• Title/Summary/Keyword: pentoxifylline

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Cilostazol Decreases Ethanol-Mediated TNFalpha Expression in RAW264.7 Murine Macrophage and in Liver from Binge Drinking Mice

  • Lee, Youn-Ju;Eun, Jong-Ryeol
    • The Korean Journal of Physiology and Pharmacology
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    • v.16 no.2
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    • pp.131-138
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    • 2012
  • Alcoholic hepatitis is a leading cause of liver failure in which the increased production of tumor necrosis factor ${\alpha}$ (TNF${\alpha}$) plays a critical role in progression of alcoholic liver disease. In the present study, we investigated the effects of cilostazol, a selective inhibitor of type III phosphodiesterase on ethanol-mediated TNF${\alpha}$ production in vitro and $in$ $vivo$, and the effect of cilostazol was compared with that of pentoxifylline, which is currently used in clinical trial. RAW264.7 murine macrophages were pretreated with ethanol in the presence or absence of cilostazol then, stimulated with lipopolysacchride (LPS). Cilostazol significantly suppressed the level of LPS-stimulated TNF${\alpha}$ mRNA and protein with a similar degree to that by pentoxifylline. Cilostazol increased the basal AMP- activated protein kinase (AMPK) activity as well as normalized the decreased AMPK by LPS. AICAR, an AMPK activator and db-cAMP also significantly decreased TNF${\alpha}$ production in RAW264.7 cells, but cilostazol did not affect the levels of intracellular cAMP and reactive oxygen species (ROS) production. The $in$ $vivo$ effect of cilostazol was examined using ethanol binge drinking (6 g/kg) mice model. TNF${\alpha}$ mRNA and protein decreased in liver from ethanol gavaged mice compared to that from control mice. Pretreatment of mice with cilostazol or pentoxifylline further reduced the TNF${\alpha}$ production in liver. These results demonstrated that cilostazol effectively decrease the ethanol-mediated TNF${\alpha}$ production both in murine macrophage and in liver from binge drinking mice and AMPK may be responsible for the inhibition of TNF${\alpha}$ production by cilostazol.

Pentoxifylline Induces Lipolysis and Apoptosis of Human Preadipocytes, Keratinocytes and Fibroblasts In Vitro

  • Lee, Il-Kyu;Choi, Yun-Jung;Shim, In-Sop;Kim, Kyung-Soo;Choi, Chang-Jin
    • Biomolecules & Therapeutics
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    • v.18 no.1
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    • pp.56-64
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    • 2010
  • Pentoxifylline (PTX) has been used for the local reduction of fat tissue in the clinical setting. However, its safety and efficacy have not been proven. The aim of this study was to evaluate the effects of PTX on cell lines established from fat tissue. Newly cultured human preadipocytes and adipocytes from subcutaneous abdominal fat in addition to purchased human lung fibroblasts and keratinocytes were treated with PTX at different concentrations. Cell viability was determined using the Cell counting kit (CCK)-8 assay and lipolysis was evaluated using an Elisa kit. DNA fragmentation, Western blot analysis, Hoechst and Propidium Iodide (PI) staining and fluorescence activated cell scanning analysis were performed to confirm apoptosis. The viability of adipocytes, preadipocytes, keratinocytes and fibroblasts was markedly decreased at concentrations of PTX above 20 mM. Apoptosis was induced at concentrations of PTX over 40 mM in all cell lines. Lipolysis was increased by 60% at concentrations of PTX of 20 mM compared to the control. In conclusion, the results of this study showed that 20 mM of PTX induced lipolysis. At concentrations over 20 mM, PTX reduced the viability of all cells studied including: adipocytes, preadipocytes, fibroblasts and keratinocytes, in a non-specific manner.

Effects of Caffeine and Pentoxifylline on Pharmacokinetics of Propentofylline

  • Kwon, Oh-Seung;Kim, Min-Hee;Ryu, Jae-Chun;Chung, Youn-Bok
    • Proceedings of the Korean Society of Applied Pharmacology
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    • 1998.11a
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    • pp.122-122
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    • 1998
  • Propentofylline (PPF), a xanthine derivative, has been reported to be effective for the treatment of both vascular dementia and Alzheimer's disease. The elimination half-life of PPF was ranged from 15 to 45 min in rabbit and human, and PPF was rapidly disappeared from the blood. The objective of this experiment is to investigate whether xanthine analogues have effects on the profile of plasma concentration and metabolism of PPF. Caffeine (50 mg/kg, ip) was treated to Sprague-Dawley rats for consecutive 7 days and PPF was intravenously administered to rats 2 hr after the last dose of caffeine. In the other group, PPF was intravenously administered to rats 1 hr after a single dose of pentoxifylline (50 mg/kg, iv). Control group was treated with saline vehicle for the same period as in treatment groups. Blood was withdrawn at specific time intervals. PPF and one of its metabolite (POH) in plasma were determined by gas chromatography/nitrogen phosphorus detector. Plasma concentrations and pharmacokinetic parameters were compared between groups. The area under the curve (AUC) of PPF in rats treated sub chronically with caffeine was significantly decreased compared to control rats. Caffeine treatment results in a significant increase of total body clearance. The AUC of POH was significantly decreased in the caffeine-treated group. A single dose of pentoxifylline has no effect on the phramacokinetics of PPF. Reduction of the AUCs of PPF and POH both suggests that caffeine may increase the excretion of PPF with no affecting the metabolism of PPF to POH.

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Pentoxifylline treatment of frozen pig sperm affects sperm motility and fetal numbers

  • Baek, Sun Young;Chung, Hak Jae;Hong, Joon Ki;Cho, Eun Seok;Choi, Inchul
    • Korean Journal of Agricultural Science
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    • v.47 no.3
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    • pp.657-665
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    • 2020
  • The objective of this study was to investigate whether supplementation of pentoxifylline (PTX; phosphodiesterase inhibitor) to thawed boar semen improves the post-thaw motility of sperm and affects the efficiency of artificial insemination (AI) and further development. To determine the concentration of PTX for AI, frozen-thawed semen was incubated with 0, 5, 10, and 20 mM PTX in an extender freezing medium, respectively, after thawing. Kinematic properties of sperm were examined with a computer-assisted semen analysis (CASA) system. In addition, viability and mitochondrial activity were also tested by LIVE/DEAD and a MitoTracker kit. There were no significant differences in the kinetic parameters of thawed sperm between control and treatment groups, but overall assessment parameters such as motility and rapid progressive were higher in the 10 mM PTX group. In the viability and mitochondrial assay, there were no significant differences observed in the PTX treatment, compared to the control. For further analysis, artificial inseminations were performed using frozen semen and 10 mM PTX treated cryopreserved semen, respectively. There were no differences in pregnancy rates and fetus weights among the groups until 30 and 40 days, but litter size was reduced and relatively low-birth weight was observed in the PTX group. In summary, our findings suggest that enhancement of in vitro sperm quality or non-toxicity supplemented by PTX may have detrimental effects on fetus development.

Effect of Antioxidant Preservative on Cold Protection Ability of Low Grade Riverine Buffalo (Bubalus bubalis) Bull Spermatozoa

  • Pankaj, Prabhat Kumar;Raina, V.S.;Roy, B.;Mohanty, T.K.;Mishra, A.
    • Asian-Australasian Journal of Animal Sciences
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    • v.22 no.5
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    • pp.626-635
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    • 2009
  • An experiment was conducted to investigate the effect of Butylated Hydroxy Anisole (BHA), Butylated Hydroxy Toluene (BHT), Pentoxifylline (PTX), Theophylline (TPY) and Theobromine (TBR) on cold protection ability of Murrah buffalo semen at room ($22-25^{\circ}C$) and refrigerated temperature ($4-7^{\circ}C$). Each semen sample was divided into six parts of equal volume and sperm concentration; the first was kept as a control and the remaining five were treated with BHA, BHT, PTX, TPY or TBR. Sperm motility, abnormal spermatozoa, live-dead count, hypo-osmotic swelling and acrosomal integrity were studied at room and refrigerated temperature for various incubation periods viz.; 0, 4, 8, 12 and 24 h at room and 0, 12, 24, 36, 48, 60 and 72 h at refrigerated temperature. Significant improvement in sperm motility, live-dead count, hypo-osmotic swelling and acrosomal integrity were observed in BHT, PTX and TPY fortified extender at room and refrigerated temperature for various incubation periods. From the present study it could be concluded that cold protection ability of buffalo semen can be improved through the addition of BHT followed by PTX and TPY.

Modification of Late Radiation Response of Rat Salivary Glands by Pentoxifylline and Diltiazem (쥐의 타액선 방사선조사 후 만성반응에 Pentoxifylline과 Diltiazem이 미치는 영향)

  • Suh, Hyun-Suk;Yang, Kwang-Mo;Kang, Yun-Kyung
    • Radiation Oncology Journal
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    • v.17 no.3
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    • pp.230-237
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    • 1999
  • Purpose : To elucidate the effects of pentoxifylline and diltiazem on the late response of the salivary glands of the rat after irradiation. Materials and Methods : Sixteen Sprague-Dawley rats were divided into 4 groups : (a) irradiation alone (b) irradiation with pentixifylline (PTX) (c) irradiation with diltiazem (DTZ) (d) irradiation with both PTX and DTZ. Irradiation was given in a single fraction of 16 Gy using 4 MV photon energy through an anterior port encompassing the left side of the salivary gland leaving the right side of salivary gland as a control. PTX, 20 mg/kg and/or DTZ, 50 mg/kg were infused intraperitoneally before irradiation, Two rats from each group were sacrificed on the 10th week and the rest was sacrificed on the 16th week after irradiation. Histopathologic examinations were undertaken for each section and the proportion of vacuolated cells out of the total number of cells under light microscopic fields was calculated. The statistical significance in the difference of the proportion of the vacuolated cells among the experimental groups was evaluated by a $x^2$-test. Results : Irradiated salivary glands of the 10th week group revealed markedly increased number of vacuolated cells compared to those of unirradiated control. The proportion of vacuolated cells was significantly reduced in both the PTX group (p value=0.001) and the combined PTX and DTX group compared to those of irradiation alone group. The DTZ alone group did not reveal the significant reduction of vacuolated cells compared to those of irradiation alone group (p value, >0.05). The 16th week groups revealed similar findings to those of the 10th week group, but the degree of chronic inflammatory cell infiltrates and interstitial fibrosis was increased and the number of acinar cells was reduced compared to those of the 10th week group. Conclusions : PTX significantly reduced the late radiation response of salivary glands, but DTZ did not reduce the same degree as PTX did. Taking the positive results of this study into consideration, it seems reasonable to apply PTX into the clinical trial for the head and neck irradiation to reduce the late radiation sequelae of salivary glands in the near future. At the same time the further experiment to clarify the subcellar mechni는 involved in PTX should be preceded.

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The effects of pentoxifylline and tocopherol in jaw osteomyelitis

  • Seo, Mi Hyun;Eo, Mi Young;Myoung, Hoon;Kim, Soung Min;Lee, Jong Ho
    • Journal of the Korean Association of Oral and Maxillofacial Surgeons
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    • v.46 no.1
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    • pp.19-27
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    • 2020
  • Objectives: Pentoxifylline (PTX) is a methylxanthine derivative that has been implicated in the pathogenesis of peripheral vessel disease and intermittent lameness. The purpose of this study was to investigate the effect of PTX and tocopherol in patients diagnosed with osteoradionecrosis (ORN), bisphosphonate-related osteonecrosis of the jaw (BRONJ), and chronic osteomyelitis using digital panoramic radiographs. Materials and Methods: This study was performed in 25 patients who were prescribed PTX and tocopherol for treatment of ORN, BRONJ, and chronic osteomyelitis between January 2014 and May 2018 in Seoul National University Dental Hospital. Radiographic densities of the dental panorama were compared prior to starting PTX and tocopherol, at 3 months, and at 6 months after prescription. Radiographic densities were measured using Adobe Photoshop CS6 (Adobe System Inc., USA). Blood sample tests showing the degree of inflammation at the initial visit were considered the baseline and compared with results after 3 to 6 months. Statistical analysis was performed using the Mann-Whitney test and repeated measurement ANOVA using IBM SPSS 23.0 (IBM Corp., USA). Results: Eight patients were diagnosed with ORN, nine patients with BRONJ, and the other 8 patients with chronic osteomyelitis. Ten of the 25 patients were men, average age was 66.32±14.39 years, and average duration of medication was 151.8±80.65 days (range, 56-315 days). Statistically significant increases were observed in the changes between 3 and 6 months after prescription (P<0.05). There was no significant difference between ORN, BRONJ, and chronic osteomyelitis. Only erythrocyte sedimentation rate (ESR) was statistically significantly lower than before treatment (P<0.05) among the white blood cell (WBC), ESR, and absolute neutrophil count (ANC). Conclusion: Long-term use of PTX and tocopherol can be an auxiliary method in the treatment of ORN, BRONJ, or chronic osteomyelitis in jaw.