Preventive Effect of Pentoxifylline on Acute Radiation Damage via Antioxidant and Anti-inflammatory Pathways

Purpose The aim of the present study was to investigate whether pentoxifylline (PTX) treatment could protect against induced acute radiation enteritis. Method Rats received 100 mg/kg/day PTX for 7 days before irradiation and continued on treatment for 3 days after irradiation. The intestinal myeloperoxidase (MPO) activities and malondialdehyde (MDA), glutathione (GSH), prostaglandin E2, and thromboxane B2 levels were determined. Terminal ileum tissue was evaluated for morphological changes. Also, nuclear factor κ (NF-κ), tumor necrosis factor-α (TNF-α), and intercellular adhesion molecule 1 (ICAM-1) expressions were analyzed with immunohistochemisty methods. Results PTX treatment was associated with increased GSH levels and decreased MPO activity and MDA, prostaglandin E2, and thromboxane B2 levels. Histopathologic examination showed that intestinal mucosal structure was preserved in the PTX-treated group while having significant decreases in NF-κB, TNF-a, and ICAM-1 expression. Conclusions PTX appears to have a protective effect against radiation damage. This protective effect is mediated in part by decreasing both inflammatory reactions and oxidative stress.     

Effect of Pentoxifylline on the Healing of Ischemic Colorectal Anastomoses

Purpose The aim of this study was to evaluate the effect of pentoxifylline on the healing of experimental ischemic colorectal anastomoses. Methods Ninety-three Wistar rats were randomized into three groups (n = 31) and underwent resection of a colonic segment at the colorectal junction. Group A rats received standard end-to-end anastomoses. Ischemic anastomoses were performed in Groups B and C rats by coagulating mesocolon vessels 2 cm along each anastomotic end. Group C rats were treated with intraperitoneal injection of pentoxifylline. Wound complications, intra-abdominal abscesses, intraperitoneal adhesions, and anastomotic leaks and stenosis were recorded. Bursting pressure and tension were calculated. Histologic examination of the anastomosis was also performed. Results Ischemia increased wound and intra-abdominal infections, adhesion formation, and anastomotic stenosis. Anastomotic leakage was significantly higher in Group B (45.2 percent) than in Group A (9.7 percent). Bursting pressure and tension were significantly lower in Group B (118.19 mmHg and 48.43 N/m) than in Group A (191.84 mmHg and 86.82 N/m). There was evidence for decreased perianastomotic fibrosis and neutrophils presence after induced ischemia and a strong tendency to reduced neovascularization. Pentoxifylline administration ameliorated the effects of ischemia, reducing wound and intra-abdominal infections, adhesion formation, and leaks (16.1 percent). Anastomotic strength increased (bursting pressure and tension of 205.55 mmHg and 87.68 N/m, respectively). Treated Group C had significantly higher neutrophils infiltration and fibrosis formation and a strong tendency to increased neovascularization compared with Group B. Conclusions Selective anastomotic devascularization induces ischemia and impairs experimental anastomotic healing, increasing leakage rate. These effects may be ameliorated by pentoxifylline administration. Supported by a grant from the “Servicio Andaluz de Salud,” Consejería de Salud, Junta de Andalucía.     

己酮可可碱对NOD小鼠1型糖尿病的影响

目的 探讨己酮可可碱（pentoxifyline,PTX)对NOD（non-obese diabetic)小鼠1型糖尿病的影响及其机制。方法 采用动物模型NOD鼠，PTX处理后检测血糖、尿糖及糖尿病发病率，HE染色观察胰岛炎，并用RT－PCR法检测胰腺干扰素γ（IFN-γ）、肿瘤坏死因子α（TNF－α）、白介素10（IL－10）mRNA的表达。结果 PTX组糖尿病发生率(30%)低于对照组（67．9％），P＜0．01；胰岛炎程度也减轻P＜0．001；胰腺IFN－γ、TNF－α mRNA的表达较对照组降低，P＜0．05；3项变化均具显著性。而IL－10 mRNA的表达则无显著改变。结论 PTX可预防NOD小鼠发生糖尿病，其机制可能与纠正Th1与Th2型细胞因子比例失衡有关。     

己酮可可碱联合阿苯达唑治疗小鼠泡球蚴病的疗效观察

目的 观察己酮可可碱（PTX）和阿苯达唑（ABZ）单独及联合用药对小鼠继发性泡球蚴病的疗效。 方法 对小鼠继发性泡球蚴病进行药物治疗，各治疗组药物用量分别为：ABZ组 50 mg/（kg·d）；PTX高剂量组360 mg/（kg·d）；PTX低剂量组180 mg/（kg·d）；联合组 ABZ 50 mg/（kg·d） + PTX 180 mg/（kg·d）；感染对照组（未治疗组）和空白对照组均给予等体积生理盐水，用小鼠灌胃针经口每天灌胃给药1次，连续治疗100 d后 （其间14只死亡），检测各小鼠泡球蚴湿重、抑囊率及小鼠血清细胞因子转化生长因子?鄄β （TGF-β）、白细胞介素?鄄2 （IL-2）和IL?鄄10；并对泡球蚴组织进行病理组织学和超微结构观察。 结果 PTX在体外能有效地杀灭原头节（高剂量组为100%）, 在体内对泡球蚴抑制作用虽较弱（高剂量组为37%），但能增强小鼠的免疫力。联合用药对泡球蚴有明显的抑制作用，抑囊率为88 %，ABZ抑囊率为58 % （P<0.05）。 结论 PTX联合ABZ治疗小鼠继发性泡球蚴病疗效明显优于ABZ。     

已酮可可碱联合阿苯达唑治疗小鼠泡球呦病的疗效观察

目的观察己酮可可碱(PTX)和阿苯达唑(ABZ)单独及联合用药对小鼠继发性泡球蚴病的疗效。方法对小鼠继发性泡球蚴病进行药物治疗,各治疗组药物用量分别为:ABZ组50mg/(kg·d);PTX高剂量组360mg/(kg·d);PTX低剂量组180mg/(kg·d);联合组ABZ50mg/(kg·d) PTX180mg/(kg·d);感染对照组(未治疗组)和空白对照组均给予等体积生理盐水,用小鼠灌胃针经口每天灌胃给药1次,连续治疗100d后(其间14只死亡),检测各小鼠泡球蚴湿重、抑囊率及小鼠血清细胞因子转化生长因子-β(TGF-β)、白细胞介素-2(IL-2)和IL-10;并对泡球蚴组织进行病理组织学和超微结构观察。结果PTX在体外能有效地杀灭原头节(高剂量组为100%),在体内对泡球蚴抑制作用虽较弱(高剂量组为37%),但能增强小鼠的免疫力。联合用药对泡球蚴有明显的抑制作用,抑囊率为88%,ABZ抑囊率为58%(P<0.05)。结论PTX联合ABZ治疗小鼠继发性泡球蚴病疗效明显优于ABZ。     

蠕虫免疫调节分子的抗炎作用与机制

新近研究发现,一些蠕虫来源的免疫调节分子可预防或治疗小鼠模型中多种自身免疫性疾病和过敏性反应。本文综述了多种蠕虫来源的免疫调节分子及其在小鼠模型中的抗炎效应和作用机制。     

Pentoxifylline in hepatopulmonary syndrome

AIM: To determine the effects of pentoxifylline (PTX) on clinical manifestations and evaluate arterial blood gas data in hepatopulmonary syndrome (HPS) in children.METHODS: In a pilot study of 10 children with chronic liver disease, who had HPS, 20 mg/kg/d PTX was administered for 3 mo. Clinical data and arterial blood gas parameters were evaluated at baseline, the end of the treatment period, and 3 mo after drug discontinuation.RESULTS: Six patients could tolerate PTX, while four patients experienced complications. Among patients who could tolerate PTX, there was a significant increase in arterial oxygen pressure (PaO₂) (P = 0.02) and oxygen saturation (SaO₂) (P = 0.04) and alveolar-arterial oxygen gradient (P = 0.02) after 3 mo of treatment. Significant decreases in PaO₂ (P = 0.02) and alveolar-arterial oxygen gradient (P = 0.02) were also seen after drug discontinuation.CONCLUSION: PTX may improve PaO₂, SaO₂ and alveolar-arterial oxygen gradient in the early stage of HPS.     

阿托伐他汀的抗炎作用及其机制的研究进展

阿托伐他汀具有强效降脂功能,目前已被广泛用于高脂血症和心血管疾病的治疗。此外,阿托伐他汀还能明显抑制白细胞介素1β(IL-1β)、白细胞介素6(IL-6)、肿瘤坏死因子α(TNF-α)等促炎因子的合成,具有显著抗炎效应。但是,阿托伐他汀抗炎效应的具体机制还未完全阐明。本文综述了Toll样受体(TLR)、炎性体、microRNA(miRNA)、小G蛋白和过氧化体增殖物激活型受体(PPAR)在阿托伐他汀抗炎效应中的作用,为深入认识阿托伐他汀的抗炎机制提供了依据。     

Pentoxifylline improves pulmonary gas exchange

Pentoxifylline is a xanthine derivative with hemorrheologic and vascular properties that may improve gas exchange in patients with chronic obstructive pulmonary disease (COPD). We tested this hypothesis in 12 patients with COPD (mean FEV1 = 40 percent predicted; mean DCO, 8.6 ml/min/mm Hg) randomly divided into a treatment and control group and six healthy volunteers. Following establishment of baseline DCO and maximum expiratory flow volume (MEFV) curve values, each subject in the treatment and healthy groups took 400 mg of pentoxifylline three times a day for 12 weeks. Weekly DCO and MEFV curves were measured before treadmill exercise in both COPD groups and before and after exercise in the healthy group. The MEFV curve parameters from the final three weeks of therapy did not differ significantly from baseline values. During this time, however, the treatment COPD group's resting DCO rose by 8.2 +/- 2.4 percent over baseline level (p less than 0.01). Treadmill walk time increased from 17.7 +/- 2.9 minutes to 23.2 +/- 2.9 minutes (p less than 0.02). This was accompanied by improved exercise oxygen saturation measured by oximetry (SoxiO2). Premedication SoxiO2 fell from 92.8 +/- 1.2 percent to 88.6 +/- 2.5 percent during exercise, and from 94.4 +/- 1.1 percent to only 91.8 +/- 1.0 percent after 12 weeks of medication (p less than 0.05). No such improvement was noted in the control COPD group. Although the healthy group's resting SoxiO2 and DCO did not change during treatment, their exercise DCO increased significantly from 36.3 +/- 3.1 ml/min/mm Hg to 41.8 +/- 3.5 ml/min/mm Hg (p less than 0.001). These data demonstrate that pentoxifylline improves gas exchange, possibly by increasing cardiac output, and/or by raising mixed venous PO2, and/or by improving blood flow to underperfused alveoli.     

Pentoxifylline in cerebrovascular dementia.

OBJECTIVE: To test the effect of pentoxifylline, a hemorheologic agent used to treat intermittent claudication, on the course of vascular dementia. DESIGN: Randomized, double-blind, placebo-controlled, parallel group trial. SETTING: Outpatient tertiary care center. PATIENTS: 64 patients meeting DSM-III criteria for multi-infarct dementia with modified Hachinski ischemic scores greater than or equal to 6, 38 of whom completed the trial. INTERVENTION: Pentoxifylline (Trental) 400 milligram tablets three times daily vs placebo for 36 weeks. MAIN OUTCOME MEASURE: Alzheimer's Disease Assessment Scale (ADAS). RESULTS: Baseline demographic values and psychometric variables were similar in the placebo and control groups; endpoint statistical analysis was used to allow the use of data from all patients in this clinically high-risk group. For the total group, the slowing of deterioration did not reach statistical significance (by 2-tailed t test), as measured by scores on the total ADAS (P = 0.058) or on the cognitive (ADAS items 1-11; P = 0.064) or non-cognitive subscales (ADAS items 12-21; P = 0.234), although it was significant on the cognitive subscales excluding memory (ADAS items 2-6, 8-10; P = 0.036). For the subgroup of 40 patients who had CT and/or MRI evidence of stroke as well as meeting the other inclusion criteria, treatment with pentoxifylline was associated with significantly slower deterioration, as measured by the total ADAS (P = 0.023) and cognitive subscores (P = 0.020) but not non-cognitive subscores (P = 0.118). For the subgroup of 37 patients who had at least one discrete clinical stroke, treatment with pentoxifylline was associated with significantly less deterioration on the total ADAS (P = 0.002) and both the cognitive (P = 0.001) and non-cognitive (P = 0.017) subscores. CONCLUSION: Treatment with pentoxifylline may slow the progression of dementia in patients who meet DSM-III criteria for "multi-infarct dementia" and who also have clinical and neuroradiological evidence of cerebrovascular disease.     

Pentoxifylline, fibrinogen and leukocytes

Pentoxifylline has been reported to induce a decrease in plasma fibrinogen level in patients with arteritis. We report here ex vivo experiments in both healthy volunteers and patients with arteritis. In patients we have confirmed the decrease in plasma fibrinogen level during pentoxifylline therapy, and shown that the decrease is correlated with the improvement of the clinical symptoms, whereas no significant modification was noted in the healthy volunteers taking pentoxifylline. Therefore it is suggested that the decrease in fibrinogen induced in patients was due to an indirect mechanism, probably related to the pentoxifylline-induced decrease in TNF synthesis.     

Therapeutic Effect of Captopril, Pentoxifylline, and Cordyceps Sinensis in Pre-Hepatic Portal Hypertensive Rats

Background/Aim:

Portal hypertension is an important and potentially fatal complication of liver disease whereby cellular and fibrotic alterations manifest to increase portal venous pressure. The aim of this study is to investigate the effect of captopril, pentoxifylline (PTX), and cordyceps sinensis in pre-hepatic portal hypertensive rats.

Settings and Design:

Wister male rats were divided at random into 3 main groups: the first group: control rats. The second group: sham-operated rats and the third group: prehepatic portal hypertensive rats (PHPHT) induced by regulated pre-hepatic portal vein ligation. After 14 days, Group 3 was subdivided into 5 subgroups. Subgroup (1): portal vein-ligated (PVL) was killed at once; Subgroup (2): received distilled water for 30 days (untreated PVL group); subgroups 3-5 were treated with captopril (60 mg/kg, orally); PTX (100 mg/kg, orally); and C. sinensis (200 mg/kg, orally), respectively, as a single daily dose for 30 days.

Patients and Methods:

Portal pressure, nitric oxide (NO), antioxidant enzymes, Liver enzymes, and creatinine levels were measured to evaluate the status of the liver state.

Results:

Portal vein ligation produced significant increments in liver enzymes, NO, creatinine and portal pressure concomitant with significant decrements in glutathione content and superoxide dismutase activity. Treatment with captopril, PTX, and C. sinensis resulted in a significant reduction in liver enzymes, NO, creatinine and portal pressure and observable increase in antioxidant enzymes.

Conclusions:

captopril, PTX, and C. sinensis have promising effect in controlling PHPHT and reducing hyperdynamic circulatory state through reduction of portal pressure and NO level.     

急性胰腺炎促炎细胞因子和抗炎细胞因子的动态变化及其作用

目的：探讨促炎细胞因子和抗炎细胞因子在急性胰腺炎（AP）发病机制中的作用,方法：应用ELISA法检测48例病人血液中促炎细胞因子（TNF（α、IL-1β、IL-6、IL-8）和抗炎细胞因子（IL－10、IL－1ra)。结果：AP病人血液中促炎细胞因子和抗炎细胞因子在早期持续显著升高（与正常对照组相比P＜0．05）,其后逐渐下降,并与临床症状变化的时相一致。结论：促炎细胞因子和抗炎细胞因子在急性胰腺炎的发生发展过程中可能均具有重要作用。     

Pentoxifylline in the treatment of distal diabetic neuropathy

Painful diabetic distal sensory neuropathy is a disabling and common complication of diabetes mellitus. There is evidence that microvascular changes resulting in ischemia to the vasa nervorum may contribute to this problem. Pentoxifylline has been shown to improve circulation through partially occluded peripheral vessels and has been postulated to be of potential benefit. Forty adult type II diabetics were enrolled in a double-blind, placebo-controlled study utilizing pentoxifylline for six months. Visual analog scores, nerve conduction studies, and physical examinations were used to evaluate response to treatment. At the end of the six-month trial, there was no significant difference in the patients' pain between the pentoxifylline- and placebo-treated groups. The authors conclude that pentoxifylline is not useful in the treatment of painful distal diabetic neuropathy.