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Asian Pacific Journal of Cancer... Sep 2019Objective: Pentoxifylline enhances neurite elongation in PC12 cells. This study investigated the effects of pentoxifylline on staurosporine-induced neurite elongation in...
Objective: Pentoxifylline enhances neurite elongation in PC12 cells. This study investigated the effects of pentoxifylline on staurosporine-induced neurite elongation in PC12 cells. Materials and Methods: There were five treatment groups, including treatment group I (1 nM), treatment group II (10 nM), treatment group III (100 nM), treatment group IV (1uM), and treatment group V (10 mM of pentoxifylline), together with 214 nM staurosporine for a range of time (6, 12 and 24 hours). Cells only treated with staurosporine at a concentration of 214 nM were used as the control group. Cell proliferation, cell death, immunocytochemistry assay, and Total Neurite Length were assessed. Results: The results showed that pentoxifylline increased cell viability (p<0.05) in a dose- and time-dependent manner, and cell death assay showed that cell death decreased in a dose- and time-dependent manner (p<0.05). TNL increased significantly compared with control cells (p<0.05). Immunocytochemistry assay showed that pentoxifylline at low and high concentrations enhanced β-tubulin III and GFAP protein expression compared with control cells. Conclusion: It can be concluded that pentoxifylline has positive effects on the staurosporine-induced neurite outgrowth process in PC12 cells.
Topics: Animals; Cell Differentiation; Cell Survival; Enzyme Inhibitors; Humans; Mesenchymal Stem Cells; Neurites; PC12 Cells; Pentoxifylline; Phosphodiesterase Inhibitors; Rats; Signal Transduction; Staurosporine
PubMed: 31554357
DOI: 10.31557/APJCP.2019.20.9.2633 -
Kidney360 Apr 2020Diabetic kidney disease (DKD) is the most common cause of ESKD in the United States and worldwide. Current treatment for DKD includes strict glycemic control and... (Review)
Review
Diabetic kidney disease (DKD) is the most common cause of ESKD in the United States and worldwide. Current treatment for DKD includes strict glycemic control and normalization of BP with renin-angiotensin-aldosterone system (RAAS) blockade. Although RAAS blockers slow progression of disease, they do not generally prevent ESKD and none of the studies with these agents in DKD included patients who were nonproteinuric, which make up an increasingly large percentage of patients with diabetes now seen in clinical practice. Recent studies with glucagon-like peptide-1 receptor agonists and sodium-glucose cotransporter-2 (SGLT2) inhibitors have shown beneficial renal effects, and the benefits of SGLT2 inhibitors likely extend to patients who are nonproteinuric. However, there remains a need to develop new therapies for DKD, particularly in those patients with advanced disease. A role of chronic low-grade inflammation in microvascular complications in patients with diabetes has now been widely accepted. Large clinical trials are being carried out with experimental agents such as bardoxolone and selonsertib that target inflammation and oxidative stress. The Food and Drug Administration-approved, nonspecific phosphodiesterase inhibitor pentoxifylline (PTX) has been shown to have anti-inflammatory effects in both animal and human studies by inhibiting the production of proinflammatory cytokines. Small randomized clinical trials and meta-analyses indicate that PTX may have therapeutic benefits in DKD, raising the possibility that a clinically available drug may be able to be repurposed to treat this disease. A large, multicenter, randomized clinical trial to determine whether this agent can decrease time to ESKD or death is currently being conducted, but results will not be available for several years. At this time, the combination of RAAS blockade plus SGLT2 inhibition is considered standard of care for DKD, but it may be reasonable for clinicians to consider addition of PTX in patients whose disease continues to progress despite optimization of current standard-of-care therapies.
Topics: Animals; Diabetes Mellitus; Diabetic Nephropathies; Humans; Inflammation; Multicenter Studies as Topic; Oleanolic Acid; Pentoxifylline; Randomized Controlled Trials as Topic; Sodium-Glucose Transporter 2 Inhibitors
PubMed: 35372914
DOI: 10.34067/KID.0001252019 -
American Journal of Veterinary Research Jul 2019To determine the pharmacokinetics of pentoxifylline (PTX) and its 5-hydroxyhexyl metabolite (M-I) after IV administration of increasing doses of PTX to sheep.
OBJECTIVE
To determine the pharmacokinetics of pentoxifylline (PTX) and its 5-hydroxyhexyl metabolite (M-I) after IV administration of increasing doses of PTX to sheep.
ANIMALS
6 healthy adult Merino sheep.
PROCEDURES
Each sheep received 10-, 20-, and 40-mg/kg doses of PTX, IV, with a 15-day washout period between doses. Blood samples were collected before and at predetermined times after administration of each dose to determine plasma PTX and M-I concentrations by high-performance liquid chromatography. Pharmacokinetic parameters for PTX and M-I were estimated by noncompartmental analysis.
RESULTS
No adverse effects were observed after administration of the 10- and 20-mg/kg doses. Following administration of the 40-mg/kg dose, all sheep developed tachycardia and hypersalivation and appeared agitated for approximately 4 hours. Plasma PTX concentrations considered therapeutic in other species were achieved in all sheep after administration of all 3 doses. Pharmacokinetic parameters for PTX and M-I varied in a dose-dependent linear manner. For PTX, the mean area under the concentration-time curve (AUC), elimination half-life, and volume of distribution increased with dose and ranged from 15.67 to 94.66 h·μg/mL, 0.68 to 0.91 hours, and 0.55 to 0.66 L/kg, respectively, whereas clearance decreased with dose and ranged from 0.42 to 0.64 L/h/kg. The mean ratio of the AUC for M-I to AUC for PTX ranged from 0.38 to 0.46.
CONCLUSIONS AND CLINICAL RELEVANCE
Results indicated that pharmacokinetic parameters for PTX and M-I varied in a dose-dependent linear manner in healthy sheep. Further studies are warranted to determine the therapeutic threshold and optimal dosage for PTX in sheep.
Topics: Administration, Intravenous; Animals; Area Under Curve; Chromatography, High Pressure Liquid; Cross-Over Studies; Dose-Response Relationship, Drug; Half-Life; Pentoxifylline; Platelet Aggregation Inhibitors; Random Allocation; Sheep
PubMed: 31246127
DOI: 10.2460/ajvr.80.7.702 -
Poultry Science Sep 2022Oxidative stress is associated with impaired sperm quality after thawing. Since mitochondria are the main source of reactive oxygen species (ROS) in sperm, the aim of...
Comparison of the performance of targeted mitochondrial antioxidant mitoquinone and non-targeted antioxidant pentoxifylline in improving rooster sperm parameters during freezing and thawing.
Oxidative stress is associated with impaired sperm quality after thawing. Since mitochondria are the main source of reactive oxygen species (ROS) in sperm, the aim of this study was to investigate the effects of targeted mitochondrial antioxidant mitoquinone (MitoQ) and non-targeted mitochondrial antioxidant pentoxifylline (PTX) during cooling and cryopreservation of rooster sperm. Sperm samples were collected from 15 roosters aged 28 wk and diluted with Beltsville extender. After dilution and addition of treatments (50, 100, and 200 pMol MitoQ and 0.5, 0.75, and 1 μM PTX), samples were cooled for 2 h to 4°C and they were first analyzed at this stage and were frozen and re-evaluated after thawing. After the freezing and thawing, level of 100 pMol MitoQ significantly increased total motility (TM), progressive motility (PGM), curvilinear velocity (VCL), membrane integrity, viability, total antioxidant capacity (TAC) and the glutathione peroxidase (GPx), as well as the level of 50 pMol significantly increased TM, PGM, average path velocity (VAP), straight-line velocity (VSL), membrane integrity, viability, and mitochondrial activity. Moreover, these 2 levels (50 and 100 PMol) decreased malondialdehyde and sperm with abnormal morphology. Addition of 0.75 μM PTX also increased total motility compared to the control group and levels of 0.5 and 0.75 μM decreased sperm with abnormal morphology. It could be concluded the addition of MitoQ and PTX can be useful for sperm cryopreservation industry and reduce the harmful effects of freeze-thawing.
Topics: Animals; Antioxidants; Chickens; Cryopreservation; Cryoprotective Agents; Freezing; Male; Mitochondria; Organophosphorus Compounds; Pentoxifylline; Semen; Semen Analysis; Semen Preservation; Sperm Motility; Spermatozoa; Ubiquinone
PubMed: 35917673
DOI: 10.1016/j.psj.2022.102035 -
American Family Physician May 2017
Topics: Age Factors; Compression Bandages; Humans; Leg Ulcer; Pentoxifylline; Platelet Aggregation Inhibitors; Quality of Life; United Kingdom; Varicose Ulcer
PubMed: 28671410
DOI: No ID Found -
The European Respiratory Journal Aug 1994
Topics: Animals; Hyperoxia; Pentoxifylline; Respiratory Distress Syndrome; Tumor Necrosis Factor-alpha
PubMed: 7957822
DOI: 10.1183/09031936.94.07081389 -
Acta Cirurgica Brasileira 2020To assess the action of pentoxifylline, administered by subcutaneous route, on skin flap tissue repair in rats, and to verify the histological aspects and biomarkers.
PURPOSE
To assess the action of pentoxifylline, administered by subcutaneous route, on skin flap tissue repair in rats, and to verify the histological aspects and biomarkers.
METHODS
Thirty-two male Wistar rats were divided into four groups: control (CT) and treated with pentoxifylline (P1, P3 and P5). Modified McFarlane technique flap was used. Ten days later, the animals were euthanized and the areas of viable and necrotic tissue were evaluated. Hematoxylin/eosin staining was used to assess the morphometric characteristics of the number of vessels and epithelial thickness. Picrosirius red was used to assess collagen density. VEGF and TGF-?1 levels on the skin flap and serum of the animals were measured by the ELISA method.
RESULTS
The macroscopic evaluation of the skin flap dimensions showed reduced necrotic tissue in the pentoxifylline (p < 0.05) treated groups. There was an increase in angiogenesis and reepithelization, demonstrated by analyses with an increased number of vessels (p < 0.05), VEGF and epithelial thickness. Fibrogenic effect showed decreased collagen density and TGF-β1 in the skin flap and serum.
CONCLUSION
The benefits of pentoxifylline administered by subcutaneous route, at dose 100 mg/kg, which was effective to improve the survival of skin flap by acting on tissue repair components, stimulating angiogenesis and reepithelization, in addition to reducing fibrogenesis.
Topics: Animals; Graft Survival; Male; Necrosis; Pentoxifylline; Rats; Rats, Wistar; Skin Transplantation; Surgical Flaps
PubMed: 33331455
DOI: 10.1590/ACB351105 -
Life Sciences Oct 2020The pharmacological properties of pentoxifylline have been re-evaluated, particularly in chronic kidney disease in diabetes, favored by its anti-inflammatory action....
AIM
The pharmacological properties of pentoxifylline have been re-evaluated, particularly in chronic kidney disease in diabetes, favored by its anti-inflammatory action. Definitive evidences of renal outcomes are lacking, which indicates the need for investigation of novel mechanisms of action of pentoxifylline. We postulated that components associated with the metabolism of advanced glycation end products (AGEs) may be modulated by pentoxifylline, which consequently decreases the detrimental effects of obesity on kidneys.
MAIN METHODS
C57BL-6J mice were fed a high-fat diet for 14 weeks and treated with 50 mg/kg pentoxifylline during the last 7 weeks. Changes in the renal levels of AGE metabolism-associated components were investigated, with particular focus on the receptor for AGEs (RAGE), its downstream components, and components related to AGE detoxification, including glyoxalase 1 (GLO 1).
KEY FINDINGS
Pentoxifylline reduced body weight gain, improved insulin sensitivity and glucose tolerance, downregulated biomarkers of glycoxidative stress, and enhanced plasma paraoxonase 1 activity. In the kidneys, pentoxifylline inhibited glomerular expansion, lipid deposition, reduced pro-inflammatory cytokine levels, and induced the activation of AMP-activated protein kinase. Pentoxifylline inhibited the renal accumulation of AGEs and reduced the levels of RAGE and its downstream components, and consequently mitigated oxidative stress and apoptosis. Pentoxifylline also increased the renal levels of GLO 1 and the activities of antioxidant enzymes. Urinary albumin levels were observed to be lowered, which reconfirmed the antialbuminuric effects of pentoxifylline.
SIGNIFICANCE
The novel mechanisms of action help explain the renoprotective effects of pentoxifylline and the attenuation of obesity-associated renal complications related to glycoxidative stress.
Topics: Animals; Glycation End Products, Advanced; Glycolysis; Kidney; Lactoylglutathione Lyase; Mice, Obese; Oxidative Stress; Pentoxifylline; Receptor for Advanced Glycation End Products; Signal Transduction
PubMed: 32763295
DOI: 10.1016/j.lfs.2020.118196 -
European Review For Medical and... May 2022This systematic review and meta-analysis aimed to synthesize the latest evidence on pentoxifylline effect on the contrast-induced nephropathy (CIN) and whether the... (Meta-Analysis)
Meta-Analysis
The role of pentoxifylline in preventing contrast-induced nephropathy in coronary angiography/intervention - systematic review, meta-analysis, and meta-regression of randomized controlled trials.
OBJECTIVE
This systematic review and meta-analysis aimed to synthesize the latest evidence on pentoxifylline effect on the contrast-induced nephropathy (CIN) and whether the quality evidence is sufficient to make a definite conclusion MATERIALS AND METHODS: We performed a systematic literature search on topics that assesses pentoxifylline and CIN in coronary angiography/intervention up until 01 April 2021 using PubMed, Scopus, Embase, and hand-sampling. Primary outcome was CIN defined as ≥0.5 mg/dL or 25% rise in the SCr 48 h after procedure.
RESULTS
There were a total of 1142 subjects from 6 studies. There was no difference between pentoxifylline and control group in terms of serum creatinine at baseline (p=0.46) and after the procedure (p=0.33). The incidence of CIN was 51/571 (8.9%) in the pentoxifylline group and 61/571 (10.7%) in the control group. Pentoxifylline was not significantly associated with increase or decrease in the risk of CIN (RR 0.84 [0.59, 1.19], p=0.32; I2: 0%, p=0.89). Subgroup analysis for elective studies showed a non-significant result (RR 0.77 [0.47, 1.27], p=0.31; I2: 0%). Meta-regression analysis showed that the association between pentoxifylline and mortality was not affected by age (p=0.994), gender (reference: male, p=0.562), hypertension (p=0.336), diabetes (p=0.536), baseline serum creatinine (p=0.344), contrast used (p=0.431), and CIN incidence (p=0.521). GRADE Approach showed a low certainty of evidence for the effect estimate of pentoxifylline on CIN.
CONCLUSIONS
Our meta-analysis showed that pentoxifylline was not associated with the risk of CIN with low certainty of evidence. Hence, larger, multicentre, double-blind randomized controlled trials are required.
Topics: Contrast Media; Coronary Angiography; Creatinine; Humans; Kidney Diseases; Male; Pentoxifylline; Randomized Controlled Trials as Topic
PubMed: 35587083
DOI: 10.26355/eurrev_202205_28750 -
World Journal of Gastroenterology Sep 2012To determine the effects of pentoxifylline (PTX) on clinical manifestations and evaluate arterial blood gas data in hepatopulmonary syndrome (HPS) in children.
AIM
To determine the effects of pentoxifylline (PTX) on clinical manifestations and evaluate arterial blood gas data in hepatopulmonary syndrome (HPS) in children.
METHODS
In a pilot study of 10 children with chronic liver disease, who had HPS, 20 mg/kg/d PTX was administered for 3 mo. Clinical data and arterial blood gas parameters were evaluated at baseline, the end of the treatment period, and 3 mo after drug discontinuation.
RESULTS
Six patients could tolerate PTX, while four patients experienced complications. Among patients who could tolerate PTX, there was a significant increase in arterial oxygen pressure (PaO(2)) (P = 0.02) and oxygen saturation (SaO(2)) (P = 0.04) and alveolar-arterial oxygen gradient (P = 0.02) after 3 mo of treatment. Significant decreases in PaO(2) (P = 0.02) and alveolar-arterial oxygen gradient (P = 0.02) were also seen after drug discontinuation.
CONCLUSION
PTX may improve PaO(2), SaO(2) and alveolar-arterial oxygen gradient in the early stage of HPS.
Topics: Adolescent; Blood Gas Analysis; Child; Child, Preschool; Female; Hepatopulmonary Syndrome; Humans; Male; Oxygen; Pentoxifylline; Phosphodiesterase 4 Inhibitors; Pilot Projects; Pulmonary Alveoli; Time Factors; Treatment Outcome
PubMed: 23002364
DOI: 10.3748/wjg.v18.i35.4912