• Title/Summary/Keyword: Model Rat

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ᴅ-Xylose as a sugar complement regulates blood glucose levels by suppressing phosphoenolpyruvate carboxylase (PEPCK) in streptozotocin-nicotinamide-induced diabetic rats and by enhancing glucose uptake in vitro

  • Kim, Eunju;Kim, Yoo-Sun;Kim, Kyung-Mi;Jung, Sangwon;Yoo, Sang-Ho;Kim, Yuri
    • Nutrition Research and Practice
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    • v.10 no.1
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    • pp.11-18
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    • 2016
  • BACKGROUND/OBJECTIVES: Type 2 diabetes (T2D) is more frequently diagnosed and is characterized by hyperglycemia and insulin resistance. $\small{D}$-xylose, a sucrase inhibitor, may be useful as a functional sugar complement to inhibit increases in blood glucose levels. The objective of this study was to investigate the anti-diabetic effects of $\small{D}$-xylose both in vitro and stretpozotocin (STZ)-nicotinamide (NA)-induced models in vivo. MATERIALS/METHODS: Wistar rats were divided into the following groups: (i) normal control; (ii) diabetic control; (iii) diabetic rats supplemented with a diet where 5% of the total sucrose content in the diet was replaced with $\small{D}$-xylose; and (iv) diabetic rats supplemented with a diet where 10% of the total sucrose content in the diet was replaced with $\small{D}$-xylose. These groups were maintained for two weeks. The effects of $\small{D}$-xylose on blood glucose levels were examined using oral glucose tolerance test, insulin secretion assays, histology of liver and pancreas tissues, and analysis of phosphoenolpyruvate carboxylase (PEPCK) expression in liver tissues of a STZ-NA-induced experimental rat model. Levels of glucose uptake and insulin secretion by differentiated C2C12 muscle cells and INS-1 pancreatic ${\beta}$-cells were analyzed. RESULTS: In vivo, $\small{D}$-xylose supplementation significantly reduced fasting serum glucose levels (P < 0.05), it slightly reduced the area under the glucose curve, and increased insulin levels compared to the diabetic controls. $\small{D}$-xylose supplementation enhanced the regeneration of pancreas tissue and improved the arrangement of hepatocytes compared to the diabetic controls. Lower levels of PEPCK were detected in the liver tissues of $\small{D}$-xylose-supplemented rats (P < 0.05). In vitro, both 2-NBDG uptake by C2C12 cells and insulin secretion by INS-1 cells were increased with $\small{D}$-xylose supplementation in a dose-dependent manner compared to treatment with glucose alone. CONCLUSIONS: In this study, $\small{D}$-xylose exerted anti-diabetic effects in vivo by regulating blood glucose levels via regeneration of damaged pancreas and liver tissues and regulation of PEPCK, a key rate-limiting enzyme in the process of gluconeogenesis. In vitro, $\small{D}$-xylose induced the uptake of glucose by muscle cells and the secretion of insulin cells by ${\beta}$-cells. These mechanistic insights will facilitate the development of highly effective strategy for T2D.

Effect of Persistant Mild Hyperglycemic Hyperinsulinemia on Development of Insulin Resistance in Rats (지속적인 경한 고혈당과 고인슐린증이 인슐린 저항성의 발생에 미치는 영향)

  • Kim, Yong-Woon;Park, Jin-Hyun;Park, So-Young;Kim, Jong-Yeon;Lee, Suck-Kang
    • Journal of Yeungnam Medical Science
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    • v.12 no.2
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    • pp.269-281
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    • 1995
  • The effect of persistant mild hyperglycemic hyperinsulinemia on the development of the insulin resistance in rats was studied in vivo. Also, the characteristics of the insulin resistance compared with the insulin resistance of STZ diabetic rats. Persistant mild hyperglycemic hyperinsulinemic rat model was produced by ingestion of glucose polymer for 8 days. The glucose disappearance and infusion rate was measured by hyperinsulinemic euglycemic clamp technique at steady state of blood glucose and insulin levels. The clamped level of blood glucose was 100 mg/dl, and the clamped levels of insulin were $70{\mu}U/ml$ (physiologic condition) and $3000{\mu}U/ml$ (supramaximal condition). Hepatic glucose producticon rate was calculated using measured data. And the glycogen synthetic capacity of skeletal muscle(soleus) and liver was measured after 2 hours of hyperinsulinemic euglycemic clamp study. The glucose disappearance and glucose infusion rate in glucose polymer group was decreased in the both physiological and supramaximal insulin level compared to the rate of the normal control group. The rate of STZ diabetic group wase lowest at supramaximal insulin level among two another experimental groups. The hepatic glucose production rate of glucose polymer group was decreased compared to normal control but increased in STZ diabetic group. The glycogen synthetic capacity of skeletal muscle and liver of glucose polymer group was not significantly different from normal control group, but it was markdly decreased in STZ diabetic group. These results suggest that persistant mild hyperglycemic hyperinsulinemia may induce insulin resistance, but glycogen synthetic capacity is intact.

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Wound Healing Effect of Low Molecular PDRN on Experimental Surgical Excision Rat Model (저분자화된 Polydeoxynucleotide (PDRN)의 흰쥐에 대한 외과적 창상 치유 효과)

  • Yun, Jong-Kuk;Yoon, Hye-Eun;Park, Jeong-Kyu;Kim, Mi Ryeo;Kim, Dae-Ik
    • Journal of the Society of Cosmetic Scientists of Korea
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    • v.41 no.4
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    • pp.401-411
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    • 2015
  • This study was performed to investigate the wound healing effect of skin regeneration cosmetics utilizing low molecular weight Polydeoxynucleotide (PDRN). High purity PDRN was prepared from salmon testes poly-deoxy-ribonucleotide through protein and toxin removal process and molecular weight reduction. In order to evaluate the wound healing effect of PDRN in SD rats, 4 sites of dorsal skin of each animal were excised by using biopsy punch and $500{\mu}L$ of test solution was topically applied once daily for 4 weeks. The tissue changes were observed for every week during the application periods. After applying the PDRN to the wound, the skin was cut flower and contraction of the wounds more quickly, and the coating of PDRN in the wound area was reduced significantly as compared to the positive control group $Fucidin^{(R)}$ applied. The microscopic observation of stained tissue showed that a positive control was most rapid in re-epithelialization ability followed by the PH group, PDRN group, HA group. In addition, transforming growth factor ($TGF-{\beta}$) and vascular endothelial growth factor (VEGF), such as in the growth factor was similar to the results of staining of tissue lesions. In conclusion, it is determined that the low molecular weight PDRN has the therapeutic effect to the wound, and could be used as a functional material of cosmetics and medical industries.

The Protective Effect of Arecae Semen and Coptidis Rhizoma in a Chronic Reflux Esophagitis Rat Model (만성 역류성 식도염 모델에서 빈랑(檳榔)와 황련(黃連) 복합물의 보호 효과)

  • Lee, Se Hui;Lee, Jin A;Shin, Mi-Rae;Lee, Ji Hye;Roh, Seong-Soo
    • The Journal of Internal Korean Medicine
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    • v.42 no.1
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    • pp.11-24
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    • 2021
  • Objective: Chronic reflux esophagitis (CRE), characterized by esophageal mucosa ulcer, is caused by continuous backflow of gastric acid and consequent inflammation due to unstable gastroesophageal sphincter. The aim of the present study was to clarify the effect of an Arecae Semen and Coptidis Rhizoma mixture (AC-mix) on CRE. Methods: CRE was surgically induced in SD rats with three experimental groups used: normal; CRE control; and CRE treatment (200 mg/kg AC-mix). Blood and esophageal tissue were collected after two weeks of drug administration. The anti-oxidant activity of the AC-mix was measured by total polyphenol and total flavonoid contents as well as by radical scavenging activity with protein levels evaluated using western blotting. Results: CRE damage to the esophageal mucosa was significantly reduced in the AC-mix group as compared with the controls, and administration of the AC-mix was seen to inhibit NF-κBp65 activity. Consequently, the inactivation of NF-κBp65 significantly inhibited inflammatory mediators such as COX-2 and iNOS. Moreover, the anti-oxidant enzyme HO-1 significantly increased through activation of the Nrf2-Keap1 pathway. Matrix metalloproteinase-2 (MMP-2), which can break down collagen from the basement membrane and extracellular matrix, was decreased following AC-mix treatment, and elevated levels of MMP-2 were regulated by its tissue inhibitor. Conclusions: These results show that AC-mix can alleviate esophageal mucosa ulcer though inhibition of the NF-κBp65 inflammatory pathway and enhancement of the anti-oxidant Nrf2-Keap1 pathway.

Adjuvant therapy with 1% alendronate gel for experimental periodontitis treatment in rats

  • de Campos Kajimoto, Natalia;de Paiva Buischi, Yvonne;Loomer, Peter Michael;Bromage, Timothy G.;Ervolino, Edilson;Fucini, Stephen Enrico;Pola, Natalia Marcumini;Pirovani, Beatriz Ommati;Morabito, Maria Juliana Sismeiro;de Almeida, Juliano Milanezi;Furlaneto, Flavia Aparecida Chaves;Nagata, Maria Jose Hitomi
    • Journal of Periodontal and Implant Science
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    • v.51 no.6
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    • pp.374-385
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    • 2021
  • Purpose: The aim of this study was to evaluate the effects of locally delivered 1% alendronate (ALN) gel used as an adjunct to non-invasive periodontal therapy. Methods: Ligature-induced periodontitis was performed in 96 rats. The ligature was tied in the cervical area of the mandibular left first molar. The animals were randomly divided into 4 groups: 1) NT, no treatment; 2) SRP, scaling and root planning; 3) SRP/PLA, SRP followed by filling the periodontal pocket with placebo gel (PLA); and 4) SRP/ALN, SRP followed by filling the periodontal pockets with 1% ALN gel. Histomorphometric (percentage of bone in the furcation region [PBF]) and immunohistochemical (receptor activator of nuclear factor-κB ligand, osteoprotegerin, and tartrate-resistant acid phosphatase) analyses were performed. Data were statistically analyzed, with the threshold of statistical significance set at P≤0.05. Results: The SRP, SRP/PLA, and SRP/ALN groups presented a higher PBF than the NT group (P≤0.01) at 7, 15, and 30 days. The SRP/ALN group presented a higher PBF than the SRP/PLA group in all experimental periods, as well as a higher PBF than the SRP group at 15 and 30 days. No differences were observed in the immunohistochemical analyses (P>0.05 for all). Conclusions: Locally delivered 1% ALN gel used as an adjunct to SRP enhanced bone regeneration in the furcation region in a rat model of experimental periodontitis.

Diffusion Tensor-Derived Properties of Benign Oligemia, True "at Risk" Penumbra, and Infarct Core during the First Three Hours of Stroke Onset: A Rat Model

  • Chiu, Fang-Ying;Kuo, Duen-Pang;Chen, Yung-Chieh;Kao, Yu-Chieh;Chung, Hsiao-Wen;Chen, Cheng-Yu
    • Korean Journal of Radiology
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    • v.19 no.6
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    • pp.1161-1171
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    • 2018
  • Objective: The aim of this study was to investigate diffusion tensor (DT) imaging-derived properties of benign oligemia, true "at risk" penumbra (TP), and the infarct core (IC) during the first 3 hours of stroke onset. Materials and Methods: The study was approved by the local animal care and use committee. DT imaging data were obtained from 14 rats after permanent middle cerebral artery occlusion (pMCAO) using a 7T magnetic resonance scanner (Bruker) in room air. Relative cerebral blood flow and apparent diffusion coefficient (ADC) maps were generated to define oligemia, TP, IC, and normal tissue (NT) every 30 minutes up to 3 hours. Relative fractional anisotropy (rFA), pure anisotropy (rq), diffusion magnitude (rL), ADC (rADC), axial diffusivity (rAD), and radial diffusivity (rRD) values were derived by comparison with the contralateral normal brain. Results: The mean volume of oligemia was $24.7{\pm}14.1mm^3$, that of TP was $81.3{\pm}62.6mm^3$, and that of IC was $123.0{\pm}85.2mm^3$ at 30 minutes after pMCAO. rFA showed an initial paradoxical 10% increase in IC and TP, and declined afterward. The rq, rL, rADC, rAD, and rRD showed an initial discrepant decrease in IC (from -24% to -36%) as compared with TP (from -7% to -13%). Significant differences (p < 0.05) in metrics, except rFA, were found between tissue subtypes in the first 2.5 hours. The rq demonstrated the best overall performance in discriminating TP from IC (accuracy = 92.6%, area under curve = 0.93) and the optimal cutoff value was -33.90%. The metric values for oligemia and NT remained similar at all time points. Conclusion: Benign oligemia is small and remains microstructurally normal under pMCAO. TP and IC show a distinct evolution of DT-derived properties within the first 3 hours of stroke onset, and are thus potentially useful in predicting the fate of ischemic brain.

Change in the Levels of Intracellular Antioxidants during Aging of Articular Chondrocytes and Cartilage (연골세포 및 관절연골의 노화 과정에서 세포내 항산화 인자들의 변화)

  • Kim, Kang Mi;Kim, Yoon Jae;Kim, Jong Min;Sohn, Dong Hyun;Park, Young Chul
    • Journal of Life Science
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    • v.29 no.8
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    • pp.888-894
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    • 2019
  • Cartilage diseases, such as rheumatoid arthritis (RA) and osteoarthritis (OA), are associated with the loss of chondrocytes and degradation of articular cartilage. Recent studies revealed that inflammatory reactive oxygen species (ROS) and age-related oxidative stress can affect chondrocyte activity and cartilage homeostasis. We investigated changes in the levels of intracellular antioxidants during cellular senescence of primary chondrocytes from rat articular cartilages. Cellular senescence was induced by serial subculture (passages 0, 2, 4, and 8) of chondrocytes and measured using specific senescence-associated ${\beta}$-galactosidase ($SA-{\beta}-gal$) staining. ROS production increased significantly in the senescent chondrocytes. In addition, total glutathione (GSSG/GSH) and superoxide dismutase (SOD) levels and heme oxygenase-1 (HO-1) expression increased in senescent chondrocytes induced by serial subculture. Analysis of changes in intracellular antioxidant levels in articular cartilage from rats of different ages (5, 25, 40, and 72 wk) revealed that total glutathione levels were highest after 40 wk and slightly decreased after 72 wk as compared with those after 25 wk. SOD and HO-1 expression levels increased in accordance with age. Based on these results, we conclude that intracellular antioxidants may be associated with cartilage protection against excessive oxidative stress in the process of chondrocyte senescence and age-related cartilage degeneration in an animal model.

Evaluation of the Effect of Oriental Medicinal Herbs with Growth Factors on Bone Development using the SD Strain Rat Model in the Growth Period (뼈 발달에 관한 성장인자를 가진 한약재가 성장기 흰쥐 동물모델에 미치는 영향)

  • Sim, Jae-Won;Ahn, Hee-Young;Sim, So-Yeon;Kim, Hee-Young;Cho, Yong-Ju;Cho, Young-Su
    • Journal of Life Science
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    • v.29 no.5
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    • pp.614-620
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    • 2019
  • The purpose of this study was to examine the growth plate, femoral bone length, bone mineral density, and blood composition in various experimental animals fed with oriental medicinal herbs containing growth factors. First, the lengths of the bone growth plates of the positive control (PC) group (fed with Astragalus membranaceus) and the Gh-199 and Sh-188 groups were increased when compared to group N. The Gh-199 group showed a greater increase in bone growth when compared with the PC group. In terms of the femoral bone length and bone mineral density, the effect of both Gh-199 and Sh-188 powders were as good as those of the PC group, and the Gh-199 powder showed a positive effect. Conversely, in the PC group, unlike the Gh-199 and Sh-188 groups, the aspartate aminotransferase(AST) and alanine aminotransferase(ALT) activities in the blood were increased, indicating that A. membranaceus is toxic to the body. Both the PC and Sh-188 groups also showed higher insulin-like growth factor-1(IGF-1) activity when compared with the Gh-199 group. Overall, the bone growth plate, femoral bone length, and bone mineral density measurements, and the blood analysis showed positive results in the group treated with Gh-199, and no specific toxicity of the herbal medicine in the body was evident.

The Preventive Effect of Bacillus polyfermenticus KJS-2 and Bacillus mojavensis KJS-3 on Triton WR-1339-induced Hyperlipidemia (Triton WR-1339로 유도된 고지혈증에 대한 Bacillus polyfermenticus KJS-2와 Bacillus mojavensis KJS-3의 예방효과)

  • Lee, Jin Young;Lee, Seung Jae;Kim, Hyung Hoi;Kang, Jae Seon
    • Journal of Life Science
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    • v.31 no.3
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    • pp.346-355
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    • 2021
  • The purpose of this study was to evaluate the possibility that administration of Bacillus polyfermenticus KJS-2 (BP2), Bacillus mojavensis KJS-3 (Moja3), and their mixtures could control serum lipid levels. We observed changes in the blood cell level, metabolic function evaluation, and blood lipid levels after two weeks of oral administration of these microbial strains to hyperlipidemia-induced rats. Measurements of major cell changes in the white blood cells (WBC) indicated no significant effects due to the administration of the microbial strains. Platelet (PLT) levels decreased by 18.4% in the Triton WR-1339-treated group (NCON) and recovered to the control (CON) group levels in the positive control (PCON) group and the microbial strain-administered groups (p<0.05). No functional changes were observed in red blood cells (RBC) by Triton WR-1339-induced hyperlipidemia. The blood AST, ALT, BUN, and creatinine levels did not indicated effects on liver and kidney function, and all rats administered the microbial mixture recovered. The blood lipid levels in the microbe-treated groups indicated reduced levels of triglyceride (TG) and total cholesterol (TC), and increased levels of serum HDL cholesterol. The HMG-CoA inhibition rate of 7-O-succinyl macrolactin A (SMA) produced by BP2 showed similar activity at a concentration of 1,000 times lower than that achieved with atorvastatin. The administration of the microbial strains to the Triton WR-1339-induced rat model of hyperlipidemia resulted in reduced weight gain without affecting the food and water intake. Thus, blood circulation can be improved by controlling serum lipid levels by the combined administration of the BP2 and Moja3 microbial strains.

Ref-1 protects against FeCl3-induced thrombosis and tissue factor expression via the GSK3β-NF-κB pathway

  • Lee, Ikjun;Nagar, Harsha;Kim, Seonhee;Choi, Su-jeong;Piao, Shuyu;Ahn, Moonsang;Jeon, Byeong Hwa;Oh, Sang-Ha;Kang, Shin Kwang;Kim, Cuk-Seong
    • The Korean Journal of Physiology and Pharmacology
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    • v.25 no.1
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    • pp.59-68
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    • 2021
  • Arterial thrombosis and its associated diseases are considered to constitute a major healthcare problem. Arterial thrombosis, defined as blood clot formation in an artery that interrupts blood circulation, is associated with many cardiovascular diseases. Oxidative stress is one of many important factors that aggravates the pathophysiological process of arterial thrombosis. Apurinic/apyrimidinic endonuclease 1/redox factor-1 (Ref-1) has a multifunctional role in cells that includes the regulation of oxidative stress and anti-inflammatory function. The aim of this study was to investigate the therapeutic effect of adenovirus-mediated Ref-1 overexpression on arterial thrombosis induced by 60% FeCl3 solution in rats. Blood flow was measured to detect the time to occlusion, thrombus formation was detected by hematoxylin and eosin staining, reactive oxygen species (ROS) levels were detected by high-performance liquid chromatography, and the expression of tissue factor and other proteins was detected by Western blot. FeCl3 aggravated thrombus formation in carotid arteries and reduced the time to artery occlusion. Ref-1 significantly delayed arterial obstruction via the inhibition of thrombus formation, especially by downregulating tissue factor expression through the Akt-GSK3β-NF-κB signaling pathway. Ref1 also reduced the expression of vascular inflammation markers ICAM-1 and VCAM-1, and reduced the level of ROS that contributed to thrombus formation. The results showed that adenovirus-mediated Ref-1 overexpression reduced thrombus formation in the rat carotid artery. In summary, Ref-1 overexpression had anti-thrombotic effects in a carotid artery thrombosis model and could be a target for the treatment of arterial thrombosis.