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Radiation treatment plays a mainstream role in the management of head and necksquamous cell carcinomas (HNSCCs). Adverse effects from radiation therapy include osteoradionecrosis of the jaw, and rarely, pathologic fracture. Immune checkpoint inhibitors (ICI) such as pembrolizumab are of growing relevance to the management of metastatic and recurrent HNSCCs. Adverse impacts on bone secondary to medications such as pembrolizumab and nivolumab have been sporadically documented in the literature. The objective of this manuscript is to raise awareness of possible increase in risk for adverse jaw outcomes in patients with HNSCCs exposed to both radiation treatment to the jaws and ICI therapy. This manuscript documents adverse jaw outcomes including osteonecrosis and pathologic fracture of the mandible in two patients receiving pembrolizumab for management of HNSCC who had received prior radiation treatment. A potential link between immunotherapy and adverse jaw outcomes is consistent with the growing understanding of osteoimmunology, investigating the closely interrelated processes in bone remodeling and immune system function, in health and disease. It is important to ascertain if pembrolizumab poses an incremental risk for such outcomes, beyond the risk from prior radiation, for patients managed with radiation treatment and ICI therapy for HNSCC. The general dental practitioner may encoun-tersuch patients either in the context of facilitating dental clearance prior to initiation of chemotherapy, or rarely, with poorly explained jaw symptoms and must be alert to the possibility of occurrence of such adverse jaw events to facilitate timely diagnosis and optimal patient management. [ABSTRACT FROM AUTHOR]

This study evaluated the effects of oral pentoxifylline on testicular biometry, histology, and gene expression in stallions subjected to scrotal heat stress. Fourteen stallions were divided into three groups: Control (CRL, n = 4), Testicular Degeneration (DEG, n = 5), and Testicular Degeneration Treated with Pentoxifylline (DEG + PTX, n = 5). Testicular degeneration was induced by scrotal insulation, twice daily, over two consecutive days (D-1 and D0). Starting the next day (D1), oral pentoxifylline (17 mg/kg) was administered every 12 h for 30 days. Testicular biometry was measured using a caliper from D-5 to D60. On days 30 and 60, testicular biopsies were collected for histopathology and gene expression analysis of BAX , CASP8 , CASP9 , FAS , HSF1 , and PTGS2 using RT-qPCR. Pentoxifylline reduced histological damage, with the DEG + PTX group showing less pronounced basal lamina undulation and seminiferous tubule atrophy compared to the DEG group. However, it did not fully prevent lesions like germ cell vacuolization, which was reflected macroscopically by a reduction in testicular volume in both degenerated groups. The protective effects of pentoxifylline on testicular tissue can be attributed to its ability to reduce BAX expression, prevent CASP8 and CASP9 activation, and promote cellular protective mechanisms through HSF1 activation at D30. These results highlight pentoxifylline's potential as a therapeutic agent for equine testicular damage due to scrotal heat stress, suggesting the need for further research on optimal dosage and treatment duration. • Scrotal insulation using a forced hot air system at 45 °C effectively induces testicular degeneration. • Scrotal heat stress activates germ cell apoptosis and leads to severe testicular degeneration. • Oral treatment with pentoxifylline reduces parenchymal damage, including mitigating seminiferous tubule atrophy. • Pentoxifylline decreases germ cell apoptosis by downregulating BAX and preventing the activation of CASP8 and CASP9. [ABSTRACT FROM AUTHOR]

Several treatment modalities have been used for the treatment of keloid scarring but the optimal treatment has not yet been identified. Corticosteroids reduce excessive scarring by reducing collagen synthesis. Vitamin D can curb inflammation by inhibiting the activation and migration of leukocytes. Pentoxifylline is a methyl xanthine derivative initially developed for its vasodilatory properties. Evaluation and comparison between three modalities of treatment for keloid; intralesional vitamin D, pentoxifylline, and steroid. Forty-five patients with keloid lesions were divided into 3 groups; The first group: 15 patients were treated with intralesional triamcinolone acetonide. The second group: 15 patients treated with intralesional pentoxifylline. The third group: 15 patients treated with intralesional vitamin D. The response was evaluated clinically, Vancouver scar scale and patient satisfaction scale. At the end of the study, all groups showed highly statistically significant improvement compared to the baseline. The first group which was treated with triamcinolone acetonide showed excellent and good improvement 53% and 47% respectively. The second group which was treated with pentoxifylline showed excellent and good improvement 6.7% and 73.3% respectively. The third group which was treated with vitamin D showed excellent and good 6.7% and 86.7% respectively. Intralesional vitamin D and pentoxifylline are safe and effective therapeutic options for keloid lesions. [ABSTRACT FROM AUTHOR]

Background: Alveolar osteitis is a type of small-scale osteomyelitis of the alveolar bone that occurs after tooth extraction, the etiology of which remains unknown, and alternative methods are being investigated for its treatment. The aim of this study was to compare the effectiveness of advanced platelet-rich fibrin (A-PRF), photobiomodulation (PBM), and Alveogyl (butamben, idoform, eugenol), which have shown success in the treatment of alveolar osteitis, with that of pentoxifylline (PTX) to determine whether PTX could be an alternative treatment for alveolar osteitis. Methods: This study included 80 healthy volunteers diagnosed with alveolar osteitis in the extraction sockets of their mandibular first, second, and third molars. The patients were divided into four groups, with 20 patients in each group: A-PRF, PBM, PTX, and Alveogyl. After physiological saline irrigation, the patients were treated according to their respective group. The patients were followed up on the 2nd, 4th, 7th, and 14th days. Primary outcomes included pain assessment and the evaluation of soft tissue healing. Pain was assessed via the visual analog scale (VAS), soft tissue healing was evaluated via the Landry Healing Index (LHI), and granulation tissue was measured. Age and sex were used as study variables. The data were analyzed via ANOVA and post hoc tests to compare the treatment groups. Results: There was no statistically significant difference in the mean VAS score between the groups (p > 0.05). However, the degree of reduction in the VAS score increased in the following order: A-PRF, PBM, PTX, and Alveogyl. In the LHI data, there was a statistically significant difference in the mean scores between the groups, with Alveogyl being favored preoperatively and PBM being favored at the 2nd week (p < 0.05). Statistically significant differences were observed in granulation tissue measurements on the preoperative day, as well as on Days 4 and 7, in favor of Alveogyl on Day 4 and PBM on Day 7 (p < 0.05). The greatest increase in granulation tissue scores was observed in the A-PRF group, whereas the greatest change in LHI scores was observed in the PBM group. PTX did not produce a statistically significant difference in soft tissue healing, although there were periods when it showed results similar to those of Alveogyl and PBM. There were significant differences between the VAS score, granulation tissue score and LHI score in terms of age and sex within the time periods followed. Conclusion: The findings of this study indicate that although PTX has similar efficacy in terms of wound healing and analgesic properties to the methods used, it does not offer significant advantages. Compared with other methods, A-PRF and PBM have provided better results in the treatment of alveolar osteitis, particularly regarding pain and soft tissue healing. Trial registration: The study was retrospectively registered in the clinical trial registry with the number TCTR20231014003 on 14.10.2023. [ABSTRACT FROM AUTHOR]

An efficient, facile, and one‐pot route has been utilized for the synthesis of a new series of 3,7‐dimethyl‐1‐(5‐(2‐(4‐substitutedphenylthiazol‐2‐yl)hydrazono)hexyl)‐1H‐purine‐2,6(3H,7H)‐dione (4a–4j). The pentoxifylline (1) as a novel precursor, thiosemicarbazide, and a variety of phenacyl bromides have been employed to generate a newer pentoxifylline‐thiazole adduct using PPA as the green catalyst at reflux conditions to afford a high yield and pure product. All the synthesized compounds were purified using chromatographic methods and characterized by spectroscopic techniques (1H and 13C NMR, MS, and IR). Antioxidant activity was assessed using a DPPH free radical scavenging assay, and it was observed that compounds with cyano functional groups and electron‐donating groups showed notably higher potency, with IC50 values around 400 µM, while those with halogens and nitro functional groups displayed moderate efficacy (IC50 ≈600 µM). These results were compared to the standard ascorbic acid, which had an IC50 of 382.54 ± 5.09 µM. Molecular docking was performed on the myeloperoxidase (MPO) enzyme to explore the mechanistic basis of antioxidant activity, providing valuable insights into the thermodynamic interactions that contribute to binding affinity. [ABSTRACT FROM AUTHOR]

A single-oral-dose, two-period cross-over study with a 5-day washout period under fed condition was conducted in six beagle dogs to explore the pharmacokinetic characteristics and relative bioavailability between sustained-release (SR) tablets and enteric-coated (EC) tablets of pentoxifylline (PTX) and its metabolite. The results showed that M5 exhibited the highest exposure level, while M1 demonstrated the lowest in both the SR and EC tablet groups. For PTX and M1, T1/2 were 0.42 and 0.55 h, with tmax of 1.83 and 1.83 h, respectively, in the SR tablet group; in the EC tablet group, T1/2 were 0.38 and 0.47 h, respectively. However, a significantly prolonged absorption process was noted, with tmax values of 5.06 and 5.78 h. In contrast, M5 exhibited distinct pharmacokinetic differences compared to PTX and M1. For the SR tablet group, T1/2 and tmax were recorded at 2.03 and 3.08 h, respectively. In the EC tablet group, T1/2 and tmax were 1.67 and 5.78 h, respectively. With regard to the geometric least squares mean (LSM) of AUC and Cmax for SR tablets and EC tablets, the ratios of SR/EC of PTX, M1 and M5 were 67.62% (90% CI, 50.49%–90.55%), 78.18% (90% CI, 54.15%–112.88%), and 119.11% (90% CI, 99.62%–142.41%), respectively, for AUC(0-t). The ratios were 67.62% (90% CI, 50.50%–90.55%), 78.36% (90% CI, 54.48%–112.72%), and 119.39% (90% CI, 100.03%–142.50%) for AUC(0−∞) and 54.36% (90% CI, 36.63%–80.67%), 58.80% (90% CI, 40.84%–84.66%), and 100.51% (90% CI, 89.50%–112.88%) for Cmax, respectively. The AUC ratio predictions of bioconversion results indicated that there was no significant difference in the bioconversion of M1 between the SR tablets and EC tablets, with conversion rates of 0.37 and 0.36, respectively. In contrast, the conversion rate of M5 demonstrated a significant difference (p < 0.05) between the SR tablets and EC tablets, with the ratio of 3.09 and 1.91, respectively. Furthermore, the EC tablet group demonstrated notable inter-individual differences and irregular drug absorption, following meals. Consequently, the SR tablets appeared to provide a more stable and controllable therapeutic effect in beagle dogs. [ABSTRACT FROM AUTHOR]

Introduction: Pentoxifylline (PTX) affects most blood components and the blood vessels, potentially modulating various conditions. Due to its impact on markers linked to COVID-19 severity, research has explored PTX for acute COVID-19. Following the widespread administration of COVID-19 vaccinations, there has been a notable and consistently growing increase in research focusing on long COVID. Consequently, our examination of relevant acute COVID-19 data shall additionally be contextualized into long COVID research. Methods: Various Databases were searched until July 2024 for all primary clinical studies on Pentoxifylline (PTX) in COVID-19. Results: Studies were on acute infection with SARS-CoV-2 where PTX was an adjuvant to standard therapy for ethical and practical reasons under the circumstance. PTX generally reduced hospitalization duration and improved some inflammatory markers, but its impact on mortality was inconsistent. Adverse events were minimal. Meta-analysis revealed a significant reduction in hospitalization duration. Conclusion: This systematic review and meta-analysis suggest that adding pentoxifylline (PTX) to standard COVID-19 therapy may significantly reduce hospitalization duration and improve some inflammatory markers. However, its impact on mortality rates is inconclusive. Adverse events are minimal. PTX can be favorable as an add-on in managing acute COVID-19 and could reduce the risk of long COVID, as well as assist in managing many of its most common symptoms. [ABSTRACT FROM AUTHOR]

Objective: The role of propionic acid (PPA) in eliciting behaviors analogous to autism in rat models is a documented phenomenon. This study examines the therapeutic implications of pentoxifylline—an agent traditionally used for peripheral vascular diseases—on these autism‐like behaviors by modulating brain proteins and reducing pro‐inflammatory cytokines like tumor necrosis factor‐α (TNF‐α) in a rat model. Methods: This research involved 30 male Wistar albino rats, which were divided into three distinct groups: a baseline control set, a PPA‐treated cluster receiving a 250 mg/kg/day dose of PPA via intraperitoneal injection for a span of five days followed by saline orally, and a PPA group administered an oral dose of pentoxifylline at 300 mg/kg/day over 15 days. Subsequent to the treatment phase, euthanasia was carried out for the extraction of brain and blood samples, which were then analyzed for histopathological and biochemical markers. Results: The pentoxifylline‐treated subjects demonstrated a significant mitigation in the manifestation of autistic‐like behaviors, as assessed through a triad of social interaction tests. A noteworthy decline in TNF‐α levels was observed, alongside a significant rise in the concentration of adenosine triphosphate and nerve growth factor in brain tissue (p < 0.05). Histopathological analysis underscored a reduction in oxidative stress and a significant preservation of neuronal cell types, specifically pyramidal neurons in the hippocampal CA1 and CA3 regions and Purkinje cells in the cerebellum (p < 0.001). Conclusion: Pentoxifylline treatment has been found to effectively reduce the behavioral symptoms associated with autism, as well as biochemical and histopathological disruptions induced by PPA in rat models, highlighting its potential as a neurotherapeutic agent. [ABSTRACT FROM AUTHOR]

This study presents an analysis of In Vitro-In Vivo Correlation (IVIVC) for pentoxifylline modified-release tablets, with a focus on deriving robust predictive models. In vitro dissolution tests were conducted in three pH media (1.2, 4.5, and 6.8) to simulate various gastrointestinal conditions. Data was collected under fed conditions from a bioequivalence (BE) study. The modeling and calculations were performed using Phoenix WinNonlin® version 8.4 software, enabling estimation of drug absorption kinetics. A Level A IVIVC model was employed for each in vivo data to establish a direct and reliable correlation between the in vitro dissolution profiles and the in vivo pharmacokinetic data. The determination coefficient (R²) exceeded 0.97, demonstrating a high degree of predictability and robustness in the established IVIVC. [ABSTRACT FROM AUTHOR]

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The article outlines evidence-based guidelines for preventing and managing osteoradionecrosis in patients with head and neck cancer undergoing radiation therapy. Topics include radiation treatment planning to minimize osteoradionecrosis risk, the timing and frequency of dental evaluations for at-risk patients, and the use of systemic therapies or hyperbaric oxygen to reduce osteoradionecrosis incidence in high-risk individuals.

Alterations in the gastric mucosal barrier, one of whose fundamental components is phosphatidylcholine (PC), may play an important role in the pathophysiology of erosive gastritis secondary to sepsis. Pentoxifylline (PTX) has been shown to reduce tissue damage in various experimental models of sepsis. The aim of this study was to investigate the effect of PTX on gastric mucosa PC synthesis, leukocyte infiltration, arachidonic acid-related metabolites, inflammation, oxidative stress, NO, CO, and somatostatin in a rat model of LPS-induced sepsis. Rats were administered LPS (10 mg/kg b.w.) intraperitoneally. After 30 min (early treatment group) or 120 min (late treatment group) of LPS administration, they were randomly divided into two groups that were intraperitoneally administered saline (5 mL/kg; LPS + Saline group) or PTX (45 mg/kg; 5 mL/kg; LPS + PTX group). Control rats received only saline instead of LPS and/or PTX. Two hours after saline or PTX administration (total of 150 or 240 min of procedure), animals were anesthetized, and then gastric lavage, gastric mucosa and plasma samples were obtained and kept frozen until determination. LPS-induced sepsis changed the gastric mucosal barrier by reducing its phospholipid content, PGI2, and somatostatin levels, as well as increasing MPO, TXB2, LTB4, PLA2, and MDA. Alterations may be mediated, at least in part, by modifications in the production of NO, CO, and cGMP content. PTX had a beneficial effect on gastric lesions secondary to sepsis by restoring PC production. [ABSTRACT FROM AUTHOR]

There is limited understanding of the optimal duration and dosage of pentoxifylline (PTX) therapy required to achieve significant reductions in atherosclerotic cardiovascular disease (ASCVD) risk, particularly in patients with diabetic kidney disease (DKD). This study aimed to evaluate the impact of long-term PTX therapy on the risk of ASCVD in patients with DKD who do not have pre-existing cardiovascular disease, while also exploring potential vascular protective mechanisms. This retrospective cohort study included data from Taiwan's Ministry of Health and Welfare's Health and Welfare Data Science Center. In 2008–2019, we identified and analyzed a specific sample of 129,764 patients with DKD without established cardiovascular disease. Participants were categorized according to their PTX treatment regimen. Short-term PTX users (<763 days) had a greater risk of developing ASCVD than non-PTX users. However, those who used PTX for >763 days (long-term PTX treatment) had a significantly lower risk of ASCVD, with a 47% lower cumulative incidence. A dose-dependent reduction in apoptosis was observed via Klotho treatment in cultured human aortic endothelial cells following PTX treatment. Long-term PTX treatment (24 h) caused a higher reduction in H2O2-induced reactive oxygen species production and cell apoptosis than short-term PTX treatment (2 h). In the DKD mice model experiments, PTX reduced the ASCVD risk by increasing the Klotho levels to inhibit endothelial cell damage. These findings suggest that the cardiovascular and renoprotective benefits of PTX may be extended to primary prevention strategies for people with DKD. [ABSTRACT FROM AUTHOR]

Abstract Background Alveolar osteitis is a type of small-scale osteomyelitis of the alveolar bone that occurs after tooth extraction, the etiology of which remains unknown, and alternative methods are being investigated for its treatment. The aim of this study was to compare the effectiveness of advanced platelet-rich fibrin (A-PRF), photobiomodulation (PBM), and Alveogyl (butamben, idoform, eugenol), which have shown success in the treatment of alveolar osteitis, with that of pentoxifylline (PTX) to determine whether PTX could be an alternative treatment for alveolar osteitis. Methods This study included 80 healthy volunteers diagnosed with alveolar osteitis in the extraction sockets of their mandibular first, second, and third molars. The patients were divided into four groups, with 20 patients in each group: A-PRF, PBM, PTX, and Alveogyl. After physiological saline irrigation, the patients were treated according to their respective group. The patients were followed up on the 2nd, 4th, 7th, and 14th days. Primary outcomes included pain assessment and the evaluation of soft tissue healing. Pain was assessed via the visual analog scale (VAS), soft tissue healing was evaluated via the Landry Healing Index (LHI), and granulation tissue was measured. Age and sex were used as study variables. The data were analyzed via ANOVA and post hoc tests to compare the treatment groups. Results There was no statistically significant difference in the mean VAS score between the groups (p > 0.05). However, the degree of reduction in the VAS score increased in the following order: A-PRF, PBM, PTX, and Alveogyl. In the LHI data, there was a statistically significant difference in the mean scores between the groups, with Alveogyl being favored preoperatively and PBM being favored at the 2nd week (p

Cognitive impairment is one of the key manifestations of chronic cerebrovascular diseases. Among the factors contributing to their development are microcirculatory disturbances, changes in blood rheological properties, endothelial dysfunction and oxidative stress. This review is devoted to the analysis of the clinical application potential of the nonspecific phosphodiesterase inhibitor pentoxifylline (Vasonit®) in the therapy of patients with chronic cerebral ischaemia in order to correct haemorheological and haemodynamic factors. Data from experimental and clinical studies indicating the possibility and pathogenetic validity of the use of pentoxifylline (Vasonit®) in the complex therapy of cognitive disorders associated with chronic cerebrovascular diseases are considered. The authors describe their own experience of using Vasonit® in a patient with vascular cognitive impairment.

Oral submucous fibrosis (OSF) is an oral potentially malignant disorader that may be closely related to betel chewing and other factors. The pathogenic mechanism of OSF is still unclear, and there is no cure for OSF. Currently, there are many clinical treatments for OSF, such as medications, including steroids, pentoxifylline, lycopene, turmeric, salvia miltiorrhiza, and aloe vera, lasers, and surgery. In order to evaluate the safety and efficacy of these methods to improve the maximum mouth opening, alleviate the burning sensation, increase tongue flexibility, and other symptoms that accompany OSF, researchers have completed some evidence-based studies in recent years. We searched PubMed, Embase, Web of Science, The Cochrane Library, CNKI, Wanfang, and VIP databases for systematic reviews or meta-analyses of OSF research and treatment published over the last 10 years (July 2014-July 2024). Current evidence-based studies have shown that pentoxifylline, hyaluronidase combined with steroids, lycopene, curcumin, salvia miltiorrhiza combined with steroids, and aloe vera are effective in improving maximum mouth opening and alleviating the burning sensation in patients with OSF. The evidence levels of hyaluronidase combined with steroids, lycopene, curcumin, salvia miltiorrhiza combined with steroids, and aloe vera were all A, and pentoxifylline was B. Lycopene was more effective than other positive drugs in improving maximum mouth opening in patients, and aloe vera was more effective than positive drugs in improving the burning sensation in the early stage of treatment. In addition, antioxidants are good for improving OSF symptoms and have promising application. Lasers can improve maximum mouth opening and alleviate pain and other OSF symptoms, but laser treatment is costly and the level of evidence is C. Surgery is effective in improving maximum mouth opening, but it is traumatic and the level of evidence is C. However, the current evidence-based data are not of high quality, and additional well-designed multi-center, large-sample, randomized controlled clinical trials with long follow-up periods and standardized outcome indicators are needed in the future.

Introduction: Epilepsy remains a challenge, with one-third of patients experiencing refractory seizures despite current anti-seizure medications. The nitrergic system, which involves nitric oxide (NO) and NO synthase (NOS) enzymes, plays a complex role in seizure pathophysiology. Pentoxifylline (PTPh), an FDA-approved phosphodiesterase inhibitor, has anticonvulsant effects; however, its relationship with the pathway is unclear. This study focused at how the nitrergic system could be involved in PTPh’s anticonvulsant effects. Methods: Seizures were induced in male mice by intravenous pentylenetetrazole (PTZ) infusion (absence-like seizures), intraperitoneal PTZ injection, and maximal electroshock (generalized tonic-clonic seizures). PTPh was administered at various doses, alone or in combination with the NO precursor L-arginine, as well as non-selective (L-NAME) and selective NOS inhibitors (nNOS inhibitor 7-NI and iNOS inhibitor aminoguanidine). Seizure thresholds, latencies, incidence, and mortality were assessed. Moreover, in the next paradigm, using maximal electroshock model, we evaluate possible protective effects of PTPh against generalized tonic-clonic seizures and subsequent mortality. Results: In the intravenous PTZ model, PTPh (≥150 mg/kg) increased the seizure threshold, potentiated by L-arginine but reduced by L-NAME and 7-nitroindazole. In the intraperitoneal PTZ model, 150 mg/kg PTPh decreased tonic seizure frequency, which was mitigated by aminoguanidine. However, PTPh failed to prolong clonic seizure latency. In the maximal electroshock test, 100 mg/kg PTPh protected against tonic seizure incidence (reduced by aminoguanidine). Although PTPh could not reduce mortality, its combination with L-NAME or 7-nitroindazole increased mortality compared with the vehicle-treated group. Conclusion: PTPh exerted anticonvulsant effects against absence-like and generalized tonic-clonic seizures, likely through modulation of the nitrergic system involving neuronal, endothelial, and inducible NOS isoform. These findings provide novel insights into the complex interplay between NO signaling and the anticonvulsant actions of PTPh, highlighting the potential therapeutic implications of targeting the NO pathway in epilepsy management.

Objective(s): To investigate the impact of Pentoxifylline (PTX) on the in vitro maturation (IVM) of mouse oocytes and its effect on oocyte quality. Materials and Methods: This experimental study involved culturing mouse oocytes in an IVM medium with varying PTX concentrations (0-100 µM). Post-culture, oocytes were assessed for nuclear and cytoplasmic maturation and quality indicators, including germinal vesicle breakdown (GVBD), first polar body extrusion (PB1E), cortical granules (CGs) distribution, spindle structure, chromosome alignment, and intracellular reactive oxygen species (ROS) levels. Results: Treatment with PTX at 10, 25, and 50 µM concentrations significantly enhanced the nuclear maturation rates of oocytes. The optimal concentration was found to be 10 µM, as it resulted in the most favorable cytoplasmic maturation, characterized by improved distribution of CGs, spindle structure, and chromosome alignment. Additionally, treatment with 10 µM PTX effectively reduced reactive oxygen species (ROS) levels. Conclusion: PTX supplementation at specific concentrations enhances mouse oocyte maturation and quality, potentially by facilitating CG distribution, spindle integrity, and chromosome alignment and by reducing ROS production. [ABSTRACT FROM AUTHOR]

Abstract We systematically reviewed the evidence from animal studies assessing the effects of pentoxifylline on neonatal hypoxic-ischemic encephalopathy (HIE). The PubMed, EMBASE, EMCARE, MEDLINE, Cochrane Library, and Google Scholar databases were searched for randomized and quasi randomized controlled trials (RCTs) in December 2023 to determine the effects of pentoxifylline in animal models of HIE. The quality of the included studies was assessed via the SYRCLE risk of bias (ROB) tool. The certainty of evidence was assessed via the GRADE methodology. All seven included studies (n = 248) involved a rat HIE model in which pentoxifylline (25–150 mg/kg) was administered intraperitoneally. The majority had unclear ROB. All the studies reported a protective effect of pentoxifylline on HIE-induced organ injury. Mortality was comparable at pentoxifylline doses between 25 and 75 mg/kg but higher at 150 mg/kg than in the control group. Three studies reported macroscopic changes in HIE-affected organs. There was a significant reduction in cerebral infarction (40 and 75 mg/kg), hippocampal atrophy, and visible gut injury (60 mg/kg). A significantly lower number of Caspase 3 immunoreactive cells and necrotic cells were observed at the 60 mg/kg dose, whereas the 100 mg/kg dose had a deleterious effect. Three other studies reported significantly reduced levels of proinflammatory markers including IL-6 and TNF-alpha. Current evidence (with low uncertainty) from a rat model suggests that pentoxifylline has the potential to improve mortality and attenuate organ injury following HIE. Adequately powered, well-designed human RCTs are needed to confirm our findings.

Abstract Background Paclitaxel-induced peripheral neuropathy (PIPN) is one of the most common and debilitating toxicity. Up till now, no treatment or preventive medication is recommended by guidelines. Pentoxifylline has been found to prevent PIPN in animal models. This study aimed to evaluate the tolerability and efficacy of pentoxifylline in preventing PIPN. To our knowledge, this is the first clinical trial to evaluate the potential effect of pentoxifylline on the prevention of PIPN in breast cancer (BC) patients. Results A simple-randomized placebo-controlled study was conducted on 60 BC patients receiving weekly paclitaxel and either pentoxifylline 400 mg twice daily (n = 30) or placebo (n = 30) for 12 weeks. Only 55 patients completed the study. The main objective was the evaluation of the effect of pentoxifylline on the incidence of PIPN which revealed no significant difference between the pentoxifylline group (85%) and the placebo group (100%). Secondary objectives included time to develop grade 2 or 3 (TTG 2/3) PIPN, the patient’s quality of life (QOL), serum tumor necrosis factor-α (TNF-α) and malondialdehyde and the tolerability of pentoxifylline. The median TTG 2/3 PIPN was not reached in the pentoxifylline group compared to 77 days (95% confidence interval of 70.91 to 83.07) in the placebo group. However, the difference did not reach significance. The assessment of the impact of PIPN on QOL was performed at baseline and at weeks 4, 8 and 12 using Functional Assessment of Cancer Therapy/Gynecologic Oncology Group-Neurotoxicity (FACT/GOG-NTX) subscale. The magnitude of the worsening in the QOL was significantly lower in the pentoxifylline group than in the placebo group at weeks 4, 8, and 12 (p values = 0.028, 0.003, and 0.018, respectively). Analysis of the serum TNF-α and malondialdehyde revealed no significant differences between the groups. Pentoxifylline was safe, tolerable and did not affect paclitaxel toxicity. Conclusion Oral pentoxifylline (400 mg twice daily) did not decrease the incidence of PIPN. However, it improved patients’ QOL significantly. Trial registration Clinical Trials.gov, NCT05189535. Registered 4 October 2021, https://classic.clinicaltrials.gov/ct2/show/NCT05189535 .

Prostate cancer (PCa) is a common and deadly disease in men. It is often diagnosed at advanced stages, at which point patients are treated mainly with docetaxel (DTX), which is effective but limited by resistance and side effects. Overactivation of the transcription factors NF-κB and STAT-3 plays a critical role in the development, progression, and chemoresistance of PCa. In this regard, the blockade of NF-κB with pentoxifylline (PTX) or STAT-3 with Stattic (STT) is known to increase the sensitivity of tumor cells to chemotherapy in both in vitro and in vivo models. We investigated whether simultaneous blockade with PTX and STT increases the efficacy of the DTX treatment in inducing apoptosis in metastatic castration-resistant PCa DU-145 cells. Our results showed that the combination of PTX + STT led to higher levels of apoptosis, regardless of whether or not DTX was present in the treatment. Determining caspases and ΔΨm indicates that the intrinsic caspase pathway of apoptosis is principally favored. In addition, this combination inhibited proliferation and colony formation and arrested the cell cycle in the G1 phase. These results indicate that the combination of the PTX + STAT-3 inhibitor could potentiate DTX effectively, opening the possibility of effective treatments in PCa.

Background: The combination of oral pentoxifylline (Ptx) and vitamin E (VitE) has been used to treat radiation-induced fibrosis and soft tissue injury. Here, we review outcomes and perform a radiomic analysis of treatment effects in patients prescribed Ptx + VitE at our institution for the treatment of radiation necrosis (RN). Methods: A total of 48 patients treated with stereotactic radiosurgery (SRS) had evidence of RN and had MRI before and after starting Ptx + VitE. The radiation oncologist’s impression of the imaging in the electronic medical record was used to score response to treatment. Support Vector Machine (SVM) was used to train a model of radiomics features derived from radiation necrosis on pre- and 1st post-treatment T1 post-contrast MRIs that can classify the ultimate response to treatment with Ptx + VitE. Results: A total of 43.8% of patients showed evidence of improvement, 18.8% showed no change, and 25% showed worsening RN upon imaging after starting Ptx + VitE. The median time-to-response assessment was 3.17 months. Nine patients progressed significantly and required Bevacizumab, hyperbaric oxygen therapy, or surgery. Patients who had multiple lesions treated with SRS were less likely to show improvement (p = 0.037). A total of 34 patients were also prescribed dexamethasone, either before (7), with (16), or after starting (11) treatment. The use of dexamethasone was not associated with an improved response to Ptx + VitE (p = 0.471). Three patients stopped treatment due to side effects. Finally, we were able to develop a machine learning (SVM) model of radiomic features derived from pre- and 1st post-treatment MRIs that was able to predict the ultimate treatment response to Ptx + VitE with receiver operating characteristic (ROC) area under curve (AUC) of 0.69. Conclusions: Ptx + VitE appears safe for the treatment of RN, but randomized data are needed to assess efficacy and validate radiomic models, which may assist with prognostication.