• Title/Summary/Keyword: Rats Tissue distribution

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Study on Pharmacokinetics of a new NSAID SJ-151

  • Kim, Dong-Sup;Na, Han-Kwang;Park, In-Sook;Im, Dong-Suk;Park, Ki-Hwan;Chang, Young-Sup;Lee, Young-Keun
    • Proceedings of the Korean Society of Applied Pharmacology
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    • 1997.04a
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    • pp.106-106
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    • 1997
  • Cinmetacin, one of the candidate of NSAID of arylacetate group was developed into a prodrug SJ-151 with butendiol group to minimize its gastrointestinal side effects. We studied its excretion and distribution after single oral administration in rats. Male rats were orally administered with 30, 60, 80 or 120mg/kg of SJ-151 and their urine and stool were collected at 0, 6, 12, 24 and 48 hour after administration. To evaluate its tissue distribution, 120mg/kg of SJ-151 was orally given and samples of blood, liver, kidney and brain were taken at 0.5, 1, 2, 4, 8, 24, and 48 hour of administration. As results, less than 0.1% of administered SJ-151 was detected in 48 hour collected urine as its metabolite cinmetacin. 33-50% of administered SJ-151 was observed in 48 hour collected stool as SJ-151. 3-7% of excreted SJ-151 was observed in 48 hour collected stool as cinmetacin. SJ-151 and cinmetacin were not detected in the brain regardless of dosage. SJ-151 was detected neither in kidney nor in liver. Only cinmetacin was observed in both organs with kidney concentrations higher than liver throughout the observation period. On the whole, organ concentration of cinmetacin fluctuated through 0.1-1.5 times that of plasma. As no reports on the metabolism of SJ-151 or cinmetacin in specific organs has been published yet, any detailed explanation of these results needs further study and the plasma concentration profile of rats showed remarkable interspecies difference with dogs.

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A study on the effect comparative of acanthopanax stem bark (ASB) and acanthopanax root bark (ARB) on the monosodium iodoacetate (MIA)-induced osteoarthritis rats (오가피(五加皮) 수피(樹皮)와 근피(根皮)의 MIA 유도 골관절염 흰쥐에 미치는 영향 비교)

  • Sim, Woo-Hyung;Seo, Bu-Il
    • The Korea Journal of Herbology
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    • v.33 no.5
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    • pp.53-66
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    • 2018
  • Objectives : This study was designed to compare the effects of acanthopanax stem bark (ASB) and acanthopanax root bark (ARB) on the monosodium iodoacetate (MIA)-induced osteoarthritis rats. Methods : The antioxidant activities were evaluated through radical scavenging assays using 2,2'-azino-bis (3-ethylbenzothiazoline-6-sulphonic acid) (ABTS) radicals and 1,1-diphenyl-2-picrylhydrazyl (DPPH) radicals. Also, we examined total poly phenol and flavonoids contents. Osteoarthritis was caused by injection MIA($50{\mu}{\ell}$ with $80mg/m{\ell}$) into the knee joint cavity of rats. Rats were divided by 4 groups (normal group, control group, ASB treated group, ARB treated group, each n=6). The changes in the levels of reactive oxygen species (ROS), alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in serum were analyzed after experiment. Also, the anti-oxidant, inflammatory protein levels were investigated western blot analysis. Knee joint tissue, histopathological observation hematoxylin & eosin staining and safranin-O staining were measured. Results : In the present study, ARB treated group showed superior inhibitory effects on the inflammatory parameters than the ASB treated group. ARB aqueous extract was effective in antioxidant measurements. The administration of ARB showed a significant reduction of changes in relative hind paw weight distribution. Morever, it decreased ROS, ALT and AST levels in serum, compared with those of the control rats. The ARB administration inhibited the biomarkers of inflammatory in tissues. Conclusions : ASB aqueous extract and ARB aqueous extract have a great effect on osteoarthritis, and ARB aqueous extract has excellent effect on osteoarthritis through antioxidant and anti-inflammation.

AN IMMUNOHISTOCHEMICAL STUDY ON DNA SYNTHESIS OF SALIVARY GLAND TISSUE CEllS AND ENDOTHELIAL CELL AFTER IRRADIATION (방사선조사 후 타액선 세포와 혈관 내피세포의 DNA합성에 관한 면역조직학적 연구)

  • Shin Jong-Sup;You Dong-Soo
    • Journal of Korean Academy of Oral and Maxillofacial Radiology
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    • v.21 no.2
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    • pp.183-197
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    • 1991
  • After single fraction of 2, 5, 10 Gy irradiation on submandibular gland of 40 male rats, weighing 150gm, respectively, these animal were sacrificed two hours after 0.1㎎/g bromodeoxyuridine (Sigma) peritoneal injection in 1, 3, 7, 15 hours, 1, 3, 7 days after irradiation. And excised submandibular gland were fixed in Carnoy's and Bouin's solution for 2 hours. Paraffin sections were stained with H&E, and PAS for the observation of the change of salivary gland tissue, and with Feulgen for the study of the DNA distribution, and immunohistochemically stained with anti-bromodeoxyuridine (Sanbyo Co.) for detection of DNA synthetic cells in order to study the distribution of DNA synthetic cells of salivary gland tissue and endothelium after irradiation in 5 different sites of 6 slides on X 200 high power field. The results were as followings. 1. In PAS staining 3 days after 5Gy irradiation, decreased mucine secretion of serous cells were found, and 7 days after l0Gy irradiation, decreased mucine secretion of mucous cells were found. 2. In histopathologic features, degeneration of serous cells were found in 3 days after 2 Gy irradiation and there was little change in mucous cells and excretory duct cells. 3. In Feugen staining, 3 days after 2 Gy, 5 Gy irradiation, more high percentage of DNA synthetic cells were found in intercalated duct cells, striated duct cells and excretory duct cells than in BrdU staining. 4. In immunohistochemical features, DNA synethsis of serous cells and granular convoluted tubular cells abruptly decreased in early period after irradiation and showed no recovery in 7 days after irradiation but there was an increase in DNA synthesis of intercalated duct cells, striated duct cells and excretory duct cells, which have less S-phase cells comparatively, in 7 days after 2 Gy, 5 Gy irradiation. 5. In immunohistochemical features, the DNA synthesis of endothelial cells was continuously decreased after irradiation but showed slight increase in 7 days after 2 Gy and S Gy irradiation.

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Effects of aqueous extract from Taxillus chinensis on monosodium iodoacetate-induced osteoarthritis in rats (Monosodium iodoacetate로 유도된 골관절염 동물모델에서 상기생 물추출물의 효과)

  • Kim, Joong Sun;Lee, A Yeong;Moon, Byeong Cheol;Kim, Hyo Seon;Kim, Wook Jin;Kim, Chul;Choi, Goya;Kim, Seung-Hyung;Chun, Jin Mi
    • The Korea Journal of Herbology
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    • v.33 no.5
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    • pp.81-88
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    • 2018
  • Objectives : The aim of this study was to investigate the protective effects of an aqueous extract from Taxillus chinensis (DC.) Danser (TCE) in Monosodium iodoacetate (MIA)-induced osteoarthritis (OA) rat model. Methods : Sprague Dawley male rats were divided into the following four groups (n=6 per group): Normal (saline control), MIA (MIA-induced OA with vehicle), TCE (MIA-induced with TCE treatment), and IM (MIA-induced with indomethacin treatment). Rats in which OA was induced by MIA were treated with TCE (200 mg/kg) or indomethacin (1 mg/kg) for 4 weeks. Weight-bearing on the hind legs and body weights were measured weekly. At the end of the experiment (3 weeks after MIA injection), serum aspartate aminotransferase and alanine aminotransferase levels were measured to assess the liver toxicity induced by TCE. Its effects on serum inflammatory cytokine levels and tissue histopathology were also evaluated. Results : TCE restored the hind limb weight-bearing distribution. Serum levels of Interleukin 6 (IL-6), Tumor necrosis factor alpha (TNF-${\alpha}$) and Leukotriene B4 (LTB4) were significantly higher in the MIA group than in the Normal group, but serum IL-6 levels were significantly lower in the TCE group. In the TCE group, the synovial membrane was protected in hematoxylin and eosin and Safranin-O staining, respectively. Conclusions : TCE recovered the hind paw weight bearing distribution, inhibited the production of inflammatory cytokine, and protected synovial tissue and cartilage in the OA rat model. Therefore, TCE appears to be an effective therapeutic agent for treating OA and OA-related symptoms.

Distribution of Murine Tissue Specific ${\gamma}$-Glutamyltransferase: -Comparison of Six Monoclonal Antibody Applications in Enzyme Linked Immunosorbent Assay, Radioimmunoassay, Immunohistochemistry, and Autoradiography- (${\gamma}$-Glutamyltransferase의 조직내 분포에 관한 연구 -단일클론항체의 효소면역측정법, 방사면역측정법, 면역조직화학검사, 자가방사기록검사 적용에 관하여 -)

  • Kim, Meyoung-Kon;Park, Youn-Kyu;Ryu, Chong-Kun
    • The Korean Journal of Nuclear Medicine
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    • v.28 no.1
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    • pp.112-123
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    • 1994
  • ${\gamma}$-Glutamyltransferase (GGT: E.C. 2.3.2.2.) is a glycoprotein enzyme which is involved in glutathione metabolism and amino acid transport through the plasma membrane. It is distributed widely in several organs including liver and kidney. Several isozymes of GGT have been reported and some of the isozymes may be associated with hepatocarcinogenesis. We have produced six monoclnal antibodies (mAbs) against GGT purified from the liver of 2-acetamidofluorene (AAF) treated rats. All of the six mAbs were obtained by immunizing mice with liver GGT Six hybridomas which produced anti-GGT Abs were extensively subcloned and injected into the peritoneal cavity of BALB/c mice to obtain large quantities of Abs. These mAbs were purified from ascites by ammonium sulfate precipitation and protein A sepharose CL-4B column chromatography. Using these mAbs we preformed enzyme-linked immunosorbent assay (ELISA), radioimmunoassay (RIA), immunohistochemistry (IHC), and autoradiography (ARG) to study the distribution of GGT isozyme in tissue. The results indicate that GGT-mAb 1 is specific for the AAF treated liver GGT, GGT-mAb 5 for the normal liver GGT, and GGT-mAb 6 for the normal kindey GGT. These mAbs may be used to evaluate the distribution of GGT isozymes in different tissues.

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THE EFFECTS OF HYPERBARIC OXYGEN THERAPY ON PERIODONTAL WOUND HEALING OF REPLANTED RAT TOOTH (고압산소요법이 재식치아 치주조직치유에 미치는 영향)

  • Chung, Ill-Young;Kim, Kwang-Chul;Lee, Keung-Ho
    • Journal of the korean academy of Pediatric Dentistry
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    • v.24 no.1
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    • pp.41-57
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    • 1997
  • The present study investigated the effects of hyperbaric oxygen therapy on periodontal wound healing of replanted rat tooth. 80 rats (Sprague-Dawley strain) weighting $130{\pm}5gm$ were selected and divided into experimental and control group, each group consisting of 40 rats. Rats were administered 0.4% ${\beta}$-aminoproprionitrile for 5 days to achieve gentle tooth extraction. The maxillary first molars were extracted under anesthesia with pentobarbital, washed in sterile distilled water, treated with bacterial collagenase to remove collagen fibers on the root surfaces. After washing in water overnight, the mesial root surface were demineralized by application of citric acid, washed, dried and stored at $4^{\circ}C$. Immediately after tooth extraction and bleeding control, the treated molars extracted previously from other rats were replanted. The experimental group was exposed to hyperbaric oxygen at 2.5 atm. for 2 hrs. a day during experimental period. Eight animals of each group were sacrificed 1, 3, 6, 8, 10 days after reimplantation of teeth by intracardiac perfusion with 4% paraformaldehyde. The replanted molars and surrounding tissues were cut, demineralized, dehydrated and embedded in paraffin. Sections were stained with azan, toluidine blue and hematoxylin. Some other sections were stained by means of immunostaining achieved by the avidinbiotin complex method. The results as follows; 1. Experimental group showed fast healing of gingival epithelium. 2. Macrophage and newly formed blood vessels appeared early in the gingival connective tissue of experimental group. 3. Experimental group showed fast, abundant fibroblast proliferation and regularity of collagen fiber. 4. In both group, collagen was distributed along the collagen fiber. The distribution was strong and regular in the experimental group. 5. In the regenerated periodontal ligament of experimental group, fibers showed regular arrangement and invaded root surface fast.

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The Effect of Platelet-rich Plasma on Wounds of OLETF Rats Using Expression of Matrix Metalloproteinase-2 and -9 mRNA

  • Shin, Ho-Seong;Oh, Hwa-Young
    • Archives of Plastic Surgery
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    • v.39 no.2
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    • pp.106-112
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    • 2012
  • Background : Complicated diabetic patients show impaired, delayed wound healing caused by multiple factors. A study on wound healing showed that platelet-rich plasma (PRP) was effective in normal tissue regeneration. Nonetheless, there is no evidence that when platelet-rich plasma is applied to diabetic wounds, it normalizes the diabetic wound healing process. In this study, we have analyzed matrix metalloproteinase (MMP)-2, MMP-9 expression to investigate the effect of PRP on diabetic wounds. Methods : Twenty-four-week-old male Otsuka Long-Evans Tokushima Fatty rats were provided by the Tokushima Research Institute. At 50 weeks, wounds were arranged in two sites on the lateral paraspinal areas. Each wound was treated with PRP gel and physiologic saline gauze. To determine the expression of MMP-2, MMP-9, which was chosen as a marker of wound healing, reverse transcription polymerase chain reaction (RT-PCR) was performed and local distribution and expression of MMP-2, MMP-9 was also observed throughout the immunohistochemical staining. Results : RT-PCR and the immunohistochemical study showed that the levels of MMP-2, MMP-9 mRNA expression in PRP applied tissues were higher than MMP-2, MMP-9 mRNA expression in saline-applied tissues. MMP-9 mRNA expression in wounds of diabetic rats decreased after healing began to occur. But no statistical differences were detected on the basis of body weight or fasting blood glucose levels. Conclusions : This study could indicate the extracellular matrix-regulating effect observed with PRP. Our results of the acceleration of wound healing events by PRP under hyperglycemic conditions might be a useful clue for future clinical treatment for diabetic wounds.

Age-dependent expression of ion channel genes in rat

  • Sung-Cherl Jung;Tong Zhou;Eun-A Ko
    • The Korean Journal of Physiology and Pharmacology
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    • v.27 no.1
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    • pp.85-94
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    • 2023
  • Ion channels regulate a large number of cellular functions and their functional role in many diseases makes them potential therapeutic targets. Given their diverse distribution across multiple organs, the roles of ion channels, particularly in age-associated transcriptomic changes in specific organs, are yet to be fully revealed. Using RNA-seq data, we investigated the rat transcriptomic profiles of ion channel genes across 11 organs/tissues and 4 developmental stages in both sexes of Fischer 344 rats and identify tissue-specific and age-dependent changes in ion channel gene expression. Organ-enriched ion channel genes were identified. In particular, the brain showed higher tissue-specificity of ion channel genes, including Gabrd, Gabra6, Gabrg2, Grin2a, and Grin2b. Notably, age-dependent changes in ion channel gene expression were prominently observed in the thymus, including in Aqp1, Clcn4, Hvcn1, Itpr1, Kcng2, Kcnj11, Kcnn3, and Trpm2. Our comprehensive study of ion channel gene expression will serve as a primary resource for biological studies of aging-related diseases caused by abnormal ion channel functions.

Pharmacokinetic studies on ADME of G009

  • Deuk, Han-Man;Hoon Jeong;Lee, June-Woo;Kim, Su-Ung;Lee, Seung-Yong;Song, Jae-Jin;Chung, Sung-Kyun;Kim, Kee-Nam;Back, Seong-Jin
    • Proceedings of the Korean Society of Applied Pharmacology
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    • 1995.04a
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    • pp.108-108
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    • 1995
  • Pharmacokinetic studies on time-course of blood levels, tissue distribution, and excretion of G009, a potential hepatoprotective agent, were performed in male rats after a single oral dose(20mg/kg) of $\^$14/C-labelled G009. The radioactivity concentrations in plasma during 0~3 hours are low, but subsequently increase to a maximum at 12 hours after dosing. $\^$14/C-G009 was well distributed to all tissue. Tissue concentration profiles of radioactivity vary among tissues on time-course after administration. G009(single oral dosage) was distributed and/or absorbed at gastric intestines and excretional organs for initial time of 0-7 hours, and distributed to most tissue at 12-24 hours. In special, the concentration of radioactivity in tiller at 48 hours were 1% of total radioactivity of $\^$14/C-G009 administered. The expired air, urinary and fecal excretion of radioactivity within 24hours after administration were 61.5%, 1.9% and 21.2% of total radioactivity of $\^$14/C-G009 administered. The biliary excretion of radioactivity in rat increased slightly for 0-6 hours after administration. The biliary excretion of radioactivity within 48hours were 1.97%.

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Effects of Green Tea Catechin on Bone Disorder in Long-Term Cadmium Treated Rats (만성 카드뮴 처치 쥐에서 골조직 장애에 미치는 녹차 Catechin의 영향)

  • 최정화;김용진;이순재
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.30 no.6
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    • pp.1253-1259
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    • 2001
  • The purpose of this study was to investigate the effects of green tea catechin on change of bone tissue in long-term cadmium treated rats. Sprague-Dawley male rats weighing 100$\pm$10 g were randomly assigned to one normal group and three cadmium treated groups. Cadmium groups were classified to catechin free diet group (Cd-0C group), 0.25% catechin diet group (Cd-0.25C group) and 0.5% catechin diet group (Cd-0.5C group) according to the levels of catechin supplement. Animals were raised for 20 weeks. Cadmium were supplied as drinking water of 50 ppm Cd$^{2+}$. Effects of catechin were analyzed on changes of bony tissue in long-term cadmium treated rats by determining the accumulated cadmium in bone and bone mineral density and micro- photographs of bony tissue. The cadmium accumulation of tibia and femur were higher in Cd-treated groups than in normal group, but they was lowered by catechin supplementation. The bone mineral density (BMD) of tibia and femur in Cd-0C group was significantly lower than in normal group, but it of catechin supplemetation group was similar to normal group. Microphological changers were appeared under a light microscope and an electro microscope reveal no structural changes in bony spicules, marrow cell distribution and cellular morphology in all groups. The bone weight and length tend to decrease in Cd-0C groups. Catechin supplementation in long-term cadmium treated rats depressed the cadmium accumulation in bony tissue that led to improve the bone mineral density in tibia and femur.r.

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