• Title/Summary/Keyword: fenofibrate

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Activation of $PPAR{\alpha}$ Attenuates $IFNP{\gamma}$ and IL-$1{\beta}$-induced Cell Proliferation in Astrocytes: Involvement of IL-6 Independent Pathway

  • Lee, Jin-Koo;Seo, Eun-Min;Lee, Sang-Soo;Park, Soo-Hyun;Sim, Yun-Beom;Jung, Jun-Suh;Kim, Seon-Mi;Suh, Hong-Won
    • The Korean Journal of Physiology and Pharmacology
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    • v.14 no.3
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    • pp.185-189
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    • 2010
  • The present study demonstrates the effect of fibrates, agonists of $PPAR{\alpha}$ on cytokines-induced proliferation in primary cultured astrocytes. Alone or combination treatment with cytokines, such as IL-$1{\beta}$ (10 ng/ml), $IFNP{\gamma}$ (10 ng/ml), and TNF-$\alpha$ (10 ng/ml) cause a significant increase of cell proliferation in a time-dependent manner. Treatment of astrocytes with bezafibrate and fenofibrate (0, 5, and $10\;{\mu}M$) reduced the $IFNP{\gamma}$ and IL-$1{\beta}$-induced cell proliferation in a dose-dependent manner. To address the involvement of IL-6 on the $IFNP{\gamma}$ and IL-$1{\beta}$-induced cell proliferation, released IL-6 level was measured. $IFNP{\gamma}$ and IL-$1{\beta}$ cause an increase of released IL-6 protein level in a time-dependent manner. Furthermore, pretreatment with IL-6 antibody (0, 0.1, 1, 2.5, and 5 ng/ml) dose-dependently inhibited the $IFNP{\gamma}$ and IL-$1{\beta}$-induced cell proliferation. However, bezafibrate and fenofibrate did not affect increased mRNA and protein levels of IL-6 in $IFNP{\gamma}$ and IL-$1{\beta}$-stimulated astrocytes. Taken together, these results clearly suggest that activation of $PPAR{\alpha}$ attenuates the $IFNP{\gamma}$ and IL-$1{\beta}$-induced cell proliferation through IL-6 independent pathway.

Fenofibrate decreases radiation sensitivity via peroxisome proliferator-activated receptor ${\alpha}$-mediated superoxide dismutase induction in HeLa cells

  • Liu, Xianguang;Jang, Seong-Soon;An, Zhengzhe;Song, Hye-Jin;Kim, Won-Dong;Yu, Jae-Ran;Park, Woo-Yoon
    • Radiation Oncology Journal
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    • v.30 no.2
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    • pp.88-95
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    • 2012
  • Purpose: The fibrates are ligands for peroxisome proliferator-activated receptor (PPAR) ${\alpha}$ and used clinically as hypolipidemic drugs. The fibrates are known to cause peroxisome proliferation, enhance superoxide dismutase (SOD) expression and catalase activity. The antioxidant actions of the fibrates may modify radiation sensitivity. Here, we investigated the change of the radiation sensitivity in two cervix cancer cell lines in combination with fenofibrate (FF). Materials and Methods: Activity and protein expression of SOD were measured according to the concentration of FF. The mRNA expressions were measured by using real time reverse-transcription polymerase chain reaction. Combined cytotoxic effect of FF and radiation was measured by using clonogenic assay. Results: In HeLa cells total SOD activity was increased with increasing FF doses up to 30 ${\mu}M$. In the other hand, the catalase activity was increased a little. As with activity the protein expression of SOD1 and SOD2 was increased with increasing doses of FF. The mRNAs of SOD1, SOD2, $PPAR{\alpha}$ and $PPAR{\gamma}$ were increased with increasing doses of FF. The reactive oxygen species (ROS) produced by radiation was decreased by preincubation with FF. The surviving fractions (SF) by combining FF and radiation was higher than those of radiation alone. In Me180 cells SOD and catalase activity were not increased with FF. Also, the mRNAs of SOD1, SOD2, and $PPAR{\alpha}$ were not increased with FF. However, the mRNA of $PPAR{\gamma}$ was increased with FF. Conclusion: FF can reduce radiation sensitivity by ROS scavenging via SOD induction in HeLa. SOD induction by FF is related with $PPAR{\alpha}$.

Antihyperlipedimic activity of several traditional herbal medicines on experimental hyperlipidemia in rats (고지혈증 랫트를 이용한 수종 전통 한약제의 항고지혈 효과(II))

  • RO Hwan Seong;Ko Woo Kyoung;Kim Ona Ja;Park Kun Koo;Cho Young Hwan;Park Hyungsup
    • Korean Journal of Clinical Pharmacy
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    • v.5 no.2
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    • pp.61-69
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    • 1995
  • Hyperlipidemia is a major predisposing factor of atherosclerosis and cerebrovascular accidents. In effort to develope a hypolipidemic drug from medicinal herb, We tested three prescriptions of traditional medicine for the lipid lowering effect on diet-induced hyperlipidemic rats. GyejI-Bokryung-Hwan, Ohyak-Sunki-San, and Shihoga-Yongol-Moryu-Tang were selected based on the comnon prescriptions for patients with hyperlipidemia-related diseases. Water extract from each prescriptions was made by the method used in the clinical setting, and administered intragastrically once a day, for 4 weeks. Fenofibrate and lovastatin were given by the same method as the control drugs. Blood levels of total cholesterol(TC), high density lipoprotein(HDL), low density lipoprotein (LDL), and triglyceride(TG) were measured before, 1, 2, 3, and 4 weeks after starting the drug administration. All of the traditional prescriptions did not show lipid lowering effect, while fenofibrate lower the blood cholesterol levels(TC;from 215mg/dl before to 182m41 at 4 weeks-point of drug administration, and LDL ;from 203mg/dl before to aut 161, and 163mg/dl at 3 and 4 week-point respectively). Oyak-Sunki-San increased the level of TC (from 283mg/dl to over 350mg/dl starting from the first week of drug administratin). Effects on TG variable in the cases of traditional medicines and control drug In conclusion, any of the three traditional medical prescriptions did not decrease the level of blood cholesterol.

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Biodegradation of Blood Lipid Lower Agents (BLLAs) in Biological Activated Carbon (BAC) Process (BAC 공정에서의 고지혈증 치료제 생물분해 특성)

  • Yoom, Hoon-Sik;Son, Hee-Jong;Ryu, Dong-Choon;Yoo, Pyung-Jong
    • Journal of Korean Society of Environmental Engineers
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    • v.39 no.3
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    • pp.124-131
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    • 2017
  • In this study, We investigated the effects of water temperature and empty bed contact time (EBCT) on the biodegradability of 8 blood lipid lower agents (BLLAs) in biological activated carbon (BAC) process. Experiments were conducted at three water temperatures ($8^{\circ}C$, $16^{\circ}C$ and $24^{\circ}C$) and three EBCTs (5 min, 10 min and 15 min). Increasing water temperature and EBCT increased the biodegradation efficiency of BLLAs in BAC process. Simvastatin and fenofibrate were the highest biodegradation efficiency, but atorvastatin and clofibric acid were the lowest. The kinetic analysis suggested a pseudo-first-order reaction model for biodegradation of 8 BLLAs at various water temperatures and EBCTs. The pseudo-first-order biodegradation rate constants ($k_{bio}$) of clofibric acid and atorvastatin were $0.0075min^{-1}$ and $0.0122min^{-1}$ at $8^{\circ}C$, and were $0.0540min^{-1}$ and $0.0866min^{-1}$ at $24^{\circ}C$, respectively. By increasing the water temperature from $8^{\circ}C$ to $24^{\circ}C$, the biodegradation rate constants ($k_{bio}$) were increased 7.1~7.2 times.

Graphene nanosheets encapsulated poorly soluble drugs with an enhanced dissolution rate

  • Shen, Shou-Cang;Ng, Wai Kiong;Letchmanan, Kumaran;Lim, Ron Tau Yee;Tan, Reginald Beng Hee
    • Carbon letters
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    • v.27
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    • pp.18-25
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    • 2018
  • In this study, graphene oxide(GO) was used as drug carriers to amorphize poorly watersoluble drugs via a co-spray drying process. Two poorly water-soluble drugs, fenofibrate and ibuprofen, were investigated. It was found that the drug molecules could be in the graphene nanosheets in amorphous or nano crystalline forms and thus have a significantly enhanced dissolution rate compared with the counterpart crystalline form. In addition, the dissolution of the amorphous drug enwrapped with the graphene oxide was higher than that of the amorphous drug in activated carbon (AC) even though the AC possessed a larger specific surface area than that of the graphene oxide. The amorphous formulations also remained stable under accelerated storage conditions ($40^{\circ}C$ and 75% relative humidity) for a study period of 14 months. Therefore, graphene oxide could be a potential drug carrier and amorphization agent for poorly water-soluble drugs to enhance their bioavailability.

A Case of Xanthoma Disseminatum with Laryngeal Involvement (후두에 발생한 파종성 황색종 1예)

  • Park, Jin Su;Lee, Young Woo;Lee, Sang Hyuk;Jin, Sung Min
    • Journal of the Korean Society of Laryngology, Phoniatrics and Logopedics
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    • v.26 no.1
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    • pp.58-62
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    • 2015
  • Xanthoma disseminatum (XD) is a benign, non-Langerhans cell histiocytosis characterized by disseminated xanthomatous lesions with face, flexures, and mucosa. Most of XD develops in mucocutaneous lesions including skin, oral cavity and pharynx, however laryngeal involvement is uncommon. While the natural course of XD is usually benign and often self-limiting, but XD develop in critical anatomical locations may result in morbidity and mortality. Localized mucous lesions in oropharynx and larynx lead to dysphagia, dyspnea and air way obstruction. The diagnosis of XD was based on clinical, histological and immunohistochemical findings. The treatment is complex and non-consensual. Local treatment with cryotherapy, radiotherapy, surgery, and carbon dioxide lasers have been attempted with various results. Systemic medication with peroxisome proliferator-activated gamma receptors, statins, fenofibrate, chlorodeoxyadenosine, cyclophosphamide, doxycycline, and cyclosporine have also been reported, but none have proven particularly successful. A 59-year-old man presented with respiratory symptoms because of laryngeal involvement of XD. We had to remove the obstructive lesion for relieving the symptoms. We experienced XD in Larynx that was rare in otorhinolaryngology. So we report this case with review of literatures.

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