Effects Of Pentoxifylline Administration Research Articles

The Effects of Pentoxifylline Administration on TGF-β1 Expression in Rats with Radiation-Induced Muscle Fibrosis

The Effects of Pentoxifylline Administration on TGF-β1 Expression in Rats with Radiation-Induced Muscle Fibrosis

Effect of pentoxifylline administration on an experimental rat model of intraperitoneal adhesion

Aim: Intraabdominal adhesions are the pathological structures that form between the peritoneal surfaces throughout the healing of the peritoneal surface defects with scar formation. Adhesions are a significant problem because they affect the quality of life, lead to morbidity and mortality, and increase health expenses. We have investigated the effectiveness of pentoxifylline (PTX), which is a methyl xanthine derivative, on the development of experimentally generated intraperitoneal adhesions in rats.Materials and Methods: In our study, 30 Wistar Albino rats, each weighing an average of 200-250 grams, were used. In this study, 3 groups of 10 rats were formed. As the adhesion model, cecotomy method was preferred and applied. Groups were classified as; the sham group, control group and PTX group. In the Sham group, merely laparotomy was applied, the control group was intraperitoneal 5 cc isotonic after the cecotomy, and the PTX group was intraperitoneal 100 mg / kg after the cecotomy. Rats were sacrificed on the 15 th day. Macroscopic, microscopic adhesion and adhesion tissues were evaluated with regard to hydroxyproline levels.Results: In the comparison of the groups from the macroscopic point of view, there was a noteworthy difference in adhesion between the sham group and the PTX group (p = 0.027) and between the control group and the PTX group (p = 0.001).Conclusion: In this study, it was observed that PTX can reduce intraabdominal adhesion and increase the level of hydroxyproline after surgery.

Pentoxifylline alleviated cardiac injury via modulating the cardiac expression of lncRNA-00654-miR-133a-SOX5 mRNA in the rat model of ischemia-reperfusion

Pentoxifylline (PTX) protects from many cardiovascular complications. It plays a critical role in stem cell proliferation and differentiation. Here, the effect of PTX administration on cardiac ischemia and dysfunction was explored. PTX in 3 doses (20, 30, and 40 mg/kg), was administered in vivo 5 min before a 45 min occlusion of the left anterior descending artery, followed by a 120 min reperfusion in male Wistar rats. The left ventricular end-diastolic pressure and dP/dtmax were assessed. Blood and cardiac tissue samples were collected for measuring the levels of cardiac enzymes and the expression of lncRNA-00654-miR-133a-SOX5. Samples of left ventricles were collected and processed for light microscopic, immunohistochemical staining for c-kit (a marker for cardiac progenitor cells) and transmission electron microscopic examination. PTX administration showed improvements in cardiac function tests, enzymes, and myocytes. Microscopic features showed minimal cardiac edema, hemorrhage, cellular inflammatory infiltration and fibrosis in addition to increased c-kit + cells in cardiac tissue samples. Notably, this treatment also produced a dose-dependent decrease in lncRNA-00654 with an increase in SOX5 mRNA and miRNA-133a-3p expressions. In conclusion, PTX has the potential to alleviate cardiac injury and increase the number of c-kit + cells following ischemia-reperfusion in the rat model via modulation of lncRNA-00654 and miR-133a-SOX5 mRNA expressions.

Effect of Pentoxifylline Administration on Hemoglobin Level of Hemodialysis Patients

AbstractBackground: Anemia is a common complication of end-stage renal disease despite sufficient iron stores. That is mainly due to the effect of chronic inflammation.Aim of Study: Our study investigated the effect of using a know drug used in intermittent claudication (named pen-toxifylline) as an adjuvant to ESA to improve anemia of hemodialysis patients.Patients and Method: Fifty hemodialysis anemic patients were included. They were assigned to two groups of equal numbers. Oral Pentoxifylline 400mg once daily was added to the treatment group which was compared to the control group over a six months period regarding hemoglobin, hematocrit, serum albumin and CRP.Results: We found no significant difference in hemoglobin or hematocrit between the two groups at the end of the study. However serum albumin was significantly higher in the treatment group (4.2±0.3) than the control group (3.8±0.4) pConclusion: Pentoxifylline had a significant effect in improving the chronic inflammatory state but its use in improving anemia of hemodialysis patients still needs further research.

The effects of pentoxifylline adminstration on fracture healing in a postmenopausal osteoporotic rat model

Previous studies report positive effects of pentoxifylline (PTX) alone or in combination with other drugs on some pathologic bone diseases as well as an ability to accelerate osteogensis and fracture healing in both animal models and human patients. The aim of this present study was to evaluate the effects of PTX administration on Hounsfield unit and bone strength at catabolic response (bone resorbing) of a fracture in an experimental rat model of ovariectomy induced osteoporosis (OVX-D). Thirty adult female rats were divided into groups as follows: 1 (OVX, control, no treatment); 2 (OVX, sham: daily distilled water); 3 (OVX, daily alendronate: 3 mg/kg); 4 (OVX, twice daily 100 mg/kg PTX) and 5 (OVX, PTX+alenderonate). OVX was induced by bilateral ovariectomy in all rats. A complete standardized osteotomy of the right femur was made after 3.5 months. PTX and alendronate treatments were performed for eight weeks. Then, rats were euthanized and had its right femur subjected to computerized tomography scanning for measuring Hounsfield unit; eventually, the samples were sent for a three point bending test for evaluation of the bone strength. Administration of PTX with 200 mg/kg and alendronate alone and in combination showed no significant alteration in Hounsfield unit and biomechanical properties of repairing callus of the complete osteotomy compared with the control group. Results showed increased bending stiffness and stress high load mean values of repairing complete osteotomy in PTX-treated rats compared to the control OVX-D.

Effect of Pentoxifylline Administration on an Experimental Rat Model of Femur Fracture Healing With Intramedullary Fixation.

Background:Globally, musculoskeletal injuries comprise a major public health problem that contributes to a large burden of disability and suffering. Pentoxifylline (PTX) has been originally used as a hemorheologic drug to treat intermittent claudication. Previous test tube and in vivo studies reported the beneficial effects of PTX on bony tissue.Objectives:This study aims to evaluate the effects of different dosages of PTX on biomechanical properties that occur during the late phase of the fracture healing process following a complete femoral osteotomy in a rat model. We applied intramedullary pin fixation as the treatment of choice.Materials and Methods:This experimental study was conducted at the Shahid Beheshti University of Medical Sciences, Tehran, Iran. We used the simple random technique to divide 35 female rats into five groups. Group 1 received intraperitoneal (i.p.) PTX (50 mg/kg, once daily) injections, starting 15 days before surgery, and group 2, group 3, and group 4 received 50 mg/kg, 100 mg/kg, and 200 mg/kg i.p. PTX injections, respectively, once daily after surgery. All animals across groups received treatment for six weeks (until sacrificed). Complete surgical transverse osteotomy was performed in the right femur of all rats. At six weeks after surgery, the femurs were subjected to a three-point bending test.Results:Daily administration of 50 mg/kg PTX (groups 1 and 2) decreased the high stress load in repairing osteotomized femurs when compared with the control group. The highest dose of PTX (200 mg/kg) significantly increased the high stress load when compared with the control group (P = 0.030), group 1 (P = 0.023), group 2 (P = 0.008), and group 3 (P = 0.010), per the LSD findings.Conclusions:Treatment with 200 mg/kg PTX accelerated fracture healing when compared with the control group.

Effects of pentoxifylline administration on histomorphological parameters of streptozotocin-induced diabetic rat testes.

The effect of pentoxifylline (PTX) administration on histomorphological parameters of streptozotocin (STZ)-induced type 1 diabetes mellitus (DM) in male rat testes were evaluated. We randomly divided 40 male rats into the following four groups: group 1: control or normal glycemic (NG) rats; group 2 or NG rats that received only normal saline (NS), (NG+NS); group 3 or diabetic rats which were not treated by PTX (DM+vehicle solution (NS)); and group 4 which comprised diabetic rats treated with 50 mg/kg of PTX (DM+PTX). Type 1 DM was induced by intraperitoneal injection of STZ (55 mg/kg). Rats were held for 30 days after which the experimental group received PTX twice daily (25 mg/kg) or NS. After 14 days of treatment by PTX or NS, the left testes from all rats were extracted and prpared for histological study. Apoptotic cells, blood vessel density, and spermatogenesis were evaluated. Data were analyzed by ANOVA test. PTX-treated-diabetic rats showed a significant decrease in number of apoptotic cells and decrease in blood vessel density compared to the DM+NS rats. A significant increase in spermatogenesis was observed in the PTX-treated diabetic group, compared to the DM+NS groups. It was concluded that PTX administration to STZ-induced type 1 DM rats affected apoptotic cell number positively. Moreover, blood vessel density significantly decreased and improvements were observed in spermatogenesis.

Effects of pentoxifylline administration on urinary N-acetyl-β-glucosaminidase excretion in type 2 diabetic patients: a short-term, prospective, randomized study

Background:Tubulointerstitial injury is a major feature of diabetic nephropathy and an important predictor of renal dysfunction. In 45 patients with type 2 diabetes mellitus (DM), we prospectively analyzed urinary excretion of N-acetyl-β-glucosaminidase (NAG), a marker of tubular renal damage; the potential relationship with urinary protein excretion; and effects of pentoxifylline (PTF) administration. Methods:Forty-five patients with type 2 DM initially were compared with 15 healthy controls matched for age and sex. After randomization, PTF (1,200 mg/d) was administered for 4 months to 30 patients and results were compared with data from a control group (n = 15). Results:Proteinuria and urinary NAG excretion were significantly greater in patients with DM with respect to healthy controls. Before PTF administration, baseline parameters were similar in both groups of patients with DM. At the end of the study, urinary protein excretion and NAG-creatinine ratios decreased in the active group from 920 ± 522 mg/d and 14.3 ± 16.9 U/g to 803 ± 523 mg/d (P < 0.001) and 10.5 ± 9.3 U/g (P < 0.05), respectively. Conversely, proteinuria and urinary NAG excretion did not change in the control group. Regression analysis showed that urinary NAG excretion was significantly associated with duration of DM (r = 0.61; P < 0.001) and proteinuria (r = 0.51; P < 0.001). Conclusion:Urinary NAG excretion is elevated in patients with type 2 DM compared with healthy individuals and increases as nephropathy progresses. PTF administration is effective in reducing proteinuria and urinary NAG excretion in these patients. These findings suggest that PTF may have beneficial effects on tubulointerstitial damage in diabetic kidney disease.

Improved response of colon cancer xenografts to radioimmunotherapy with pentoxifylline treatment.

A methylxanthine, pentoxifylline (PTX), has the potential to improve tumour microcirculation and oxygenation in vivo. We aimed to determine whether this agent would enhance the response of tumours to experimental radioimmunotherapy (RIT). Balb/c nu/nu mice with xenografts of LS180 human colon cancer were treated with 4.63 MBq of 131I-A7 anti-colorectal monoclonal antibody. A dose of 50 mg/kg of PTX was administered i.p. immediately after the 131I-A7 injection and daily thereafter for 7 days. The effect of PTX administration on 131I-A7 targeting in tumours was assessed with biodistribution and radioluminography on day 2. Intratumoural pO2 was measured with microelectrodes. The administration of PTX alone did not suppress tumour growth, but the efficacy of RIT with 131I-A7 was significantly improved by PTX: tumour volumes on day 15, relative to the initial volume, were 16.8+/-3.60 in the nontreated controls, 13.9+/-2.17 with PTX, 3.43+/-0.44 with RIT, and 1.86+/-0.59 with RIT+PTX (P<0.05). PTX administration did not alter the biodistribution or intratumoural distribution of 131I-A7. However, intratumoural pO2 was significantly improved by PTX administration: 16.9+/-9.75 mmHg in control tumours versus 25.6+/-11.3 mmHg in PTX-treated tumours (P<0.01). These results indicate that PTX-induced radiosensitisation of tumour cells due to better oxygenation is responsible for the better RIT outcomes, because the net radiation absorbed dose to the tumours did not appear to be changed.

Hepatosplanchnic and peripheral tissue oxygenation during treatment of hemorrhagic shock: the effects of pentoxifylline administration.

To evaluate the effects of pentoxifylline (PF) administration on liver, gut, and peripheral oxygenation during crystalloid resuscitation of hemorrhagic shock. Hypoperfusion of the hepatosplanchnic vascular bed and hypoxia of vital organs may be prolonged despite adequate therapy of hemorrhagic shock. Vasoconstriction, leukostasis, platelet aggregation, and red blood cell plugging could be the underlying causes. PF has been shown to counteract these effects, but its effects in a large animal shock model have been less studied. Thirteen anesthetized piglets (mean weight 19.6 kg) were bled steadily to a mean arterial pressure (MAP) of 40 to 50 mmHg and a 70% reduction in cardiac output during 1 hour. These levels were maintained for an additional hour. The animals were resuscitated with acetated Ringer's solution according to MAP and cardiac output values and followed for 80 minutes (total 3 hours and 20 minutes). Seven piglets were given PF boluses (12.5 mg/kg) and infusion (0.2 mg/kg x min), and the rest (n = 6) served as controls. Hemodynamic and systemic oxygen transport variables were recorded. Liver parenchymal and peripheral tissue (subcutaneous, transcutaneous, conjunctival) oxygen tensions (PO2) were measured continuously with polarographic electrodes. Jejunal intramucosal pH (pHi) was calculated every hour by the luminal PCO2, obtained with a balloon tonometer, and arterial bicarbonate concentration. Cardiac output decreased by a mean of 76% during shock and was restored during resuscitation in both groups. MAP decreased from 110 to 40 mmHg but remained at 70 to 80 mmHg during resuscitation in both groups despite remarkable volume load (2.6 ml/min per kg). Liver parenchymal PO2 decreased from 29+/-1 to 15+/-1 mmHg during shock and increased to 36+/-2 mmHg in the PF group, whereas in control group it remained at 26 mmHg. The difference between groups was significant, but at the end of follow-up the liver PO2 decreased to 21 mmHg in both groups. Gut pHi, peripheral tissue oxygen tensions, and the plasma adrenaline and noradrenaline concentrations did not differ between the groups. Pentoxifylline improved specifically, although only transiently, liver tissue oxygenation. Perhaps the microvascular abnormalities after resuscitation of hemorrhagic shock are more prominent in the hepatic vascular bed, rendering PF specifically effective in that area. The lack of any effect of PF on gut and peripheral tissue oxygenation may have resulted from the persistent vasoconstriction and inadequate restoration of blood volume with crystalloid solution.