Effect Of Pentoxifylline Research Articles

Surgery-Induced Changes in Erythrocyte and Plasma Lipid Peroxidation, Enzymatic and Non-Enzymatic Antioxidants of Female Rats: Protective Role of Heparin and Pentoxifylline

Background: Intra abdominal adhesions are a complication that occurs after many abdominal surgical procedures, especially gynecological operations. These complications occur by irritating the peritoneum due to such circumstances as infection or surgical trauma, and are considered a pathological part of the healing process of peritoneal injury. It manifests itself with symptoms such as pain, intestinal or urethral obstruction and abdominal abscesses. Oxidative stress due to adhesions plays an important role on adhesion formation. In addition to many researches done at the point of prevention of adhesion and decreasing stress parameters, in this study, it was planned to determine the effect of Heparin (H) and Pentoxifylline (PTX) on malondialdehyde (MDA) and some antioxidant values.Materials, Methods & Results: This study was performed on rats and thirty-seven female Sprague-Dawley rats were randomized into four groups. The first group was sham (Sh) group (n = 7) and laparotomy was performed and 2 mL of 0.9 % NaCl was applied. For all other rats (n = 30) the small intestine was withdrawn and the uterus was uncovered and the anti mesenteric surfaces of the left uterine horn and left abdominal wall were superficially tilted until slight bleeding was seen. Lesion areas have been covered. Two mL 0.9 % NaCl to control (C) group (n = 10), 500 IU heparin to group H, and 25 mg / kg Pentoxifylline to group PTX (n = 10) have been given and then the abdominal incision was closed. The adhesion score of group Sh was found to be more important than C and PTX groups (P < 0.05). The adhesion score of group C was determined to be more significant than group H (P < 0.05). In group Sh, erythrocyte reduced glutathione (GSH) levels were found to be more significant (P < 0.01) than C, H and PTX groups whereas it was found that group C was more significant than group H (P < 0.01). In group Sh, glutathione peroxidase (GSH-Px) activity was found to be more significant (P < 0.05) than H and PTX groups, while MDA level was found to be lower and more significant (P < 0.01) than group C. In addition, group C was found to be higher and more significant (P < 0.01) than group H. Plasma vitamin E levels in Sh, H and PTX groups were found to be higher and more significant (P < 0.01) than group C. It is also observed that MDA levels in group C are higher and more significant (P < 0.01) than all groups. Nitric oxide (NO) level in Sh group was found to be lower and more significant (P < 0.05) than the other groups whereas it is determined that NO level in H group is higher and more significant (P < 0.05) than group C. Activites of erythrocyte catalase (CAT) and superoxide dismutase (SOD), the levels of plasma vitamin A and β-carotene were not important in all groups.Discussion: Intra abdominal adhesions that occur due to operations performed in the abdominal region still remain as a major problem. This adhesion brings certain problems with itself. Various applications have been made to reduce these problems. In this study, it was observed that inhibition of heparin and pentoxifylline adhesions contributed to the reduction of MDA levels and the reduction of oxidative damage due to the increase in levels of Vitamin E, GSH, GSH-Px and NO levels. In conclusion, it is suggested that heparin and pentoxifylline should be used to prevent adhesions due to abdominal operations and to reduce oxidative damage.

Pentoxifylline Alone or in Combination with Gentamicin or Vancomycin Inhibits Live Microbe-Induced Proinflammatory Cytokine Production in Human Cord Blood and Cord Blood Monocytes In Vitro.

Neonatal sepsis and its accompanying inflammatory response contribute to substantial morbidity and mortality. Pentoxifylline (PTX), a phosphodiesterase inhibitor which suppresses transcription and production of proinflammatory cytokines, is a candidate adjunctive therapy for newborn sepsis. We hypothesized that PTX decreases live microbe-induced inflammatory cytokine production in newborn blood. Cord blood was stimulated with live microorganisms commonly encountered in newborn sepsis (Escherichia coli, Staphylococcus aureus, Staphylococcus epidermidis, or Candida albicans) and simultaneously treated with antimicrobial agents (gentamicin, vancomycin, or amphotericin B) and/or clinically relevant concentrations of PTX. Microbial colony counts were enumerated by plating, supernatant cytokines were measured by multiplex assay, intracellular cytokines and signaling molecules were measured by flow cytometry, and mRNA levels were measured by quantitative reverse transcription-PCR. PTX inhibited concentration-dependent E. coli-, S. aureus-, S. epidermidis-, and C. albicans-induced tumor necrosis factor (TNF) and E. coli-induced interleukin-1β (IL-1β) production in whole blood, with greater suppression of proinflammatory cytokines in combination with antimicrobial agents. Likewise, PTX suppressed E. coli-induced monocytic TNF and IL-1β, whereby combined PTX and gentamicin led to significantly greater reduction of TNF and IL-1β. The anti-inflammatory effect of PTX on microbe-induced proinflammatory cytokine production was accompanied by inhibition of TNF mRNA expression and was achieved without suppressing the production of the anti-inflammatory IL-10. Of note, microbial colony counts in newborn blood were not increased by PTX. Our findings demonstrated that PTX inhibited microbe-induced proinflammatory cytokine production, especially when combined with antimicrobial agents, without enhancing microbial proliferation in human cord blood in vitro, thus supporting its utility as candidate adjunctive agent for newborn sepsis.

Electrochemiluminescence sensor for pentoxifylline detection using Au nanoclusters@graphene quantum dots as an amplified electrochemiluminescence luminophore

The Au nanoclusters@graphene quantum dots nanocomposite as an electrochemiluminescence (ECL) luminophore was synthesized through amide coupling reaction between Au nanoclusters (Au NCs) and graphene quantum dots (GQDs). The ECL intensity of the as-prepared Au NCs@GQDs was enhanced for 2.6-fold compared with that of Au NCs or 40-fold compared with that of GQDs, which was due to the ECL resonance energy transfer between GQDs as a donor and Au NCs as an acceptor, and excellent electrical conductivity of GQDs. In addition, the synergistic effect likewise improved stability of the ECL signal. A type of “signal-off” solid-state ECL sensor for detection of pentoxifylline was fabricated based on the selective quenching effect of pentoxifylline on the ECL signal of Au NCs@GQDs in alkaline medium. The sensor showed excellent sensitivity and wide linearity for pentoxifylline determination in the range from 7.0 × 10−7 to 1.2 × 10-4 mol/L with the detection limit of 9.0 × 10-8 mol/L (S/N = 3). The proposed method was successfully applied for pentoxifylline detection in pharmaceutical tablet with satisfactory results.

The Effects of Oxygen and Treatments in Hypoxic Conditions in SH-SY5Y Cells.

Many patients are admitted to the emergency department due to trauma. Patients with massive hemorrhage and respiratory failure can fall into hypovolemic shock. Thereafter, oxygen is an essential part of the treatment of trauma patients, but the mechanisms of its effects in the management of trauma patients remain unknown. Therefore, we conducted an experiment to apply hypoxia, hyperoxia, and other treatment with the goal of decreasing hypoxic neuronal cells damage, as reflected by cell survival, apoptosis, hydrogen peroxide (H2O2) production, and hypoxia-inducible factor 1α (HIF) expression in SH-SY5Y cells. Under hypoxic insults, cell survival percentages decreased and apoptosis was seen with increased necrotic cell death. High-pressure oxygen (80% O2) had no effect compared with normal-pressure oxygen (20% O2). After exposure to hypoxia, H2O2 production and levels of HIF significantly increased compared with normoxia. However, when pentoxifylline (PTX), steroid, and hypertonic saline (HTS) were added after exposure to hypoxic conditions, the production of H2O2 and HIF levels significantly decreased in the groups treated with PTX and HTS. That is, the neuroprotective effect of PTX and HTS alleviated the impacts of hypoxic insulted on neuronal cells.

Ratlarda Pentoksifilinin Kontrast Nefropatisi Üzerine Koruyucu Etkileri

Ratlarda Pentoksifilinin Kontrast Nefropatisi Üzerine Koruyucu Etkileri

Inhibitory effects of pentoxifylline on inflammation-related tumorigenesis in rat colon

Chronic inflammation in the colorectum increases the risk of colorectal cancer development. Pentoxifylline, a medicine used for improving the circulation, has been reported to inhibit TNF-α production and to ameliorate inflammatory bowel disease and non-alcoholic steatohepatitis. In this study, we investigated the effects of pentoxifylline on inflammation-related colon tumorigenesis in a rodent model using Kyoto APC delta rats, which have APC mutation and are susceptible to colon carcinogenesis. Male Kyoto APC delta rats were treated with azoxymethane and dextran sodium sulfate, and were subsequently administered water, with or without pentoxifylline. At the end of the experiment, the development of colorectal tumor was significantly inhibited in the pentoxifylline group. The pentoxifylline treatment also lowered the levels of oxidative stress markers and mRNAs of pro-inflammatory cytokines, including TNF-α and IL-6, in the colon mucosa. The PCNA labeling index and the inflammation score were also decreased in the colon of rats in the pentoxifylline -treated group. We also used an endoscopy to observe the tumor progression and inflammation in the colon of rats, revealing that inflammation grade was significantly lower in pentoxifylline-treated group at several points during the experiment. These findings suggest that pentoxifylline treatment might be useful for chemoprevention of inflammation-related colon cancer.

Potential therapeutic roles of 10-dehydrogingerdione and/or pentoxifylline against calcium deposition in aortic tissues of high dietary cholesterol-fed rabbits.

The present study aimed to investigate the inhibitory effects of 10-dehydrogingerdione (10-DHGD) and pentoxifylline (PTX) either individually or in combined form on calcium deposition in high cholesterol diet (HCD)-fed rabbits as compared to atorvastatin (ATOR), and to clarify the underlying mechanisms. Three-months-old male New Zealand white rabbits received either normal chow or HCD for 12weeks. The latter group was subdivided into five groups and concurrently treated either with vehicle (dyslipidemic control), ATOR, 10-DHGD, PTX or combined 10-DHGD and PTX. Blood samples and aortic tissue were collected for biochemical and histological analyses. HCD-fed rabbits displayed dyslipidemia, inflammation, atherosclerotic lesions, and calcium deposition in aortas as compared to normal group. This was associated with up-regulation of bone morphogenetic protein-2 (BMP-2), wingless-type MMTV integration site family 3A (Wnt3a) mRNA levels and osteopontin expression in their aortic tissue, along with higher serum alkaline phosphatase and osteocalcin levels. Furthermore, a marked decrease in osteoprotegerin, along with a significant increase in receptor activator of NF-κB(RANK) levels, was found in aortic tissue of dyslipidemic rabbits. 10-DHGD and PTX monotherapy significantly modulated the afore-mentioned calcification markers and attenuated aortic calcification to greater extent than ATOR. Combination of 10-DHGD and PTX exerted more anti-calcifying effect than either individual drug. Our findings suggested therapeutic roles of 10-DHGD and PTX against aortic calcium deposition in dyslipidemic rabbits, likely mediated by HDL-raising effect and attenuation of associated inflammation. Combination of 10-DHGD and PTX may represent a promising therapeutic strategy for aortic calcification associated with atherosclerosis.

Pentoxifylline protects against loss of function and renal interstitial fibrosis in chronic experimental partial ureteral obstruction

Tubulointerstitial fibrosis (TIF) is a hallmark of chronic kidney disease resulting from diverse etiologies and predicts severity and progression of the kidney disease. To investigate the pathogenesis of TIF, complete unilateral ureteral obstruction (UUO) is the most widely used animal model. However, UUO precludes evaluation of renal function. In the present study, we created a rat model of chronic partial ureteral obstruction (PUO), which allowed assessment of renal function at different intervals after obstruction. We examined the effects of pentoxifylline (PTF), a phosphodiesterase inhibitor used clinically to treat peripheral artery disease, on renal function and TIF. Studies were performed in sham-PUO rats and rats with 14-day PUO or 30-day PUO receiving vehicle in drinking water or PTF (400 mg/liter in drinking water). At day-14 PUO, glomerular filtration rate (GFR) was markedly and similarly depressed in rats receiving vehicle or PTF as compared with sham-operated rats. However, at day-30 PUO, GFR in rats receiving PTF was significantly higher than that in rats receiving vehicle, approaching the level seen in the sham-operated rats. At day-30 PUO, histologic studies also revealed a marked reduction of TIF in rats treated with PTF as compared with the rats receiving vehicle in drinking water. Western blot analysis demonstrated that at day-30 the expression of α-smooth muscle actin (an indicator of renal fibrosis) in the medulla was significantly reduced in PUO rats treated with PTF. In conclusion, PTF treatment ameliorated renal fibrosis and helped preserve renal function in a rodent model of PUO.

Topical pentoxifylline for pressure ulcer treatment: a randomised, double-blind, placebo-controlled clinical trial.

To evaluate the effectiveness of topical pentoxifylline (PTX) on pressure ulcer (PU) healing in critically ill patients. In this randomised, double blind, placebo-controlled clinical trial, patients with category I or II PUs were randomly assigned to receive either topical PTX 5% or a placebo twice daily for 14 days. Changes in PU characteristics (category and size) were assessed. The category of the PU was determined by the Stirling Pressure Ulcer Severity Scale (two-digit) at baseline (day zero), day seven and day 14 of treatment. PU length and width was measured with a disposable ruler and expressed as cm2. A total of 112 adult patients were enrolled in the study. Median PU size and score at day zero were 32 (10.00-69.33)cm2 and 1(1.00-2.00) respectively. In the PTX group, the mean differences (95% confidence interval, CI) of all PU scores and sizes decreased significantly across the intervals (day seven versus day zero, day 14 versus day zero, and day 14 versus day seven), compared with the placebo group Conclusion: The severity and size of PUs improved significantly in patients who received topical PTX 5% ointment twice a day for 14 days compared with those in the placebo group. Topical PTX may be considered as a potential option in the treatment of categories I and II PUs in critically ill patients.

Protective effect of pentoxifylline on amikacin-induced ototoxicity.

We conducted an animal experiment to assess the effect of adding pentoxifylline to amikacin to prevent amikacin-induced ototoxicity. This research was conducted on 24 rats arranged in four groups of 6. One group was injected with 200 mg/kg of intramuscular amikacin once daily for 14 days (AMK-only group). Another received 25 mg/kg of oral pentoxifylline and 200 mg/kg of intramuscular amikacin once daily for 14 days (PTX-AMK 14/14 group). A third group received 25 mg/kg of oral pentoxifylline for 28 days and 200 mg/kg of intramuscular amikacin once daily for 14 days on days 15 through 28 of the pentoxifylline regimen (PTX-AMK 28/14 group). Finally, a control group was administered 1 ml/day of 0.5% carboxymethyl cellulose for 28 days. Transient otoacoustic emissions (TOAEs) were statistically analyzed and serum urea and creatinine levels were measured before and after treatment. We found no significant differences in TOAEs among the groups at the study's onset, but after the experiment, TOAEs disappeared in all frequency bands in the AMK-only and PTX-AMK 14/14 groups. However, TOAEs were preserved in the PTX-AMK 28/14 group. In addition, the serum urea and creatinine levels in the PTX/AMK 28/14 group were significantly lower than the levels in the other two treatment groups (p < 0.05 for all), but not significantly different from those of the control group. We conclude, therefore, that 28 days of pentoxifylline treatment exerted a protective effect against amikacin-induced ototoxicity in rats.

Protective effects of pentoxifylline in small intestine after ischemia–reperfusion

ObjectiveThis study was performed to determine the healing effects of pentoxifylline on molecular responses and protection against severe ischemic damage in the small intestine.MethodsThirty-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 C1, P1, and P3 groups, respectively, 60 minutes before ischemia and to the rats in the C2, P2, and P4 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.ResultsAll 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.ConclusionsThe protective effects of pentoxifylline were confirmed by molecular responses and histopathological examination.

Protective effect of pentoxifylline on oxidative renal cell injury associated with renal crystal formation in a hyperoxaluric rat model.

The aim of the study is to investigate the effects of pentoxifylline (PTX) on the renal tubular cell injury and stone formation in a hyperoxaluric rat model induced by ethylene glycol and its possible underlying mechanisms. The study was performed with 30 male Wistar rats and randomized into three groups of teen. The sham-control (group 1) received only drinking water orally. The EG/untreated (group 2) received drinking water containing 0.75% EG for 4weeks orally. The EG/PTX treated (group 3) received drinking water containing 0.75% EG for 4weeks orally and PTX. Urine and blood were collected to determine some parameters. The kidneys were also removed for histological examination. Serum and urinary parameters were significantly improved in the EG/PTX treated. In the EG/PTX-treated group, the MDA, TOS and MPO activity reduced and the TAS, SOD, CAT and GSH-Px activities were increased markedly compared with the group 2. In urine of the group 2 rats, a large number of CaOx crystals were displayed and most tubules that contained crystals were dilated and showed degeneration, necrosis, and desquamation of the lining epithelium. Only few CaOx crystals were r in EG/PTX-treated animal's urine. Mild tissue damage was observed in PTX-treated rats. iNOS expression was significantly elevated in the group 2. In contrast, in the EG/PTX-treated group, eNOS expression in renal tubular epithelial cells was increased. Current study indicates that PTX may partially reduce renal tubular injury resulting from hyperoxaluria-induced oxidative and nitrosative stress.

Effects of Pentoxifylline on Nitric Oxide Levels and Histopathology of Pancreas in Diabetic Mice

Effects of Pentoxifylline on Nitric Oxide Levels and Histopathology of Pancreas in Diabetic Mice

The Modulatory Effects of Pentoxifylline in Biochemical Changes Induced By 17α-Ethinyl Estradiol in the Rat Model

Background: Ethinylestradiol (EE) has induced cholestasis and hepatotoxicity in animal studies through reducing bile acid uptake by hepatocytes and induce of oxidative stress. Pentoxifylline (PTX) is a drug that by inhibition of release or transcription of proinflammatory cytokine cause prevents oxidative stress of liver cell and reduction of damage. We aimed to evaluate the effects of pentoxifylline on liver injury induced by Ethinylestradiol in rats. Methods: Twenty-four female Wistar rats (300±20 gr) were divided into four groups, equally. Duration of treatment was 5 consecutive days for each group. The control group Simultaneously received orally and subcutaneously normal saline. PTX group Simultaneously received Pentoxifylline orally and normal saline subcutaneously, EE Group Simultaneously received EE subcutaneously and normal saline orally. In the EE+PTX group, rats Simultaneously received EE subcutaneously and PTX orally. Rats were anesthetized and blood and tissue samples were collected for measurement of hematological and biochemical parameters. Results: The EE administration increased the serum levels of ALP and MDA significantly. The EE administration also decreased albumin and GPX levels were significant. These aberrations were improved by PTX treatment in EE + PTX group. Most of hematological parameters were not significant by the EE. The plasma level of TNF- in the PTX+ES treated group showed a significant decrease in comparison to that in the ethinyl estradiol group. Conclusion: PTX has partial capacity to protect against liver changes induced by Ethinyl Estradiol.

Pentoxifylline May Restore Kanamycin-Induced Renal Damage in Rats

Background: Kidney damage can be caused by many factors, such as using certain drugs in high doses or over the longterm. The use of one such group of drugs, aminoglycosides, which act as Gram-negative antibacterial therapeutic agents,can lead to nephrotoxicity. It has been hypothesized that aminoglycoside-induced nephrotoxicity might be prevented byusing pentoxifylline, which has antioxidant and anti-inflammatory effects and improves microcirculation. The objectiveof this present research was to determine the protective effects of pentoxifylline on kanamycin-induced kidney damage.Materials, Methods &amp; Results: Thirty-two male Wistar rats were divided into four groups as follows: control, pentoxifylline,kanamycin, and kanamycin + pentoxifylline. The control group received intraperitoneal (IP) injections of 0.5 mL normalsaline solution once a day (d) (SID) for 20 d; the pentoxifylline group received IP injections of 50 mg/kg pentoxifyllinetwice a day (BID) for 20 d, the kanamycin group received subcutaneous (SC) injections of 500 mg/kg kanamycin SID for20 d, and the kanamycin + pentoxifylline group received both SC injections of 500 mg/kg kanamycin SID and IP injectionsof 50 mg/kg pentoxifylline BID for 20 d. At the end of 20 d, blood samples were taken from the heart by cardiac punctureunder general anesthesia. After euthanizing the rats by cervical dislocation under anesthesia, the kidneys were immediatelyremoved, relative kidney weights were calculated, and routine pathologic evaluations were conducted. Hemogramparameters were measured using a blood cell count apparatus and serum biochemical parameters were measured usingan autoanalyzer. Kanamycin also caused (P &lt; 0.05) tubular degeneration and tubular dilatation. Although pentoxifyllinesignificantly reduced the level of kanamycin-induced tubular degeneration (P &lt; 0.05), it did not significantly reduce tubulardilatation. Increases in relative kidney weights (P &lt; 0.05) and in interstitial mononuclear cell (MNC) infiltrates wereobserved in the kanamycin and kanamycin + pentoxifylline groups compared to those in the control and pentoxifyllinegroups. Statistically significant changes were determined in the levels of some hemogram and biochemical parameterswithin reference ranges (P &lt; 0.05).Discussion: In this study, both tubular degeneration and dilatation were observed in the kanamycin group. Pentoxifyllineinhibited (P &lt; 0.05) kanamycin-induced tubular degeneration and appeared to also reduce tubular dilatation, although thisreduction was not significant. Tubular necrosis, epithelial edema of proximal tubules, tubular fibrosis, and perivascularinflammation might also be observed in aminoglycoside-induced nephrotoxicity. In current research, pentoxifylline preventedtubular damage induced by kanamycin, but did not inhibit infiltration by MNCs. Pentoxifylline also amelioratedamikacin- or gentamycin-induced histopathologic changes, especially those associated with tubular structures. The protectiveeffects of pentoxifylline on kanamycin-induced tubular nephrotoxicity in this research might be a result of its stimulatingthe production of prostaglandin, a vasodilator, and of its improving microcirculation. Although the anti-inflammatoryeffects of pentoxifylline have been reported, these did not inhibit kanamycin-induced infiltration by interstitial MNCs inthe present study. These results could indicate that the anti-inflammatory effects of pentoxifylline are not obvious and/orare dose dependent. Statistically significantly changes were determined in the levels of some hemogram and biochemicalparameters in reference ranges. However, these changes were within the reference ranges for rats. These results suggestedthat kanamycin-induced tubular degeneration and dilatation might be prevented by administering pentoxifylline.

Erythrocyte filterability in patients with cerebrovascular insufficiency. Effect of pentoxifylline and dipyridamole. Preliminary results

Erythrocyte filterability in patients with cerebrovascular insufficiency. Effect of pentoxifylline and dipyridamole. Preliminary results

Effects of Pentoxifylline on Soluble Klotho Concentrations and Renal Tubular Cell Expression in Diabetic Kidney Disease.

The effect of pentoxifylline on Klotho levels in patients with type 2 diabetes mellitus with chronic kidney disease (CKD) was assessed in a post hoc analysis of the Pentoxifylline for Renoprotection in Diabetic Nephropathy (PREDIAN) trial. Circulating and urinary tumor necrosis factor-α (TNF-α) and Klotho were measured before and after 1 year of pentoxifylline. The effect on Klotho expression was assessed in cultured renal tubular cells. Pentoxifylline administration resulted in decreased serum and urinary TNF-α, whereas serum and urinary Klotho increased significantly. Changes in urinary Klotho, urinary TNF-α, and phosphorus were associated with changes in serum Klotho; changes in estimated glomerular filtration rate, urinary TNF-α, and albuminuria were related to urinary Klotho variation. In renal tubular cells, pentoxifylline prevented the decrease in Klotho expression induced by inflammatory cytokines or albumin. Pentoxifylline increased Klotho levels in patients with diabetes with stage 3-4 CKD and prevented reduced Klotho expression in vitro. This beneficial effect may be related to anti-inflammatory and antialbuminuric activity.

Effects of pentoxifylline on the histological and ultra-structural features of vitrified mouse ovarian tissue: An experimental study

Vitrification is a process that can be used to preserve gonads in the healthy and natural status. Oxidative stress is one of the disadvantages of vitrification. Pentoxifylline (PTX) is an antioxidant that can reduce reactive oxidative stress effects. We aimed to investigate the effects of PTX on histological and ultra-structural features of vitrified and non-vitrified mouse ovarian tissue. Twenty-five adult female Balb-C mice were randomly and equally divided into control group: the ovaries did not receive any treatment; experimental 1 and 2: the vitrified ovaries were incubated in phosphate buffer solution and bovine serum albumin without and with PTX, respectively, for 30 min; sham 1 and 2: the non-vitrified ovaries were incubated in phosphate buffer solution and bovine serum albumin and were incubated without and with PTX, respectively for 30 min. The right and left ovaries in all of the groups were evaluated using light and transmission electron microscopy, respectively. The histological and ultra-structural features of vitrified ovaries were seriously damaged. There was non-uniformed germinal epithelium and tunica albuginea, degenerated granulosa cells and stromal cells, puffy basement membrane and irregular thickness of zona pellucida, as well as a pyknotic nucleus and bubbly and segmented ooplasmic in the follicles. Also, ovarian tissues were damaged by the PTX in the non-vitrified ovaries. Vitrification can damage the histological and ultra-structural features of the ovary in mouse models. PTX as an antioxidant, with concentration of 1.8 mM could not prevent and restore these damages and had no adequate effects on the vitrified ovarian tissues.

Abstract P-165: PENTOXIFYLLINE THERAPY IN NOSOCOMIAL SEPSIS OF PRETERM INFANTS

Aims & Objectives: Nosocomial sepsis occurring 72–96 hours after hospitalization is the most common among hospitalized acquired infections. Mortality and morbidity of sepsis is still high despite appropriate treatment. Therefore supportive therapies were tried. Low quality evidence shows that pentoxifylline in combination with antibiotics decreases death and duration of hospital stay in newborn sepsis. Our aim was to investigate the effect of pentoxifylline as an adjunct to antibiotics on neonatal nosocomial sepsis in premature infants hospitalized in NICU. Methods Eighty hospitalized premature neonates diagnosed as nosocomial sepsis were enrolled in this study. Forty of them had pentoxifylline adjuvant to antibiotics while the other 40 did not and formed the control group. We matched cases with controls for gestational age, birth weight, Apgar scores in 1st and 5th minutes, delivery type, gender, surfactant treatment, ventilatory treatment and early onset sepsis. Results There was no statistical difference between groups according to gestational week, gender, birth weight, mortality, neutrophiles count or procalcitonin level at the time of diagnosis. Also there was not any statistical difference according to duration of hospitalization BPD or NEC between groups. Conclusions Pentoxifylline has no significant impact on mortality and morbidity of preterm nosocomial sepsis.

Targeting Keap-1/Nrf-2 pathway and cytoglobin as a potential protective mechanism of diosmin and pentoxifylline against cholestatic liver cirrhosis

AimThe effects of diosmin (DS), pentoxifylline (PTX) and their combination on inflammatory response, oxidant/antioxidant balance, cytoglobin and cirrhotic reaction during bile duct ligation (BDL) were investigated and explored. Main methodsFifty adult male Wistar albino rats were randomly allocated to five groups as following, sham: received vehicle only, BDL: subjected to common BDL without treatment, BDL plus DS: received 100 mg/kg/day orally, BDL plus PTX: received 50 mg/kg/day orally, BDL plus DS plus PTX: received DS and PTX in the same manner. The test period lasted 28 days, liver tissues and blood samples were collected to investigate biochemical markers (liver function biomarkers, oxidative stress markers, and antifibrotic markers), mRNA expression of Nrf-2, Keap-1, NF-κB-p65 and p38-MAPK by real-time PCR, protein expression of cytoglobin and NF-κB-p65 by western blot and iNOS and eNOS by immunohistochemistry. Histopathological study was performed to confirm our results. Key findingsChronic BDL induced a significant alteration in liver functions, oxidative stress and fibrotic markers. Furthermore, unfavorable effects on gene and protein expression were observed after BDL. Histopathological findings of this group showed parallel effects. DS, PTX and their combination treatment significantly ameliorated the disturbance that occurred due to BDL. Similar findings were observed in liver histopathology. SignificanceDS and PTX could mitigate liver cirrhosis through modulation of Keap-1/Nrf-2/GSH and NF-κB-p65/p38-MAPK signaling pathways. In addition, we demonstrated that the hepatoprotective effect of DS and PTX is mediated by up-regulation of cytoglobin with inhibition of fibrotic reaction.