• Title/Summary/Keyword: Sodium salicylate

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Sodium Salicylate Induces the Cyclin-dependent Kinase Inhibitor p21 (Waf1/Cip1) through PI3K-related Protein Kinase-dependent p53 Activation in A549 Cells

  • Kim, Min-Young;Kim, Cho-Hee;Hwang, Jee-Won;Kim, Ji-Hye;Park, Hye-Gyeong;Kang, Ho-Sung
    • Biomedical Science Letters
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    • v.13 no.2
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    • pp.75-81
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    • 2007
  • Sodium salicylate (NaSal), a chemopreventive drug, has been shown to induce apoptosis and cell circle arrest depending on its concentrations in a variety of cancer cells. In A549 cells, low concentration of NaSal (5$\sim$10 mM) induces cell cycle arrest, whereas it induces apoptosis at higher concentration of 20 mM. In the present study, we examined the molecular mechanism for NaSal-induced cell cycle arrest. NaSal induced expression of p53, p21 (Wafl/Cipl), and p27 (Kipl) that play important roles in cell cycle arrest. p53 induction was mediated by its phosphorylation at Ser-15 that could be prevented by the PI3K-related kinase (ATM, ATR and DNA-PK) inhibitors including wortmannin, caffeine and LY294002. In addition, NaSal-induction of p2l (Wafl/Cipl) was detected in P53 (+/+) wild type A549 cells but not in p53 (-/-) mutant H1299 cells, indicating p53-dependent p21 (Wafl/Cipl) induction. In contrast, p27 (Kipl) that is a negative regulate. of cell cycle with p21 (Wafl/Cipl) was observed both in A549 cells and H1299 cells. Thus, 5 mM NaSal appeared to cause cell cycle arrest through inducing the cyclin-dependent kinase inhibitor p21 (Wafl/Cipl) via PI3K-related protein kinase-dependent p53 activation as well as by up-regulating p27 (Kipl) independently of p53 in A549 cells.

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Antioxidant activity and metabolic regulation of sodium salicylate on goat sperm at low temperature

  • Wenzheng Shen;Yu Fu;Haiyu Bai;Zhiyu Zhang;Zhikun Cao;Zibo Liu;Chao Yang;Shixin Sun;Lei Wang;Chunhuan Ren;Yinghui Ling;Zijun Zhang;Hongguo Cao
    • Animal Bioscience
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    • v.37 no.4
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    • pp.640-654
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    • 2024
  • Objective: The purpose of this study was to explore the effect of sodium salicylate (SS) on semen preservation and metabolic regulation in goats. Methods: Under the condition of low temperature, SS was added to goat semen diluent to detect goat sperm motility, plasma membrane, acrosome, antioxidant capacity, mitochondrial membrane potential (MMP) and metabonomics. Results: The results show that at the 8th day of low-temperature storage, the sperm motility of the 20 μM SS group was 66.64%, and the integrity rates of the plasma membrane and acrosome were both above 60%, significantly higher than those of the other groups. The activities of catalase and superoxide dismutase in the sperm of the 20 μM SS group were significantly higher than those of the control group, the contents of reactive oxygen species and malondialdehyde were significantly lower than those in the control group, the MMP was significantly higher than that in the control group, and the contents of Ca2+ and total cholesterol were significantly higher than those in the control group. Through metabonomics analysis, there were significant metabolic differences between the control group and the 20 μM SS group. Twenty of the most significant metabolic markers were screened, mainly involving five metabolic pathways, of which nicotinic acid and nicotinamide metabolic pathways were the most significant. Conclusion: The results indicate that SS can effectively improve the low-temperature preservation quality of goat sperm.

A Study on the Absorption Enhancing Effect of Sodium 5-Methoxysalicylate(II) (Sodium 5-Methoxy Salicylate의 흡수촉진 효과에 관한 연구 (II). 흡수촉진제에 대한 반응성)

  • 김기헌
    • YAKHAK HOEJI
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    • v.30 no.2
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    • pp.96-99
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    • 1986
  • Absorption enhancing effect of 5 MSA-Na at the mucous memberanes of the rectum and duodenum was studied via in vitro sac test. There were no significant differences between two membranes. Effect of 5MSA-Na on the transfer of CMZ to the tissue was also studied via in situ loop method. There was no significant difference at the duodenum, compared to the control when CMZ was administered intravenously. Transfer of CMZ to the loop of the rectum was increased in the presence of 5MSA-Na compared to the control, which might be attributed to the enhanced permeability of the mucous memberane of the rectum.

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Dual Drug-Loaded Liposomes for Synergistic Efficacy in MCF-7 Breast Cancer Cells and Cancer Stem Cells

  • Park, Hee-Bin;Kim, Yun-Ji;Lee, Seong-Min;Park, James S.;Kim, Keun-Sik
    • Biomedical Science Letters
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    • v.25 no.2
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    • pp.159-169
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    • 2019
  • Breast cancer stem cells (BCSCs) in breast cancer cells have self-renewal ability and differentiation potential. They are also resistant to drugs after chemotherapy. To overcome this resistance, we designed negatively charged 1,2-dimyristoyl-sn-glycero-3-phosphoglycerol (DMPG)-based liposomes for drug delivery. These liposomes have enhanced the therapeutic effects of a range of antitumor therapies by increasing the cellular uptake and improving drug delivery to targets sites. In this study, we investigated whether DMPG-POPC liposomes, including the neutral lipid 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholin (POPC), can specifically bind to MCF-7 breast cancer cells and increase cellular uptake compared with that by CHOL-POPC liposomes. We also estimated the cytotoxicity of DMPG-POPC liposomes encapsulated with both metformin (Met) and sodium salicylate (Sod) against breast cancer cells and BCSCs compared with that of the free drugs. Our results demonstrated that these dual drug-encapsulated liposomes significantly enhanced the cytotoxic and anti-colony formation abilities compared with individual drug-encapsulated liposomes or free drugs in BCSCs. Overall, our results suggest that DMPG-POPC liposomes containing two drugs (Met + Sod) show promise for synergistic anti-cancer therapy of breast cancer by increasing drug delivery efficiency into breast cancer cells and BCSCs.

The Role of Excipients in Iontophoretic Drug Delivery: In vitro Iontophoresis of Isopropamide and Pyridostigmine through Rat Skin and Effect of Ion-pair Formation with Organic Anions

  • Shim, Chang-Koo
    • Journal of Pharmaceutical Investigation
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    • v.23 no.3
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    • pp.41-50
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    • 1993
  • The iontophoretic delivery across rat skin of quaternary ammonium salts (isopropamide: ISP, pyridostigmine: PS), which are positively charged over a wide pH range, was measured ill vitro. The study showed that: (a) iontophoresis significantly enhanced delivery of ISP and PS compared to respective passive transport; (b) delivery of ISP and PS was directly proportional to the applied continuous direct current density over the range of $0-0.69\;mA/cm^2;$ (c) delivery of ISP and PS was also proportional to the drug concentration in the donor compartment over the range of $0-2{\time}l0^{-2}M:$ (d) sodium ion in the donor compartment inhibited the drug transport possibly due to decreasing the electric transference number of the drug; (e) delivery of ISP and PS increased as the pH of the donor solution increased over the pH range 2-7 suggesting permselective nature of the epidermis, and inhibition of the transference number of the drugs by hydronium ion; (f) some organic anions such as taurodeoxycholate, salicylate and benzoate which form lipophilic ion-pair complexes with ISP inhibited the delivery of ISP. The degree of inhibition by the organic anions was linearly proportional to the extraction coefficient $(K_e)$ of ISP from the partition system with each counteranion between phosphate buffer (pH 7.4) and n-octanol. For PS, however, taurodeoxycholate, but not salicylate and benzoate inhibited the iontophoretic delivery. It suggests that not only sodium ion and hydronium ion but also the counteranions which form lipophilic ion-pairs with quaternary ammonium drugs are not favorable components in formulating the donor solution of the drugs to achieve an effective iontophoretic delivery.

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Mechanism for Chemiluminescent Reactions of Bis(2,4,6-trichlorophenyl)oxalate, Hydrogen Peroxide and Fluorescent Aromatic Hydrocarbons

  • Song Hyung-Soo;Shin Hyung Seon;Kim Kang-Jin
    • Bulletin of the Korean Chemical Society
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    • v.9 no.1
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    • pp.17-21
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    • 1988
  • A mechanistic study on the chemiluminescence resulting from the reaction between bis(2,4,6-trichlorophenyl)oxalate(TCPO) and hydrogen peroxide in the presence of fluorescent polycyclic aromatic hydrocarbons in a viscous phthalate medium has been conducted. The rate determining step, decay rate constants, and relative quantum efficiencies yielded by varying the concentration of reagents generally support an existing mechanism. However, a reaction between TCPO and sodium salicylate was not observed.

Preparation of Polycaprolactone Microcapsules by Membrane Emulsification Method and Its Drug Release Properties (막유화법에 의한 생분해성 Polycaprolactone 마이크로캡슐의 제조와 약물방출 특성)

  • Youm, Kyung-Ho;Yun, Tae-Ho;Kim, Kong-Soo;Cho, Suh-Hyeong
    • Membrane Journal
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    • v.17 no.1
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    • pp.67-79
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    • 2007
  • Uniform microcapsules containing ionic model drugs were prepared by controlling various conditions of emulsification procedure using a lab-scale membrane emulsification system with a SPG (Shirasu porous glass) tubular membrane. We observed the effects of various emulsification parameters [concentration and molecular weight of polycaprolatone (PCL) polymer, transmembrane pressure and emulsifier concentration in disperse phase and continuous phase, stirring speed] on the mean size and size ditribution of microcapsules containing lidocaine hydrochloride (cationic drug), sodium salicylate (nonionic drug) and 4-acetaminophen (anionic drug) used as a model drugs. Also, release characteristics of a model drugs from PCL microcapsules were investigated. Controlling membrane emulsification parameters, uniform PCL microcapsules with about $5\;{\mu}m$ of the mean size were finally prepared. The release rate and the burst effect of microcapsules were decreased in condition of the acidic solution, but it was increased in condition of the base solution.

Prediction of the Concentration of Diphenylhydantion in the Brain Using a Physiological Pharmacokinetic Hybrid Model

  • Song, Sae-Heum;Shim, Chang-Koo;Lee, Min-Hwa;Kim, Shin-Keun
    • Archives of Pharmacal Research
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    • v.13 no.3
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    • pp.221-226
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    • 1990
  • A physiological pharmacokinetic hybrid model was developed in order to predict the disposition kinetics of diphenylhydantoin (DPH) in the brain from the plasma conentration data of DPH. The model was constructed under the assumptions of well-stirred, plasma flow-limited and lienar tissue diposition kinetics of DPH. DPH was administered intravenously to the rats at a dose of 10 mg/kg together with/without sodium salicylate (SA;10 mg/kg) and the DPH concentrations in the plasma and brain were determined. Plasma protein binding of DPH concentrations in the plasma and brain were determined. Plasma protein binding of DPH was also determined using equilibrium dialysis technique. Then the model was tested for its predictability of DPH concentrations in the brian from the plasma data of DPH. It was found that the predicted values of DPH concentrations in the brian were in fair agreement with the experimental values in the rats of both treatments. The 2-fold increase in the brain concentration of DPH by SA-coadinistration was predicted well from the plasma concentration and plasma free fraction ($f_p$) data of DPH using the model. Therefore, the hybrid model was concluded to be very useful for the prediction of the concentrations of DPH in the brain from the plasma concentration data. Finally, DPH concentrations in the human brian was calculated using this model from plasma DPH data in the literature, yet the scale-up of this model to the human is not convinced.

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Dissolution Characteristics of Biphenyl Dimethyl Dicarboxylate from Solid Dispersions with Copolyvidone

  • Moon, Jee-Hyun;Chun, In-Koo
    • Proceedings of the Korean Society of Applied Pharmacology
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    • 1997.04a
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    • pp.118-118
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    • 1997
  • Solid dispersions were used to increase the dissolution rate of biphenyl dimethyl dicarboxylate (DDB) in water, with the ultimate goal of optimizing its bioavailability when incoporated into pharmaceuticals. Carriers used were Kollidon 30, Kollidon VA 64, 2-hydroxypropyl-${\beta}$-cyclodextrin (HPCD), sodium salicylate or sodium benzoate. DDB solid dispersions were prepared at drug to carrier proportions ranging from 1 : 5 to 1 : 20 (w/w) by solvent evaporation method. DDB tablets (7.5 mg) were prepared by compressing the powder mixture composed of solid dispersions, lactose, corn starch, crospovidone and magnesium stearate using a single-punch press. DDB capsules (7.5 mg) were prepared by filing the mixture into empty hard gelatin capsules (size #1). Dissolution studies of DDB from powdered solid dispersions, tablets and capsules were performed in 900 $m\ell$ of water at 100 rpm and 37$^{\circ}C$ by the paddle method. The dissolved amount was assayed by HPLC and expressed as the mean(%)of three determinations.

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