day (MT 150). Body weight, liver weight, liver function, and histological changes were assessed in experimental animals. Quantitative real-time polymerase chain reaction and western blot analyses were performed on samples collected after 4 weeks of treatment. We observed that CE administration improved MCD-diet-induced lipid accumulation, and triglyceride (TG) and total cholesterol (TC) levels in serum. Treatment with CE also decreased hepatic lipogenesis through modulation of the sterol regulatory element binding protein-1 (SREBP-1), CCAAT-enhancer binding protein α (C/EBPα), fatty acid synthase (FAS), and peroxisome proliferator-activated receptor γ (PPARγ) expresion. In addition, the use of CE increased adenosine monophosphate-activated protein kinase (AMPK) phosphorylation and inhibited the up-regulation of toll-like receptor (TLR)-2 and TLR-4 signaling and the production of inflammatory mediators. Conclusions: In this report, we observed that CE regulated lipid accumulation in an MCD dietinduced NAFLD model by decreasing lipogenesis. These data suggeste that CE could effectively protect mice against MCD-induced NAFLD, by inhibiting the TLR-2 and TLR-4 signaling cascades.

Inhibitory Effects of Portulaca Oleracea Ethanol Extract and Glechoma Hederacea Ethanol Extract on the Periodontitis (치주염증에 대한 마치현 및 금전초 에탄올 추출물의 억제 효과)

  • Park, Young Mi;Lee, Young-Rae;Park, Sang Hoon;Lee, Bong Gun;Park, Yeon Ju;Oh, Hong Geun;Moon, Dae In;Son, Min Woo;Kang, Yang Gyu;Kim, Ok Jin;Lee, Seok-Ryun;Lee, Choong Hun;Kim, Min Seuk;Lee, Hak Yong
    • Journal of Physiology & Pathology in Korean Medicine
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    • v.29 no.1
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    • pp.46-50
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    • 2015
  • Both Portulaca oleracea (PO) and Glechoma hederacea (GH) have been used as traditional medicine due to the multiple pharmacological activities. However, the effects of PO and GH in the pathology of periodontitis is still elusive. In this study, we examined anti-microbial activity of PO ethanol extract (POEE) and GH ethanol extract (GHEE) in vitro, and physiological effects of POEE and GHEE on the cell inflammatory responses and the severity of periodontitis were determined using the rat periodontitis model. Our results indicate that POEE and GHEE had no effects on the proliferation of streptococcus mutans and on LPS-mediated inflammatory responses in gingival fibroblast cells. Notably, ingestion of POEE and GHEE resulted in attenuating the severity of periodontitis and population change of immune cells. These data suggests that PO and GH should be considered as candidates for relieving the severity of periondontitis.

Induction of Apoptosis by Methanol Extract of Gloiopeltis furcata in Human Leukemia Cell Line U937 (인체백혈병세포의 증식에 미치는 불등가사리 메탄올 추출물의 영향)

  • Choi, Woo Young;Park, Cheol;Kim, Gi Young;Lee, Won Ho;Bae, Song-Ja;Choi, Yung Hyun
    • Journal of Marine Bioscience and Biotechnology
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    • v.1 no.2
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    • pp.76-83
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    • 2006
  • Epidemiological studies have indicated that the ubiquitous consumption of seaweeds is a protective factor against some types of cancer. Previous results showed that the administration of seaweed powder or extract reduced the incidence rate of chemically induced tumorigenesis using in vivo animal model. Recently, we reported that the extracts of Gloiopeltis furcata, a kind of Korean edible seaweed, caused he cell growth inhibition of various human cancer cell lines, among them methanol extract exhibited a relatively strong antiproliferative activity. However, the molecular mechanisms of this seaweed in malignant cells have been poorly studied until now. To elucidate this problem, we investigated the effects of methanol extract of G. furcata (MEGF) on the growth inhibition in several human cancer cell lines, and further we analyzed the effects of this extract were tested on the activity of apoptosis induction in human leukemic cells. The results demonstrated that MEGF treatment resulted in the morphological changes and the growth inhibition in a dose-dependent manner. Furthermore, MEGF potently suppresses the growth of human leukemic U937 cells by induction of apoptosis, which was associated with induction of cyclin-dependent kinase inhibitor p21(WAF1/CIP1) in a tumor suppressor p53-independent fashion and up-regulation of Fas/FasL system. Further studies will be needed to identify the active compounds that confer the anticancer activity of MEGF. Once such compounds are identified, the mechanisms by which they exert their effects can begin to be characterized.

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Effect of Wild Plant Extracts Based on Korea Traditional Prescription on Endurance Exercise Performance during Calorie Restriction Period (초저열량식이로 인한 체력 저하에서 산야초추출물의 지구력 증진 효과)

  • Kim, Joong-Hark;Kim, Hwa-Young;Chang, Hey-Eun;Chung, Ji-Sang;Hwang, Sung-Joo;Park, Mi-Hyoun;Hong, Seong-Gil
    • Korean Journal of Food Science and Technology
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    • v.38 no.1
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    • pp.147-151
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    • 2006
  • Effects of wild plant extract (Lak) based on Korea traditional prescription on maximal exercise performance and endurance were evaluated using calorie-restriction animal model. In acute forced swimming test with 10% body weight attached to tail, dietary Lak supplementation increased exercise performance endurance by increasing concentrations of ATP and insulin-like growth factor-1 (IGF-1) under calorie-restriction condition, and decrement of blood lactic acid concentration and increment of muscle ATP content were observed. These results suggest Lak is very effective for decreasing side-effects of obesity therapy using very low calorie diet.