• Title/Summary/Keyword: Rat kidney

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Pharmacokinetic Preformulation Study of rH IL-2 (인터루킨-2의 제제설계를 위한 체내 동태학적 연구)

  • Seo, Min-Seok;Shim, Chang-Koo;Kwon, Jong-Bum;Na, Do-Sun;Lee, Sun-Bok;Hahm, Kyung-Soo;Han, Moon-Hi
    • YAKHAK HOEJI
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    • v.34 no.4
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    • pp.238-243
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    • 1990
  • Pharmacokinetic characteristics of recombinant human interleukin-2 (rH IL-2) wre studied in the rat. First, different doses of rH IL-2 ranging from 6,400 to 1,600,000 U/kg were injected intravenously and the effect of dose size on the pharmacokinetics was examined. There was no dose dependency in the pharmacokinetics of rHIL-2 in the dose range of 6,400-40,000 U/kg. But at the dose of 1,600,000 U/kg, there was a severe hemolysis throughout the experiment and the pharmacokinetic parameters such as Vdss and CLt were significantly increased compared to those obtained from lower doses. It also showed that this drug is hardly distributed to the peripheral tissues and hardly eliminated from the body, since the valume of distribution (Vdss) and total body clearance (CLt) were 45-75 ml/kg and 1-2 ml/min/kg, respectively. The Vdss is close to the actual plasma volume and the CLt is less than glomerular filtration rate (GFR). Therefore it seemed that rH IL-2 is distributed only in the plasma pool and hardly filtered in the kidney due to its very large molecular weight. Second, rH IL-2 was administered to the rat via several routes such as hepatic portal vein (PV), intraperitoneal (IP), peroral (PO) and intranasal (IN) routes. The bioavailabilities (BA) of PV, IP, PO and IN routes were 96.8, 4.9, 0 and 0.1%, respectively. The addition of some nasal absorption enhancers such as taurocholate, taurodeoxycholate, glycocholate and glycodeoxycholate did not increase the BA of intranasaly administered rH IL-2. The result is contrast to the effect of these bile salts on the nasal absorption of ${\alpha}-inteferon$. Considering it together with the pharmacokinetic parameters, very large molecular weight of rH IL-2 seemed again to be the cause to very poor membrane permeability.

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Hypolipidemic Effects of Enzyme-Treated Tomato Cake on Sprague-Dawley Rats Fed a High Cholesterol Diet (고 콜레스테롤을 급여한 SD-Rat에서 효소처리한 토마토케이크가 고지혈증에 미치는 영향)

  • Koh, Jong-Ho;Woo, Yong-Ku;Kim, Young-Shik;Oh, Jun-Hyun
    • The Korean Journal of Food And Nutrition
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    • v.25 no.3
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    • pp.590-598
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    • 2012
  • Sprague-Dawley rats were fed with normal (Control), high cholesterol (HC), and high cholesterol containing 3.5% pectin-hydrolytic activity industrial enzyme (Viscozyme L)-treated tomato cakes (ETC) for 4 weeks. In the first week, the weight gain of the HC-fed group was significantly increased to 151.7% (p<0.05), compared to the 115.4% weight gain of the ETC-fed group. The feed efficiencies of the Control- and ETC-fed groups ($0.236{\pm}0.041$ and $0.447{\pm}0.030$, respectively) were significantly different to those of HC-fed group ($0.355{\pm}0.034$) (p<0.05). The kidney and epididymal fat pad of the rats fed with ETC were decreased to 0.303 g and 0.274 g, respectively. There were no significant differences in serum cholesterol, triglycerides, high density lipoprotein-cholesterol or low density lipoprotein-cholesterol levels between the HC- and ETC-fed groups. The ETC-fed group exhibited approximately a 1.1-fold higher total antioxidant activity determined by 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid) radicals than the HC-fed group at 2 weeks. Glutathione peroxidase activity of the ETC-fed group exhibited 2.5-and 1.3-fold increases at 2 and 4 weeks, respectively.

Antioxidative Activity and Produced Condition of Antioxidative Substance by Bacillus sp. FF-7 (Bacillus sp. FF-7에 의한 항산화물질 생산조건과 항산화 활성)

  • Cha, Jae-Young;Kim, Hyo-Jung;Jun, Bang-Sil;Park, Jin-Chul;Ok, Min;Cho, Young-Su
    • Applied Biological Chemistry
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    • v.46 no.3
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    • pp.165-170
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    • 2003
  • The antioxidative activity of antioxidative substances produced from several bacterial strains isolated from fermented foods were tested by $DPPH\;({\alpha},{\alpha}'-diphenyl-{\beta}-picrylhydrazyl)$ free radical scavenging activity. One of the strains showing the highest antioxidative activity was identified as Bacillus sp. based on the morphological, biochemical, physiological characteristics, and 16S rRNA sequence, and named FF-7. The most optimal medium condition for the production of antioxidative substance from Bacillus sp. FF-7 was 2% galactose as carbon source and l% tryptone as nitrogen source. The antioxidative substance produced from FF-7 in these cultural medium was also tested by in vitro experimental models, the peruxidation of linoleic acid and the peroxidation of rat tissues microsomes by using thiobarbituric acid (TBA) for assay of free malondialdehyde production. The antioxidative activity against lipid peroxidation of rat tissues microsomes was shown in the following order; brain 97.50% > heart 79.95% > kidney 77.84% > spleen 77.47% > testis 69.96% > liver 62.45%. The antioxidative substance produced from FF-7 on linoleic acid peroxidation by IBA method was effectively inhibited during four days, and 0.05% BHT (butylated hydroxytoluene) used comparative control was also effectively inhibited. Results showed that the highest antioxidative activity by DPPH method of antioxidative substance produced from Bacillus sp. FF-7 was obtained by supplementing 2% galactose as carton source and l% tryptone as nitrogen source in cultured medium, this substance effectively inhibited the formation of TBARS in brain microsome in vit개 system and in linoleic acid peroxidation.

Effects of Controlled Photoperiod on Body Development in Growing Juvenile Rats

  • Lee, Seung-Hoon;Lee, Han-Ki;Shin, Jin-Hee;Hong, Yun-Kyung;Lee, Sang-Kil;Lee, Sang-Un;Suzuki, Takao;Kang, Tae-Young;Hong, Yong-Geun
    • Reproductive and Developmental Biology
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    • v.34 no.2
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    • pp.89-94
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    • 2010
  • Melatonin is induced by light information through the retina and leads to growth factor activation. Thus, we investigated the effects of melatonin by controlling the photoperiod of growing young rats. Male Sprague-Dawley rats (n=6; 4 weeks old) were divided into two experimental groups: the L/D group (normal photoperiod; light/dark: 12/12 h; lights on at 9:00 a.m.) and the L/L group (light/light: 24 h). Rat body weight and food consumption were measured daily for 8 weeks. After 8 weeks, the rats were anesthetized with a mixture of ketamine (50 mg/kg) and xylazine (10 mg/kg) and sacrificed. Tissue was then collected for RNA isolation (from brain, heart, liver, kidney, adrenal gland, testis, tibia, hind limb muscles). Also, serum was isolated from blood using a centrifugal separation. The L/L group had significantly lower body weight than the L/D group from 4 to 6 weeks (p<0.05). The L/D group had increased tissue mass, compared with the L/L group, but the difference was not statistically significant. The L/D group had a significantly higher melatonin concentration than the L/L group between the hours of midnight and 2:00 a.m (p<0.01). These results indicate that photoperiod length may affect the secretion of melatonin from the pineal gland. Also, the reduction of nocturnal melatonin secretion may retard the development of growing young rats. In future studies, we plan to compare exogenous melatonin administration with endogenous melatonin concentration induced by photoperiod control. Moreover, we will confirm whether the effects seen in pathological animal models can be reversed by controlling the photoperiod.

Effects of Bujasasim-tang Ethanol Extract on Oxidative Stress, Inflammation and Osteoarthritic Rat Model (부자사심탕(附子瀉心湯)이 산화적 손상, 염증 및 골관절염 병태모델에 미치는 영향)

  • Woo, Chang-Hoon;Oh, Min-Seok
    • Journal of Korean Medicine Rehabilitation
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    • v.25 no.2
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    • pp.15-35
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    • 2015
  • Objectives This study was performed to investigate the effects of Bujasasim-tang ethanol extract (BST) on oxidative stress, inflammation and osteoarthritic rat model. Methods To ensure safety of BST, heavy metal levels were measured and cytotoxicity test was done. In vitro, To evaluate antioxidative effects of BST, total phenolic contents, 1,1-diphenyl-2-picryl-hydrazyl (DPPH), 2,2'-azino-bis-(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) scavenging activity, reactive oxygen species (ROS) levels were measured. Also, to evaluate anti-inflammatory effects of BST treated group, total nitric oxide (NO) and pro-inflammatory cytokines (IL-$1{\beta}$, IL-6, TNF-${\alpha}$) levels were measured in lipopolysaccharide (LPS)-stimulated RAW 264.7 cells. In vivo, We injected MIA $50{\mu}l$ (60 mg/ml) into knee joints of rats to induce osteoarthritis. Rats were divided into total 3 groups (normal, control, BST treated group, each n=7). Normal group was not treated at all without inducing osteoarthritis and taken normal diet. Control group was induced osteoarthritis by MIA and taken with 2 ml of distilled water once a day for 4 weeks. BST treated group was induced osteoarthritis by MIA and taken BST 2 ml (200 mg/kg/mouse) once a day for 4 weeks. We evaluated dynamic weight bearing with the Incapacitance Test Meter. At the end of experiment, the rats were sacrificed to observe the functions of liver and kidney, changes of WBC, neutrophil, lymphocyte, monocyte levels in blood, to evaluate the levels of pro-inflammatory cytokines, tissue inhibitor of metallopreteinases-1 (TIMP-1), matrix metalloproteinase-9 (MMP-9), prostaglandin $E_2$ ($PGE_2$), leukotriene $B_4$ ($LTB_4$) within serum. We observed change of articular structures by Hematoxylin & Eosin (H&E), safranin-O staining method and measured amount of cartilage by micro CT-arthrography. Statistical analysis was done by unpaired student's t-test with significance level at p<0.05 in SPSS 11.0 for windows. Results 1. Safety of the BST was identified. 2. AST, ALT, BUN, creatinine levels of BST treated group were within normal limit. In vitro, 1. DPPH and ABTS free radical scavenging activities of BST showed dose-dependent increase. 2. ROS production were significantly decreased. 3. Total nitric oxide (NO) and IL-$1{\beta}$ production were decreased. 4. IL-6 and TNF-${\alpha}$ production were significantly decreased. In vivo, 1. Weight bearing ability was significantly increased. 2. WBC, neutrophil, lymphocyte, monocyte levels in blood were decreased. 3. IL-$1{\beta}$ and TNF-${\alpha}$ levels in serum were significantly decreased. and the IL-6 level was decreased. 4. TIMP-1, MMP-9, $LTB_4$, $PGE_2$ levels in serum were significantly decreased. 5. Cartilage volume of BST treated group was significantly increased. Also changes of cartilage, synovial membrane, fibrous tissue were suppressed. Conclusions The results obtained in this study Bujasasim-tang have effects of antioxidative, anti-inflammatory, relieve pain and protection of cartilage. Therefore we expect that Bujasasim-tang is effective treatment for osteoarthritis.

Effects of Ohyaksungi-san(Wuyaoshungi-san)and Jungsongouhyul Pharmacopuncture on Pain Reduction and Nerve Regeneration after Crush Injury in Rat Sciatic Nerve (오약순기산(烏藥順氣散) 및 중성어혈(中性瘀血) 약침(藥鍼)이 흰쥐 좌골신경 압좌 손상 후 통증 감소와 신경 재생에 미치는 영향)

  • Jung, Moon-Jae;Lee, Jeong-Han;Yeom, Seung-Ryong;Lee, Su-Kyung;Song, Yung-Sun;Kim, Ki-Byoung;Kwon, Young-Dal
    • Journal of Korean Medicine Rehabilitation
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    • v.19 no.2
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    • pp.51-72
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    • 2009
  • Objectives : This study was designed to evaluate the effects of Ohyaksungi-san(Wuyaoshungi-san) and Jungsongouhyul pharmacopuncture on pain reduction and nerve regeneration after crush injury in rat sciatic nerve. Methods : Animal model was produced through crush injury of right sciatic nerve and they were divided into four groups; Group I: no treatment control group; Group II: experimental group treated with Ohyaksungi-san(Wuyaoshungi-san); Group III: experimental group treated with Jungsongouhyul pharmacopuncture; Group IV: experimental group treated with Ohyaksungi-san(Wuyaoshungi-san) and Jungsongouhyul pharmacopuncture. For the assessment of pain, this study was observed the paw withdrawal latency(PWL) and immunoreactivity on the substance-P. For the assessment of nerve regeneration, the sciatic functional index(SFI) and immunoreactivity on the BDNF were measured. Results : 1. In the assessment of pain, the PWL of experimental groups was significantly higher than control group and group IV was significantly higher than other groups at the all days. 2. In immunohistochemical response of substance-P, as time passes, the immunoreactivity of all groups were decreased gradully. Especially, group IV had the lowest immunoreactivity. 3. In the assessment of SFI, the SFI of experimental groups were significantly higher than control group. 4. In immunohistochemical response of BDNF, the BDNF immunoreactivity of all groups was significantly higher than control group and especially, group IV had the highest immunoreactivity at the 14 days after injury. 5. H & E stain was used on the liver and kidney to investigate toxic effect of Jungsongouhyul pharmacopuncture and Ohyaksungi-san(Wuyaoshungi-san) on on 21 days after injury. However there were no any toxic effects both control group and experimental groups. Conclusions : On the basis of these results, we propose that Ohyaksungi-san(Wuyaoshungi-san) and Jungsongouhyul pharmacopuncture were related to pain reduction and motor nerve recovery, also decreased substance-P expression and increased BDNF expression after crush injury of sciatic nerve, especially these two treatments could be more effective when they were combined simultaneously.

Effect of Black Pepper on the Composition of Serum and Liver in the Rat (호초(胡椒)가 백서(白鼠)의 혈청(血淸) 및 간장성분(肝臟成分)에 미치는 영향(影響))

  • Cho, Soo Yeul;Lee, Sook Hwa
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.12 no.3
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    • pp.219-224
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    • 1983
  • This experiment was undertaken to investigate the effect of black pepper (BP) added to food on a living body and to determine the growth rate, digestibility, weight of organs, composition of blood and liver in the rat. Fifty-six male rats of Sprague-Dawley strain, weight $120{\pm}10g$, were divided into 4 groups and were fed ad libitum for 8 weeks. Experimental diets were divided into 4 groups. Each groups were separately added 0%, 0.5%, 2.0% and 5.0% of BP level. The results obtained are summarized as follows. The highest net weight of liver and heart generally increased according to increasing amount of BP and that of spleen and lung were not significantly different. Kidney weight was significantly higher in the group of containing 5.0% BP. Serum GOT and GPT were not significant, serum glucose was significantly lower in the group of containing 5.0% BP, and serum cholesterol was significantly higher in the group of containing 5.0% BP. Total serum protein decreased gradually as the amount of BP increased, but albumin and globulin were nor affect. Serum Na and K were not significant, but serum Ca and P were decreased as the amount of BP was increased. Liver crude lipid and crude protein were not affect. In fatty acid composition, arachidonic acid was significantly lower in the group of containing 5.0% BP.

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Anti-inflammation and Anti-oxidation Effects of Gamikyejakjimo-tang Herbal Acupuncture on Pathologic Factor and MIA-induced Osteoarthritis Rat (가미계작지모탕약침(加味桂芍知母湯藥鍼)이 퇴행성관절염 병리인자 및 동물병태 모델에 미치는 영향)

  • Lee, Hyun-Jae;Park, Jung-Oh;Oh, Min-Seok
    • Journal of Korean Medicine Rehabilitation
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    • v.25 no.4
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    • pp.1-20
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    • 2015
  • Objectives This study was intended to clarify the anti-inflammation and anti-oxidation effects of gamikyejakjimo-tang herbal acupuncture (GKHA) for osteoarthritis. Methods Osteoarthritis was induced by injection of MIA into right knee joint cavities of rats. Rats were divided into a total of 4 groups (n=8). The 4 groups were normal group, control group, positive comparison group and expeimental group. Indomethacin and GKHA were medicated for a total of 4 weeks. After that, functions of liver and kidney by AST, ALT, creatinine, BUN, DPPH and ABTS free radical scavenging activity, ROS (reactive oxygen species) production, NO (Total Nitric oxide), IL-$1{\beta}$, IL-6, TNF-${\alpha}$ production, weight changes in the hind legs of MIA-induced osteoarthritis rat, serum PGE2, TIMP-1, MMP-2, MMP-9, LTB4, hs-CRP, and white blood cells, neutrophils, lymphocytes, monocytes were measured. The volume of cartilage was observed by micro CT arthrography. H&E and Safranin-O staining were used to examine the injury of synovial tissue. Results 1. In the hind leg weight bearing measurement, level of weight was increased. 2. AST, ALT, BUN, creatinine were decreased. 3. The production of total white blood cell was decreased, and the production of neutrophils, lymphocytes, monocytes were significantly decreased. 4. The production of NO, PGE2, TIMP-1, MMP-2, MMP-9, LTB4 were significantly decreased, and the production of hs-CRP was also decreased but with no significance. 5. The cartilage volume was significantly increased. 6. In H&E staining and Safranin-O staning, the cartilage cell appeared to be proliferated, and proteoglycans appeared to be increased. Conclusions Based on the results above, Gamikyejakjimo-tang Herbal Acupuncture has anti-oxidation and anti-inflammation effects, which leads to suppressing the underlying causes and the progression of osteoarthritis.

Antioxidative Effect of Pine, Oak, and Lily Pollen Extracts (송화분, 참나무 및 백합화분 추출물의 항산화 효능)

  • Kim, Seok-Joong;Youn, Kwang-Sup;Park, Hee-Sung
    • Korean Journal of Food Science and Technology
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    • v.37 no.5
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    • pp.833-837
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    • 2005
  • Antioxidative activities of pine, oak, and lily pollen extracts were evaluated based on 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical-scavenging ability and inhibition of lipid peroxidation in animal tissues. Each pollen was extracted with 50% ethanol, 100% ethanol or water. DPPH radical-scavenging capacity of 50% ethanol extract ($EC_{50}$ 40.0 mg/mL) of pine pollen was higher than those of water (46.8 mg/mL) and 100% ethanol (131.2 mg/mL) extracts of pollen. Fifty percent ethanol (3,2 mg/mL) was also better than 100% ethanol (4.5 mg/mL) and water (8.3 mg/mL) for extraction of oak pollen. For preparation of lily pollen extracts, 100% ethanol was most effective (14.0 mg/mL), followed by water (18.8 mg/mL) and 50% ethanol (24.0 mg/mL). Oak pollen showed higher DPPH radical-scavenging activity than others. Lipid peroxidation in rat brain homogenate induced by ascorbate-Fe3+-EDTA and rat kidney homogenate were inhibited by water extracts of all pollens in dose-dependent manner. Extracts of oak and lily pollen showed higher lipid peroxidation inhibition than pine pollen extract. Polyphenol content was highest in oak pollen extract $(32.5{\pm}0.7\;{\mu}g/mg\;pollen)$, followed by lily extract $(25.9{\pm}1.4\;{\mu}g/mg\;pollen)$ and pine extract $(9.3{\pm}0.7\;{\mu}g/mg\;pollen)$.

Effects of Fermented Milk Feeding on Aluminum Accumulation in Rat (젖산균 발효유섭취가 흰쥐의 장기내 알루미늄축적 억제효과)

  • Park, Seong-Soo;Kim, Joong-Man;Baek, Seung-Hwa
    • Korean Journal of Food Science and Technology
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    • v.32 no.6
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    • pp.1414-1417
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    • 2000
  • This study was to investigate effects of the supplementation of the different lactic acid bacteria[Streptococcus thermophilus KCTC 2185 culture group(ST), autoclaved Streptococcus thermophilus KCTC 2185 culture(STS), Lactobacillus acidophilus ATCC 4356 culture group(LA) and autoclaved Lactobacillus acidophilus ATCC 4356(LAS)] on suppression of aluminum accumulation in organs of rats fed with the diet containing $250\;{\mu}g/g$ aluminum sulfate for 4 weeks. Amount of aluminum accumulation in the control rat was in order of bone>lung>heart>large intestine>kidney>liver>brain>small intestine. Effects of reduction of aluminum accumulation by feeding of the four difference fermented milk were in order of LA group>LAS group>ST group>STS group. ST and LA both were more effective than STS and LAS. Ultimately fermented milk was useful in reduction of toxication by accumulating of aluminum in vivo.

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