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Journal of Pharmacy & Pharmaceutical... 2016To determine if there is sufficient evidence to recommend the addition of pentoxifylline to standard ACE inhibitor and ARB therapy in chronic kidney disease patients to... (Review)
Review
PURPOSE
To determine if there is sufficient evidence to recommend the addition of pentoxifylline to standard ACE inhibitor and ARB therapy in chronic kidney disease patients to reduce proteinuria and preserve kidney function.
METHODS
A search of the literature was conducted using the PubMed.gov and ClinicalTrials.gov search engines and the search terms "pentoxifylline renoprotection", "pentoxifylline CKD", and "pentoxifylline nephropathy". RESULTS were limited to studies in human subjects and published in the English language. No date range was specified. Studies focused on the effects of pentoxifylline on drug induced nephropathy were excluded.
RESULTS
Nine relevant articles were retrieved and evaluated. The two main populations studied were patients with chronic kidney disease (CKD) and patients with CKD and comorbid type 2 diabetes. Six of the nine studies reported a significant reduction in proteinuria in pentoxifylline treated patients. Four studies reported a significant change in estimated glomerular filtration rate (eGFR).
CONCLUSION
Addition of pentoxifylline to ACE inhibitor and ARB therapy may improve proteinuria in CKD patients. There is conflicting evidence as to whether pentoxifylline will improve kidney function as measured by eGFR.
KEY WORDS
pentoxifylline renoprotection, pentoxifylline CKD , pentoxifylline nephropathy.This article is open to POST-PUBLICATION REVIEW. Registered readers (see "For Readers") may comment by clicking on ABSTRACT on the issue's contents page.
Topics: Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Animals; Diabetes Mellitus, Type 2; Glomerular Filtration Rate; Humans; Kidney Failure, Chronic; Kidney Function Tests; Pentoxifylline; Proteinuria
PubMed: 27096690
DOI: 10.18433/J3K020 -
The Journal of International Medical... Oct 2018Objective This study was performed to determine the healing effects of pentoxifylline on molecular responses and protection against severe ischemic damage in the small...
Objective This study was performed to determine the healing effects of pentoxifylline on molecular responses and protection against severe ischemic damage in the small intestine. Methods Thirty-six Wistar albino rats were divided into six groups. The superior mesenteric artery was clamped for 120 minutes, and reperfusion was performed for 60 minutes. Saline (0.4 mL), pentoxifylline (1 mg/kg), and pentoxifylline (10 mg/kg) were intraperitoneally administered to the rats in the C, P, and P groups, respectively, 60 minutes before ischemia and to the rats in the C, P, and P groups, respectively, during reperfusion onset. Malondialdehyde, myeloperoxidase, tumor necrosis factor alpha, interleukin-1 beta, and interleukin-6 in serum and tissue were measured by enzyme-linked immunosorbent assay. Intestinal ischemic injury was histopathologically evaluated by the Chiu score and immunohistochemical staining. Results All serum and tissue molecular responses were significantly blunted in the pentoxifylline-treated groups compared with the controls. Significant improvement in ischemic damage was demonstrated in the pentoxifylline-treated groups by histological grading and immunohistochemical scoring. Conclusions The protective effects of pentoxifylline were confirmed by molecular responses and histopathological examination.
Topics: Animals; Cardiovascular Agents; Disease Models, Animal; Hematologic Agents; Infusions, Parenteral; Intestine, Small; Ischemia; Male; Pentoxifylline; Protective Agents; Rats; Rats, Wistar; Reperfusion Injury; Wound Healing
PubMed: 30027781
DOI: 10.1177/0300060518786904 -
Cells Apr 2023Angiogenesis is the physiological process of developing new blood vessels to facilitate the delivery of oxygen and nutrients to meet the functional demands of growing... (Review)
Review
Angiogenesis is the physiological process of developing new blood vessels to facilitate the delivery of oxygen and nutrients to meet the functional demands of growing tissues. It also plays a vital role in the development of neoplastic disorders. Pentoxifylline (PTX) is a vasoactive synthetic methyl xanthine derivative used for decades to manage chronic occlusive vascular disorders. Recently, it has been proposed that PTX might have an inhibitory effect on the angiogenesis process. Here, we reviewed the modulatory effects of PTX on angiogenesis and its potential benefits in the clinical setting. Twenty-two studies met the inclusion and exclusion criteria. While sixteen studies demonstrated that pentoxifylline had an antiangiogenic effect, four suggested it had a proangiogenic effect, and two other studies showed it did not affect angiogenesis. All studies were either in vivo animal studies or in vitro animal and human cell models. Our findings suggest that pentoxifylline may affect the angiogenic process in experimental models. However, there is insufficient evidence to establish its role as an anti-angiogenesis agent in the clinical setting. These gaps in our knowledge regarding how pentoxifylline is implicated in host-biased metabolically taxing angiogenic switch may be via its adenosine A2BAR G protein-coupled receptor (GPCR) mechanism. GPCR receptors reinforce the importance of research to understand the mechanistic action of these drugs on the body as promising metabolic candidates. The specific mechanisms and details of the effects of pentoxifylline on host metabolism and energy homeostasis remain to be elucidated.
Topics: Animals; Humans; Pentoxifylline; Adenosine; Neoplasms
PubMed: 37190108
DOI: 10.3390/cells12081199 -
Digestive Diseases and Sciences May 2016Nonalcoholic fatty liver disease (NAFLD) is the most common cause of liver disease in the USA with a growing prevalence worldwide. Nonalcoholic steatohepatitis (NASH),... (Review)
Review
Nonalcoholic fatty liver disease (NAFLD) is the most common cause of liver disease in the USA with a growing prevalence worldwide. Nonalcoholic steatohepatitis (NASH), progressive form of NAFLD, can lead to the development of cirrhosis, hepatocellular carcinoma, and the need for liver transplantation. Treatment of NASH may decrease the risk of progressive disease. Treatment for NAFLD should center around weight loss and exercise. Pharmacotherapy with vitamin E and pioglitazone should be considered for those with NASH, especially those with fibrosis. Weight loss surgery is also an effective treatment for NASH in individuals with other indications for surgery. In this review, we will discuss the currently available therapies for NASH including lifestyle, pharmacologic, and surgical options.
Topics: Antioxidants; Bariatric Surgery; Exercise; Fatty Acids, Omega-6; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypoglycemic Agents; Non-alcoholic Fatty Liver Disease; Pentoxifylline; Pioglitazone; Thiazolidinediones; Vitamin E
PubMed: 26942734
DOI: 10.1007/s10620-016-4083-8 -
International Journal of Molecular... Jan 2018Renal ischemia-reperfusion injury (IRI) induces local inflammation leading to kidney damage. Since pentoxifylline (PTX) and steroids have distinct immunomodulatory...
Renal ischemia-reperfusion injury (IRI) induces local inflammation leading to kidney damage. Since pentoxifylline (PTX) and steroids have distinct immunomodulatory properties, we aimed to evaluate for the first time their combined use in IRI-induced acute kidney injury (AKI) and chronic kidney disease (CKD) in rats. In two experiments, PTX (100 mg/kg body weight subcutaneously) was administered 90 min prior to renal IRI or/and methylprednisolone (MP; 100 mg/kg body weight intramuscularly) was infused 60 min after reperfusion of a solitary kidney (AKI model: 45 min ischemia, 48 male Sprague-Dawley rats) or one kidney with excision of contralateral kidney 2 weeks later (CKD model: 90 min ischemia, 38 rats). Saline was infused in place of PTX or/and MP depending on the group. Renal function (diuresis, serum creatinine, creatinine clearance, sodium and potassium excretion, and urine protein/creatinine) was assessed at 48 h and 120 h post-IRI (AKI model) or 4, 16 and 24 weeks after IRI, along with survival analysis (CKD model). More evidently at early stages of AKI or CKD, treated animals showed higher glomerular filtration and diminished tubular loss of electrolytes, more so with PTX + MP than PTX or MP (serum creatinine (μmol/L) at 48 h of AKI: 60.9 ± 19.1 vs. 131.1 ± 94.4 vs. 233.4 ± 137.0, respectively, vs. 451.5 ± 114.4 in controls, all < 0.05; and at 4 weeks of CKD: 89.0 ± 31.9 vs. 118.1 ± 64.5 vs. 156.9 ± 72.6, respectively, vs. 222.9 ± 91.4 in controls, < 0.05 for PTX or PTX + MP vs. controls and PTX + MP vs. MP). Survival was better by >2-fold with PTX + MP (89%) vs. controls (40%; < 0.05). PTX + MP largely protect from IRI-induced AKI and CKD and subsequent mortality in rats. This calls for clinical investigations, especially in kidney transplantation.
Topics: Acute Kidney Injury; Animals; Glucocorticoids; Kidney; Male; Methylprednisolone; Pentoxifylline; Rats; Rats, Sprague-Dawley; Reperfusion Injury; Vasodilator Agents
PubMed: 29324683
DOI: 10.3390/ijms19010221 -
The Cochrane Database of Systematic... Apr 2008There is increasing evidence that capillary occlusion plays an important part in the development of diabetic retinopathy. Disaggregants, such as pentoxyfilline may... (Review)
Review
BACKGROUND
There is increasing evidence that capillary occlusion plays an important part in the development of diabetic retinopathy. Disaggregants, such as pentoxyfilline may influence the outcome and progression of diabetic retinopathy, but no systematic review of the literature on its efficacy and safety has been published to examine this hypothesis.
OBJECTIVES
The aim of the current research was to review the literature in a systematic way in order to assess the effects of pentoxyfilline for diabetic retinopathy in methodologically robust trials. The null hypothesis was that pentoxyfilline has no influence on the progression of diabetic retinopathy or blindness.
SEARCH STRATEGY
A systematic search of electronic databases was carried out to identify publications. Relevant papers, written in any language, were accessed and assessed for data.
SELECTION CRITERIA
Only randomized controlled clinical trials (RCTs) evaluating the effects of pentoxyfilline in the treatment of diabetic retinopathy were to be included.
DATA COLLECTION AND ANALYSIS
Two authors independently assessed studies for inclusion criteria and for risk of bias.
MAIN RESULTS
A total of 97 publications were identified by the electronic search and two authors checked the abstracts. Of these, 17 were identified as potentially relevant trials providing information about treatment of patients with diabetic retinopathy using pentoxyfilline and were read in full. Unfortunately, no publication fulfilled our inclusion criteria.
AUTHORS' CONCLUSIONS
No sound research to date has examined the treatment of diabetic retinopathy with pentoxyfilline in such a way as to indicate whether this form of intervention has a significant impact on the natural history of this clinical condition. The potential role of this substance in the treatment of diabetic retinopathy remains open to debate, and it is suggested that future research focusing on patient-relevant outcomes takes the opportunity of addressing this important issue directly.
Topics: Diabetic Retinopathy; Humans; Pentoxifylline; Vasodilator Agents
PubMed: 18425965
DOI: 10.1002/14651858.CD006693.pub2 -
World Journal of Gastroenterology Oct 2012Alcohol related costs to health and society are high. One of the most serious complications of alcohol misuse to the individual is the development of alcoholic hepatitis... (Review)
Review
Alcohol related costs to health and society are high. One of the most serious complications of alcohol misuse to the individual is the development of alcoholic hepatitis (AH), a clinical syndrome of jaundice and progressive inflammatory liver injury in patients with a history of recent heavy alcohol use. It has a poor outcome and few existing successful therapies. The use of glucocorticoids in patients with severe AH is still controversial and there remains a group of patients with glucocorticoid-resistant disease. However, as our understanding of the pathogenesis of the condition improves there are opportunities to develop new targeted therapies with specific actions to control liver inflammation without having a detrimental effect on the immune system as a whole. In this article we review the molecular mechanisms of AH concentrating on the activation of the innate and adaptive immune response. We consider existing treatments including glucocorticoids, anti-tumor necrosis factor therapy and pentoxifylline and their limitations. Using our knowledge of the disease pathogenesis we discuss possible novel therapeutic approaches. New targets include pro-inflammatory cytokines such as interleukin (IL)-17, chemokines and their receptors (for example IL-8, CXCL9 and CXCR3) and augmentation of anti-inflammatory molecules such as IL-10 and IL-22. And there is also future potential to consider combination therapy to selectively modulate the immune response and gain control of disease.
Topics: Animals; Hepatitis, Alcoholic; Humans; Molecular Targeted Therapy; Pentoxifylline; Phosphodiesterase Inhibitors; Tumor Necrosis Factor-alpha
PubMed: 23112542
DOI: 10.3748/wjg.v18.i39.5504 -
Journal of Pharmacy & Pharmaceutical... 2011Chronic kidney disease (CKD) as a considerable health problem may have proteinuria as the main complication and strong risk factor to reach end-stage renal disease... (Review)
Review
Chronic kidney disease (CKD) as a considerable health problem may have proteinuria as the main complication and strong risk factor to reach end-stage renal disease (ESRD). Decreasing proteinuria is the mainstay of therapy in order to delay the progression of CKD. Current therapeutic regimens provide only partial renoprotection, and a substantial number of patients who have proteinuria progress to ESRD. Pentoxifylline (PTF) is known for its potent inhibitory effects against cell proliferation and inflammation which play important roles in CKD progression. Data derived from both human studies and animal models demonstrated that PTF has broad-spectrum renoprotective effects and therefore, provide a scientific basis for the use of PTF as an anti-proteinuric agent. Conclusion of this review is that short-term use of PTF may produce a significant reduction of proteinuria in subjects with diabetic and also non-diabetic kidney diseases but the reports of long-term use of PTF also show that urinary protein excretion exhibits a progressive and sustained reduction in patients treated with PTF. Whether the long-term use of PTF could be a pharmacological alternative for delaying or preventing the development of end stage renal disease, is among the questions that remained to be appropriately answered in large-scale clinical trials.
Topics: Animals; Chronic Disease; Diabetic Nephropathies; Disease Progression; Humans; Kidney Diseases; Kidney Failure, Chronic; Pentoxifylline; Phosphodiesterase Inhibitors; Proteinuria; Risk Factors; Time Factors
PubMed: 21501559
DOI: 10.18433/j3bp4g -
Antimicrobial Agents and Chemotherapy Sep 1998Pentoxifylline has immunomodulatory properties and has been shown to decrease organ damage and improve survival in animals with gram-negative sepsis or endotoxemia. This...
Pentoxifylline has immunomodulatory properties and has been shown to decrease organ damage and improve survival in animals with gram-negative sepsis or endotoxemia. This effect is mediated by a reduction in endotoxin-induced production of tumor necrosis factor alpha (TNF-alpha) by the host. In earlier studies, we observed an unexpected increase in mortality in mice infected with Candida albicans that were given pentoxifylline even though concentrations of TNF-alpha in serum were not affected. The current study was designed to determine whether the pharmacokinetics of pentoxifylline and its metabolites were altered in C. albicans-infected mice and, if so, whether these changes could have contributed to the increased mortality. Noninfected mice and mice infected with C. albicans were treated with pentoxifylline (60 mg/kg of body weight) intraperitoneally every 8 h. Serum was collected from animals after one (day 0), four (day 1), or seven (day 2) injections of pentoxifylline or saline (controls). The first dose was administered 6 h after C. albicans infection. Serum was pooled. Concentrations of pentoxifylline and metabolites I, IV, and V were determined by capillary gas chromatography. Renal function and hepatic profiles were assessed. Pharmacokinetic parameters (maximum concentration of pentoxifylline in serum, half-life, and area under the concentration-time curve from 0 h to infinity [AUC(0)-infinity]) for all noninfected mice were similar and did not differ from those for day 0-infected mice. For day 1-infected mice, values of these three pharmacokinetic parameters for pentoxifylline and metabolite I were increased two- to fourfold over values for noninfected and day 0-infected mice. For metabolites IV and V, the AUC(0)-infinity was increased approximately eightfold over control values. In addition, day 1-infected mice demonstrated evidence of renal and hepatic dysfunction. In summary, C. albicans infection produced marked changes in the pharmacokinetics of pentoxifylline and its metabolites in the mice. The high concentrations of pentoxifylline and its metabolites in serum attained in infected mice may have contributed to the increased mortality of mice with systemic candidiasis.
Topics: Adjuvants, Immunologic; Animals; Candidiasis; Female; Mice; Pentoxifylline
PubMed: 9736571
DOI: 10.1128/AAC.42.9.2405 -
Canadian Family Physician Medecin de... Mar 2008
Topics: Adult; Anti-Inflammatory Agents, Non-Steroidal; Antibiotic Prophylaxis; Anticoagulants; Aspirin; Bencyclane; Clinical Protocols; Dextrans; Frostbite; Humans; Ibuprofen; Male; Military Personnel; Pentoxifylline; Platelet Aggregation Inhibitors; Rewarming; Vasodilator Agents
PubMed: 18337529
DOI: No ID Found