Phoenix dactylifera L. pollen versus pentoxifylline on improvement of sperm parameters in idiopathic male infertility: A randomized clinical trial.

ETHNOPHARMACOLOGICAL RELEVANCE: Phoenix dactylifera L. pollen is the male reproductive dust of palm flowers known as a natural product that is considered a strong stimulant of sexual potency and fertility in Iranian traditional medicine (ITM). In this regard, no evidence-based medications are empirically prescribed to treat IMI. However, applying traditional medicine for the treatment of male infertility has attracted more attention in recent years. AIM OF THE STUDY: Phoenix dactylifera L. pollen was compared with pentoxifylline (PTX) to evaluate its efficacy on sperm parameters. MATERIALS AND METHODS: During this parallel randomized controlled trial, 80 adult men with asthenozoospermia, oligozoospermia, or teratozoospermia (age 20-35 years) were enrolled. In two separate groups of participants with a 1:1 ratio, participants received either 6 g of Phoenix dactylifera L. pollen powder daily or 400 mg of PTX tablets daily for 90 days. We measured the sperm parameters as well as the serum sex hormones in the sample. ANCOVA and t-tests were used to compare groups. RESULTS: There was no significant difference between the study groups in terms of baseline characteristics or demographic characteristics. According to the results, participants who took Phoenix dactylifera L. pollen powder had significantly improved sperm concentration (p = 0.016), morphology (p = 0.029), sperm counts (p = 0.012), progressive motility (p = 0.016), total motility (p = 0.018), and reduced immotile sperms (p = 0.014) compared to those who took PTX. CONCLUSIONS: In light of these results, Phoenix dactylifera L. pollen is recommended as a treatment factor for ameliorating IMI by enhancing sperm functional capacity and semen parameters.

Pentoxifylline attenuates nonalcoholic fatty liver by inhibiting hepatic macrophage polarization to the M1 phenotype.

BACKGROUND: Nonalcoholic fatty liver (NAFL), recognized as one of the most common causes of chronic liver diseases, is increasingly prevalent worldwide. Pentoxifylline, a derivative of theobromine extracted from Theobroma cacao and tea, has been studied for effects on blood viscosity, tissue oxygenation and inflammation. However, its effects on hepatic lipid accumulation and the potential mechanisms remain unclear. PURPOSE: This study aimed to investigate the therapeutic effects of pentoxifylline on high-fat diet-induced NAFL and to explore the corresponding molecular mechanisms. METHODS: NAFL mice were injected with or without 25, 50 or 100 mg/kg pentoxifylline for 2 weeks. Hepatic steatosis was observed by haematoxylin-eosin staining and Oil Red O staining, the levels of serum total cholesterol, triglyceride were detected by biochemical kits, and insulin resistance was evaluated by glucose and insulin tolerance tests. In addition, we measured the frequencies of macrophage and its polarization subsets in the liver using flow cytometry and immunofluorescence. The expressions of proteins associated with macrophage polarization signaling pathways were assessed by Western blotting and flow cytometry histograms. Molecular docking and cellular thermal shift assay were conducted to identify and verify the target protein of pentoxifylline in macrophage. RESULTS: Pentoxifylline significantly alleviated hepatic lipid accumulation, reduced blood lipid levels and improved insulin resistance. Strikingly, the excessive M1 macrophages in NAFL development was abolished by pentoxifylline. And pentoxifylline was further evidenced it failed to reduce hepatocyte lipid accumulation in the absence of macrophages in vitro. Mechanistically, pentoxifylline competed with LPS for binding to toll-like receptor 4, dramatically inhibiting the TLR4/MyD88/NF-κB signaling pathway. CONCLUSION: Pentoxifylline attenuated NAFL by inhibiting hepatic macrophage M1 polarization, indicating that pentoxifylline could be a therapeutic candidate for NAFL. This study first observed that M1 macrophages were increased in NAFL mice and then revealed the molecule targeted by pentoxifylline. In addition, we provided evidence that macrophage targeting may be an emerging strategy for NAFL treatment.

Combined atorvastatin and pentoxifylline in ameliorating inflammation induced by complete Freund's adjuvant.

Injection of complete Freund's adjuvant (CFA) into one of the footpads of Wistar rats promotes swelling in all the footpads (including non-injected footpads) in the next few days, indicating a complicated immunological reaction and autoimmune arthritis. This survey was performed to assess the synergistic benefits of combined atorvastatin and pentoxifylline for treating arthritis induced by CFA. Therapeutic regimes began on day 12 post-challenge when all the rats recorded an arthritis index of more than one and continued throughout the investigation until day 32. Treatment with combined atorvastatin and pentoxifylline at half doses led to synergistic benefits causing the regression of clinical and radiological appearance of arthritis in non-injected paws, which was more favorable than treatment with any medication alone at full doses. Moreover, the combined treatment led to a reduction in some inflammatory biochemical parameters, such as myeloperoxidase, nitric oxide, and C-reactive protein, which was more pronounced than those of the treatment with each medication alone. The mRNA expression of IL-1ß and TNF-α in the rat toe area was significantly decreased by combination therapy, and this reduction was more significant than that of monotherapy. The ratios of RORγc/T-bet, RORγc/GATA-3, RoRγc/Foxp3, T-bet/GATA-3, and T-bet/Foxp3 expression showed a further decrease in the combined treated group compared to other groups. Interestingly, combination therapy did not reduce T lymphocyte proliferation to a level lower than healthy rats. Overall, the combination of atorvastatin and pentoxifylline possesses immunomodulatory synergistic benefits, and this approach may be an impressive strategy to manage complicated inflammation.

A cryoprotectant supplemented with pentoxifylline can improve the effect of freezing on the motility of human testicular sperm.

This study examined the effect of a cryoprotectant with and without pentoxifylline supplementation on the motility and viability of human testicular sperm, both before and after freezing. Testicular samples were obtained from 68 patients with azoospermia who came to the Andrology Service of West China Second University Hospital, Sichuan University, for testicular biopsies from December 2019 to April 2020. All patients were assigned randomly to two groups: experimental, whose testicular sperm were added to the cryoprotectant with pentoxifylline, and the control, whose testicular sperm were added to the cryoprotectant without pentoxifylline. Both groups used the same freezing and thawing methods. Testicular sperm motility in the experimental group was significantly higher than that of the control group, both before and after cryopreservation. The recovery rate of sperm motility in the experimental group was significantly higher than that of the control group. The percentage of samples with motile testicular sperm in the experimental group was significantly higher than that of the control group after thawing. Sperm viability was unchanged between the experimental and control groups, both before and after freezing. Overall, a pentoxifylline-supplemented cryoprotectant can significantly improve the motility of testicular sperm before and after cryopreservation.

Potential usefulness of pentoxifylline, a non-specific phosphodiesterase inhibitor with anti-inflammatory, anti-thrombotic, antioxidant, and anti-fibrogenic properties, in the treatment of SARS-CoV-2.

Although most patients with coronavirus disease 2019 (COVID-19) have a good prognosis, in some cases, the disease progresses rapidly, and the mortality rate is high. Some evidence suggests that infection with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) produces a 'cytokine storm', which is related to acute respiratory distress syndrome or multi-organ dysfunction leading to physiological deterioration and death. It is important to highlight the state of hypercoagulability that can be triggered, involving microvascular thrombosis and vascular occlusive events, which are relevant to such poor outcomes. At present, no specific antiviral drug or vaccine is available for SARS-CoV-2 infection, and current research is aimed at preventing and mitigating damage to the target organs, mainly the lungs. In seeking therapies for patients with COVID-19, immunomodulators, cytokine antagonists and early anti-coagulation therapies have been tested in attempts to reduce the mortality rate. Pentoxifylline, a non-specific phosphodiesterase inhibitor widely used to improve the rheological properties of blood, has beneficial anti-inflammatory properties and can significantly reduce the serum levels of pro-inflammatory cytokines such as interleukin (IL)-6, IL-1, tumour necrosis factor-alpha, C-reactive protein and other immunoregulators. It has also been found to exert anti-thrombotic, antioxidant and anti-fibrogenic actions. These properties could help to prevent or mitigate the inflammatory response and hypercoagulability that develop with SARS-CoV-2 infection, decreasing multi-organ dysfunction manifesting primarily as acute lung injury.

Pentoxyfilline as a treatment for subcorneal pustular dermatosis.

Subcorneal pustular dermatosis (SPD) is a rare pustular neutrophilic dermatosis in which groups of sterile pustules appear in the superficial (subcorneal) skin. This chronic condition can be associated with significant morbidity and decreased quality of life. Dapsone is the first-line therapy for SPD, but some patients fail to respond or cannot tolerate it. In these instances, patients may be treated with second-line therapies such as phototherapy, topical corticosteroids, or systemic agents including glucocorticoids, acitretin, immunosuppressive, or biologic medications. These therapies may not always be efficacious and can be associated with intolerable adverse effects. Here, we report a case of a patient who sustained long-term remission and no side effects with the novel use of pentoxifylline, a tumor necrosis factor-alpha inhibitor, as monotherapy. Pentoxifylline should be considered as a possible therapy in patients with SPD intolerant to dapsone.

Influence of inflammatory disorders on pharmacokinetics of lisofylline in rats: implications for studies in humans.

1. Despite the number of favourable properties of lisofylline (LSF), clinical trials on this compound have not yielded the expected results yet. 2. The aims of this study were to evaluate the pharmacokinetics of LSF enantiomers in rats following intravenous, oral and subcutaneous administration of (±)-LSF and to assess the influence of experimental inflammatory disorders, such as multiple organ dysfunction syndrome and severe sepsis on LSF pharmacokinetics. 3. In addition, based on the results obtained an attempt was made to elucidate the possible reasons for the failure of LSF therapy in clinical trials carried out in patients with severe inflammatory disorders. 4. A subcutaneous route of (±)-LSF administration to rats is more favourable than an oral one due to a high bioavailability and a fast absorption of both LSF enantiomers. Pharmacokinetics of LSF in rats is significantly influenced by inflammatory diseases. Too low LSF serum levels might have been one of the reasons for clinical trial failures. A long-term i.v. infusion of LSF seems to be more effective compared to short-term multiple infusions that were used in clinical trials, as it may provide concentrations above IC50 for inhibition of both TNF-alpha release and cAMP degradation in serum for a longer period of time.

Supplementation of biotin to sperm preparation medium enhances fertilizing ability of spermatozoa and improves preimplantation embryo development.

PURPOSE: Motility of spermatozoa helps not only in planning the type of infertility treatment but also directly reflects the success rate in assisted reproductive technology (ART). Previously, biotin, a water-soluble vitamin, has been shown to increase the motility and longevity of cryopreserved human spermatozoa. The present study was designed to understand the molecular basis of the beneficial effects of presence of biotin in sperm wash medium on early embryo development. METHODS: The effect biotin supplementation to sperm wash medium on the sperm parameters were assessed in swim-up fraction of normozoospermic and asthenozoospermic ejaculates collected from infertile men. Fertilization and early embryo development was studied using Swiss albino mice. RESULTS: Even though both biotin and pentoxifylline (PTX) enhanced the motility of spermatozoa from normozoospermic and asthenozoospermic samples, biotin group exhibited higher in vitro survival. Using mouse model, we observed that presence of biotin or PTX in sperm wash medium improved the fertilization rate and blastocyst rate compared to control. Blastocysts from these groups had significantly higher total cell number (P < 0.01) and lower apoptotic index. In silico target prediction revealed that GTPase HRas (HRas), tyrosine-protein phosphatase nonreceptor type 1 (PTP1B), and glucokinase are the probable targets for biotin. Solution-state Nuclear Magnetic Resonance (NMR) studies confirmed that biotin interacts both with human HRas and PTP1B. CONCLUSION: Our results indicate that presence of biotin in sperm wash medium can improve the fertilization potential and preimplantation embryo development and can be considered as a safe alternate to PTX.

Comparative evaluation of the effects of Withania somnifera with pentoxifylline on the sperm parameters in idiopathic male infertility: A triple-blind randomised clinical trial.

In this triple-blind randomised clinical trial, we compared the effects of Withania somnifera and pentoxifylline on the sperm parameters in idiopathic male infertility. One hundred infertile male patients were randomly allocated into either W. somnifera or pentoxifylline groups. Patients in the herbal group received six capsules containing 5 g/daily of W. somnifera root, and subjects in the pentoxifylline group received six capsules containing 800 mg/daily of pentoxifylline and placebo for 90 days. Sperm parameters were analysed at the beginning and end of the study. W. somnifera increased mean sperm count (12.5%) and progressive motility (21.42%) and improved sperm morphology (25.56%) compared to the baseline (p = .04, p = .001 and p = .000 respectively). Moreover, pentoxifylline increased mean semen volume (16.46%), progressive motility (25.97%) and improved sperm morphology (13.28%) versus the baseline (p = .02, p = .003 and p = .01 respectively). Intergroup comparison showed no significant differences between the two groups regarding semen volume (p = .11), sperm count (p = .09), morphology (p = .12) and progressive motility (p = .77) after treatment. No major complication was reported in either of the two groups. W. somnifera, a traditional medicine remedy, improves sperms parameters in idiopathic male infertility without causing adverse effects. Therefore, this medication can be considered to be an alternative to pentoxifylline in this regard.

Involvement of cAMP/EPAC/Akt signaling in the antiproteolytic effects of pentoxifylline on skeletal muscles of diabetic rats.

Advances in the knowledge of the mechanisms controlling protein breakdown in skeletal muscles have allowed the exploration of new options for treating muscle-wasting conditions. Pentoxifylline (PTX), a nonselective phosphodiesterase (PDE) inhibitor, attenuates the loss of muscle mass during catabolic conditions, mainly via inhibiting protein breakdown. The aim of this study was to explore the mechanisms by which PTX inhibits proteolysis in the soleus and extensor digitorum longus (EDL) muscles of streptozotocin-induced diabetic rats. The levels of atrogin-1 and muscle RING finger-1 were decreased, as were the activities of caspase-3 (EDL) and calpains (soleus and EDL), in diabetic rats treated with PTX, which at least partly explains the drop in the ubiquitin conjugate (EDL) levels and in proteasome activity (soleus and EDL). Treatment with PTX decreased PDE activity and increased cAMP content in muscles of diabetic rats; moreover, it also increased both the protein levels of exchange protein directly activated by cAMP (EPAC, a cAMP effector) and the phosphorylation of Akt. The loss of muscle mass was practically prevented in diabetic rats treated with PTX. These findings advance our understanding of the mechanisms underlying the antiproteolytic effects of PTX and suggest the use of PDE inhibitors as a strategy to activate cAMP signaling, which is emerging as a promising target for treating muscle mass loss during atrophic conditions. NEW & NOTEWORTHY cAMP signaling has been explored as a strategy to attenuate skeletal muscle atrophies. Therefore, in addition to ß2AR agonists, phosphodiesterase inhibitors such as pentoxifylline (PTX) can be an interesting option. This study advances the understanding of the mechanisms related to the antiproteolytic effects of PTX on skeletal muscles of diabetic rats, which involve the activation of both exchange protein directly activated by cAMP and Akt effectors, inhibiting the expression of atrogenes and calpain/caspase-3-proteolytic machinery.

Comparison and evaluation of capacitation and acrosomal reaction in freeze-thawed human ejaculated spermatozoa treated with L-carnitine and pentoxifylline.

Cryopreservation is used to preserve the spermatozoa; however, it leads to a reduction in sperm quality. L-carnitine (LC) influences sperm motility and preserves the sperm membrane and DNA integrity. The objectives of this study were to evaluate the protective effects of LC on the membrane integrity of normal human spermatozoa and compare it with pentoxifylline (PT) during cryopreservation. Thirty normal semen samples, prepared by swim-up procedure, were divided into three aliquots: a control without any treatment and two experimental aliquots that were incubated in PT or LC for 30 min. All aliquots were cryopreserved and thawed after 48 hr. To evaluate the percentages of intact, acrosomal-reacted and capacitated spermatozoa, lectin histochemistry and flow cytometry were performed by wheat germ agglutinin, peanut agglutinin and Con A. Statistical analyses were performed using ANOVA. LC supplementation elevated the percentage of noncapacitated spermatozoa compared with control and PT-treated samples and the percentages of acrosomal intact spermatozoa compared with PT-treated samples. PT pre-treatment improved the motility but not membrane integrity. LC supplementation reduced the percentages of acrosomal-reacted spermatozoa compared with the control and PT-treated samples. Although LC did not improve motility, it protected the plasma membrane and acrosomal integrity. Therefore, LC may be the superior choice compared to PT for maintaining the sperm integrity.

The susceptibility to autoxidation of erythrocytes in diabetic mice: Effects of melatonin and pentoxifylline.

Oxidative stress had a great importance in development of complications in diabetes. We investigated effects of melatonin and pentoxifylline in diabetic mice. Swiss albino mice (n = 40) were divided into four groups: alloxan-induced diabetes mellitus (DM), alloxan-induced diabetes with melatonin supplementation (DM + MLT), alloxan-induced diabetes with pentoxifylline supplementation (DM + PTX), and control. Glutathione-peroxidase (GSH-Px) activity, malondialdehyde (MDA) and reduced glutathione (GSH) levels, and susceptibility to oxidation of erythrocytes were measured. MDA levels were higher than control in the DM and DM + MLT. The DM had more MDA level than the DM + MLT and DM + PTX (P < 0.001). After in vitro oxidation, MDA levels of all groups were found higher than the control. However, they were significantly lower than the DM in DM + PTX and DM + MLT (P < 0.001). Although GSH levels of the DM and DM + PTX were less than the control, GSH-Px activity of the DM was lower than the control and DM + PTX (P < 0.05). We suggest that there is increased oxidative stress and compromised antioxidant status of erythrocytes in diabetes; however, it can be effectively prevented by melatonin or pentoxifylline supplementation.

Evaluation of the protective effect of pentoxifylline on carrageenan-induced chronic non-bacterial prostatitis in rats.

Chronic non-bacterial prostatitis (CNP) is the most common type of prostatitis and oxidative stress (OS) was shown to be highly elevated in prostatitis patients. This study aimed to investigate the protective effect of pentoxifylline (PTX) on CNP induced by carrageenan in rats. Male adult Wistar rats (n = 30) were divided into control, CNP and three treatment groups (n = 6) including CNP + cernilton and CNP + PTX groups. CNP was induced by single intraprostatic injection of 1% carrageenan (100 µl). Rats in treatment groups received orally cernilton 100 mg/kg and PTX at 50 and 100 mg/kg 1 week after CNP induction for 21 days. Prostatic index (PI), prostatic specific antigen (PSA), tumor-necrosis factor alpha (TNF-α), serum lipid peroxidation (MDA), blood urea nitrogen, creatinine and histopathological changes were compared between groups. There were significant increase of PI, serum levels of PSA, TNF-α and MDA in CNP group at 29 day. In treatment groups, significant reduction in PI, serum levels of PSA, TNF-α, MDA and creatinine was observed especially in rats treated with dose of 50 mg/kg of PTX. In CNP group, histopathological changes of the prostate such as leucocyte infiltration, large involutions and projection into the lumen and reducing the volume of the lumen were observed as well. Whereas PTX, especially at dose of 50 mg/kg, could improve the above-mentioned changes remarkably in CNP treated rats. For the first time, our findings indicated that PTX improved CNP induced by carrageenan in rats.

Pentoxifylline besides naltrexone recovers morphine-induced inflammation in male reproductive system of rats by regulating Toll-like receptor pathway.

This study aimed to investigate the effect of pentoxifylline on complications of prolonged usage of morphine upon the testis and sperm parameters of rats. In this study, forty male Wistar rats were divided into five groups (n = 8) and treated for 56 days to only saline, only morphine, only pentoxifylline, pentoxifylline + morphine and naltrexone + morphine. The diameters of seminiferous tubules, the maturity of germ line epithelium and sperm parameters were evaluated. The expression of inflammatory-related factors in testis tissues were also investigated at gene and protein levels. The data were calculated by one-way ANOVA test followed by Tukey's post hoc test using SPSS software for windows (version 20). Seminiferous tubule diameter, the maturity of spermatogonia and sperm parameters were significantly decreased in morphine group in comparison with control, pentoxifylline and pentoxifylline + morphine groups (p < .001). The expression of anti-inflammatory markers, at both gene and protein levels, was significantly increased in testis of morphine-treated rats in comparison with other groups (p < .001). Chronic morphine administration induces destructive effects on male reproductive system by regulating inflammatory responses. Pentoxifylline recovers the destructive effects of morphine on male reproductive system by inhibiting TLR (Toll-like receptor) activity, as an anti-inflammatory response.

Pentoxifylline and its active metabolite lisofylline attenuate transforming growth factor ß1-induced asthmatic bronchial fibroblast-to-myofibroblast transition.

Bronchial asthma is characterized by persistent airway inflammation and airway wall remodeling. Among many different cells and growth factors triggering changes in bronchi structure, transforming growth factor ß1-induced fibroblast to myofibroblast transition is believed to be very important. The aim of this study was to evaluate whether theophylline (used in asthma therapy) and two other methylxanthines (pentoxifylline and its active metabolite lisofylline), may affect transforming growth factor ß1-induced fibroblast to myofibroblast transition in bronchial fibroblasts derived from asthmatic patients. We show here for the first time that selected methylxanthines effectively reduce transforming growth factor ß1-induced myofibroblast formation in asthmatic bronchial fibroblast populations. PTX was found to be the most effective methylxanthine. The number of differentiated myofibroblasts after PTX, LSF and THEO administration was reduced at least twofold. Studies on the use of methylxanthines opens a new perspective in the development of novel strategies in asthma therapy through their two-pronged, anti-inflammatory and anti-fibrotic action. In the future they can be considered as promising anti-fibrotic drugs.

Neuroprotective effects of p-tyrosol after the global cerebral ischemia in rats.

BACKGROUND: Salidroside is a biologically active compound derived from Rhodiola rosea L. Studies showed that salidroside after i.v. injection is extensively metabolized to p-tyrosol and only trace amounts of salidroside are found in the brain tissue. OBJECTIVE: The aim of the study was to investigate the neuroprotective effects of p-tyrosol in the global cerebral ischemia-reperfusion (GCI) model. STUDY DESIGN: A total of 103 Wistar rats were assigned to groups of sham-operated (n=10), control (n=42), p-tyrosol-treated (n=36), and pentoxifylline-treated (n=15) animals. The rats of control, p-tyrosol-treated, and pentoxifylline-treated groups received intravenously 0.9% NaCl solution, 2% solution of p-tyrosol in doses of 5mg/kg, 10mg/kg, and 20mg/kg, and pentoxifylline in a dose of 100mg/kg, respectively, daily for 5 days. Rats were examined at days 1, 3, and 5 after GCI. After evaluation of neurological deficit, animals were euthanized for morphological and biochemical characterization. METHODS: Rats of control, p-tyrosol-treated, and pentoxifylline-treated groups were exposed to three-vessel model of GCI. Neurological deficit, numeric density of neurons in hippocampal CA1 region, and percentage of neurons with focal and total chromatolysis were studied. Biochemical study assessed contents of conjugated dienes and fluorescent products in brain homogenate. RESULTS: In control group, only 50.0% of rats survived by day 5 after the GCI; 38.1% of survived animals had severe neurologic deficit. In brain tissue of PTX-treated rats, the levels of diene conjugates and fluorescent products were 79% and 73%, respectivley, at day 5 compared with control. Differences in diene conjugates were statistically significant compared with control. The survival rate of animals treated with 20mg/kg p-tyrosol was 82.3% at day 5 after GCI. In p-tyrosol-treated GCI rats, the numeric density of neurons in the hippocampal CA1 region was higher by 31% compared with control. The percentage of neurons with focal and total chromatolysis decreased by 27% and 43%, respectively. At day 5 after GCI, the levels of conjugated dienes and fluorescent products were significantly lower (by 37% and 45%, respectively) in group of animals treated with 20mg/kg p-tyrosol compared with control. Moderate neuroprotective effects of 5mg/kg p-tyrosol administration were documented only at day 5 after GCI. In case of 10mg/kg p-tyrosol administration, neuroprotection was documented sooner: at day 1 or 3 after GCI. However, administration of 5 and 10mg/kg p-tyrosol did not affect animal survival. CONCLUSION: Course administration of intravenous p-tyrosol in a dose of 20mg/kg increased survival, reduced neurological deficit after GCI, attenuated neuronal damage in the hippocampus, and attenuated lipid peroxidation in brain tissue in animals subject to GCI with reperfusion.

Increased level of reactive oxygen species persuades postovulatory aging-mediated spontaneous egg activation in rat eggs cultured in vitro.

The present study was aimed to find out whether increased level of reactive oxygen species (ROS) particularity hydrogen peroxide (H2O2) could persuade postovulatory aging-mediated abortive spontaneous egg activation (SEA) in rat eggs cultured in vitro. For this purpose, ROS and H2O2 levels, mitochondria distribution and its membrane potential, p286-CaMK-II, Emi2, Thr-161 phophorylated cyclin-dependent protein kinase1 (Cdk1) as well as cyclin B1 levels, in vitro effects of 3-tert-butyl-4 hydroxy anisole (BHA), pentoxifylline and dibutyryl-adenosine 3',5'-cyclic monophosphate (db-cAMP) were analyzed during postovulatory aging-induced abortive SEA in vitro. Data of the present study suggest that postovulatory aging increased H2O2 levels, disturbed mitochondrial distribution pattern and mitochondrial membrane potential (MMP) in eggs. There was an significant increase of p286-CaMK-II level, while Emi2 level reduced significantly during egg aging in vitro. The reduced Emi2 level was associated with decreased Thr-161 phosphorylated cyclin-dependent kinase-1 (Cdk1) as well as cyclin B1 level in aged eggs that underwent abortive SEA. Further, supplementation of pentoxifylline, db-cAMP, and BHA protected postovulatory aging-mediated abortive SEA in concentration-dependent manner. These data suggest that postovulatory aging increased H2O2 levels, reduced MMP, and increased p286-CaMK-II. The increased p286-CaMK-II was associated with reduced Emi2 level and maturation-promoting factor levels during postovulatory aging-mediated abortive SEA. Drugs that elevate cAMP directly or indirectly and BHA protected postovulatory aging-mediated abortive SEA possibly by reducing ROS level in rat eggs cultured in vitro.

Pentoxifylline Accelerates Wound Healing Process by Modulating Gene Expression of MMP-1, MMP-3, and TIMP-1 in Normoglycemic Rats.

BACKGROUND: Although numerous recent advances in wound healing have highlighted the importance of adjunct therapies in maximizing healing potential, abnormal wound healing continues to cause significant expense, morbidity, and mortality. OBJECTIVE: This study examines the effects of pentoxifylline (PTX) on wound healing. HYPOTHESIS: We are expecting that PTX administration can increase biomechanical parameters and modulate matrix metalloproteinaseses-1 (MMP-1) and MMP-3, and matrix metalloproteinase inhibitor-1 (TIMP-1) in normoglycemic (NG) rat model of wound healing. METHODS: Each rat received an identical wound from a full-thickness incision on its back. Experimental rats received systemic administration of PTX. All rats underwent examinations for biomechanical and polymerase chain reaction(PCR) analysis. Maximum stress and energy absorption were calculated as the biomechanical examinations. Expressions of MMP-1, MMP-3 and TIMP-1 genes were evaluated semi-quantitatively by reverse transcriptional (RT)-PCR. RESULTS: PTX significantly improved biomechanical parameters. Quantification of MMP-1, MMP-3, and TIMP-1 showed that PTX significantly reduced gene expressions of MMP-1 and MMP-3. There was a significant increase in TIMP-1 gene expression. CONCLUSION: Systemic administration of PTX significantly accelerated the wound healing process in NG rats.

[Effectiveness of pentoxifylline and of bio-electromagnetic therapy in lower limb obliterative arterial disease]. / A pentoxifillin és a bioelektromágnes-regulációs kezelés hatása alsó végtagi obliteratív veroérbetegségben.

INTRODUCTION: There are limited therapeutic options to improve microcirculation. AIM: The question of the study was to investigate any potential beneficial effect of bio-electro-magnetic-regulation therapy on microcirculation in patients suffering from obliterative peripheral arterial disease including the circulation of lower extremities, as well as intermittent claudication. METHOD: Thirty patients suffering from obliterative peripheral arterial disease (Fontaine IIa and IIb) were recruited. The first step of the study was to determine the pain free and maximal walking distance with a treadmill unit. After the placebo period patients received 8 and 20 minutes bio-electro-magnetic-regulation treatment 16 times. After the treatment the pain free and maximal walking distance were measured again. In the second stage of the study the patients were treated by pentoxifylline infusions. RESULTS: Bio-electro-magnetic-regulation treatment increased the pain free period by 57.4% (p = 0.005) and the maximal walking distance by 36.6% (p = 0.042). The two forms of therapy together increased the pain free and maximal walking distance by 81.9% and by 84.0%, respectively. The combined therapy was very effective in contrast to placebo and bio-electro-magnetic-regulation treatment (p = 0.000373 and p = 0.00741, respectively). CONCLUSIONS: The bio-electro-magnetic-regulation therapy mainly affected the microvessels and pentoxifylline therapy rather had beneficial effects on hemorheology. The clinical effectiveness of combined therapy was good or excellent in 70% of patients.