Effect of pentoxifylline on veno-occlusive priapism-induced corporeal tissule lipid peroxidation in a rat model

Objective: To investigate whether pentoxifylline could play a role in attenuation of the hazardous effects of ischemia/reperfusion on corporeal tissue in a rat model of veno-occlusive priapism (VOP). Materials and methods: Placebo and pentoxifylline were given to eight groups of rats prior to priapism being induced by a vacuum constrictive device for durations of 6 and 12 h, respectively. Half of the groups of rats that underwent the same duration of priapism (ischemic) were subjected to 1 h of detumescence after band removal (reperfusion). One group underwent no manipulation and no drug administration and served as a baseline determination (control). Corporeal homogenates were examined for lipid peroxidation (LP) derived malondialdehyde (MDA) accumulation via thiobarbituric acid assay. Results: MDA concentration differed significantly between VOP rats and controls (P < 0.001) but did not differ significantly between ischemic-only groups and reperfused groups (P > 0.05). In the pentoxifyllinepretreated groups, although MDA accumulation tended to be slightly lower than in the placebo groups, the difference was not statistically significant (P > 0.05) either in the 6- or 12-h duration priapic groups. Conclusions: LP, an indicator of radical oxygen metabolite (ROM) induced injury, occurs in rat corporeal tissue during and after abolishment of VOP. Single-dose pentoxifylline pretreatment failed to exert a protective effect on corporeal tissue in a rat model of VOP in terms of attenuation of LP.     

Pentoxifylline attenuates the development of hyperalgesia in a rat model of neuropathic pain

Pentoxifylline, a non-specific cytokine inhibitor, has shown to be beneficial in inflammatory pain in both experimental and clinical studies. The present study demonstrates for the first time, to our knowledge, the antihyperalgesic effect of pentoxifylline in the neuropathic pain using L5 spinal nerve transection rat model. In a preventive paradigm, pentoxifylline (12.5, 25, 50, or 100 mg/kg intraperitoneally) was administered systemically daily, beginning 1 h prior to nerve transection. Pentoxifylline (50, or 100 mg/kg i.p.) produced significant decrease in the mechanical and thermal hyperalgesia. However, pentoxifylline (100 mg/kg i.p.) did not influence the paw pressure thresholds and paw withdrawal latency in sham-operated rats. In order to understand the possible antinocicieptive effect of pentoxifylline in neuropathic pain, we examined the level of TNFα, IL-1β, IL-6 and IL-10 protein in the contralateral brain on day 7 post-transection. Pentoxifylline administration resulted in a dose-dependent reduction of the production of proinflammatory cytokines like TNFα, IL-1β and IL-6, and enhancement of IL-10. Furthermore, we investigated the activity of nuclear factor kappa B (NF-κB) in the contralateral brain on days 7 after surgery. In accordance with the change of proinflammatory cytokines, Pentoxifylline (50 or 100 mg/kg) significantly inhibited the activation of NF-κB in the brain. This research supports a growing body of literature emphasizing the importance of neuroinflammation and neuroimmune activation in the development of neuropathic pain states, and the potential preventive value of pentoxifylline in the treatment of neuropathic pain.     

Pentoxifylline and intravenous gamma globulin combination therapy for acute Kawasaki disease

We compared the efficacy of oral administration of pentoxifylline (PTX) and intravenous infusions of gamma globulin (IVGG) combination therapy with that of IVGG in reducing the frequency of coronary-artery lesions (CAL) in children with Kawasaki disease (KD), in a randomized trial. All patients with KD received acetylsalicylic acid (30 mg/kg per day), until the 30th day, after the onset of fever, followed by daily acetylsalicylic acid at a dose of 3-5 mg/kg per day there-after, and intravenous IVGG, 200 mg/kg per day, for 5 consecutive days. In addition, patients randomly assigned to PTX and IVGG combination therapy groups received oral PTX at a dosage of 10 mg/kg per day (low-dose) or 20 mg/kg per day (high-dose), in three divided doses until the 30th day. Patients with KD were all free from CAL prior to treatment. We assessed the presence of CAL by two-dimensional echocardiography which was also done prior to treatment and then twice a week after hospital admission. We detected CAL in 3 of 18 patients (16.7%) in the IVGG therapy group, as compared with 2 of 18 patients (11.1%) in the low-dose PTX and IVGG combination therapy group. There were no significant differences between the two groups. In the next study, we detected CAL in 3 of 21 patients (14.3%) in the IVGG therapy group, as compared with none of 22 patients (0%) in the high-dose PTX and IVGG combination therapy group (² = 6.4, P < 0.02). No adverse side-effects were observed in 79 patients with KD.     

Pentoxifylline reduces plasma tumour necrosis factor-alpha concentration in premature infants with sepsis

Increased plasma tumour necrosis factor (TNF) concentration correlates with mortality in sepsis. We suggested that pentoxifylline (PTXF), which is known to inhibit TNF production, may improve survival and attenuate clinical symptoms of sepsis in neonates. Plasma TNF levels were evaluated in 29 newborn infants with sepsis. Patients were randomly assigned into two groups, receiving PTXF in a dose of 5 mg/kg per hour for 6 h or placebo (saline), on 3 successive days. Both groups were subjected to the same conventional therapy. TNF was evaluated before and after PTXF or placebo administration on the 1 st and 3rd days of therapy. There was a statistically significant decrease in plasma TNF level in the PTXF group when the values before the first and after the last PTXF infusion were compared [mean: 671.5 pg/ml; SD: 438; med: 729.6 vs mean: 41.0 pg/ml; SD: 64.1; med: 11.5;P<0.000004]. In the placebo group, decrease was not significant [mean: 633.0 pg/ml SD: 488.6; med: 618.9 vs 246.9 pg/ml; SD: 243.9; med: 191.0]. A significantly higher plasma TNF level, evaluated after the last PTXF infusion, was found in the placebo group [246,9 pg/ml vs 41.0 pg/ml;P<0.001]. Only one of four infants with signs of shock in the placebo group survived, whereas all of five newborns with symptoms of shock in the PTXF group survived [P<0.04]. An increased incidence of metabolic acidosis [P<0.05], necrotizing enterocolitis [P<0.04] and renal insufficiency [P<0.05] was observed in infants in the placebo group.Conclusion PTXF inhibits production of TNF and may have therapeutic value in the treatment of premature infants with sepsis complicatea by shock.     

己酮可可碱在高机械通气诱导大白鼠肺损伤炎性反应中的作用

目的探讨己酮可可碱(pentoxifylline,PTX)在大容量机械通气诱导的大白鼠肺损伤炎性反应中的作用。方法大白鼠在接受4h大容量机械通气时,治疗组(8只)静脉给予PTX,对照组(15只)静脉给予生理盐水,比较通气前后气道灌洗液中血栓烷B2(thromboxane B2,TXB2)、肿瘤坏死因子α(tumor necrosis factor-alpha,TNF-α)、血小板活性因子(platelet activating factor,PAF)、肺组织髓过氧化物酶(myeloperoxidase,MPO)水平和肺组织湿干重量比。结果气道灌洗液中TXB2治疗组通气前为(17±4)ng/L,通气后为(13±1)ng/L,对照组通气前为(15±2)ng/L,通气后为(21±2)ng/L,两组通气后比较差异有统计学意义(P<0.01);TNF-α治疗组通气前为(39±19)ng/L,通气后为(245±76)ng/L,对照组通气前为(29±16)ng/L通气后为(620±112)ng/L,两组通气后比较差异有统计学意义(P<0.01);PAF两组通气后比较差异无统计学意义。治疗组肺组织MPO为(0.6±0.1)OD/g,对照组为(1.4±0.7)OD/g(P<0.01);治疗组肺组织湿干重量比为(6.3±0.3)g/g,对照组为(7.3±0.4)g/g(P<0.01)。结论PTX在抑制大容量机械通气诱导大白鼠肺损伤的炎性反应中有一定的积极作用。     

新生大鼠缺氧缺血性脑病模型中己酮可可碱的干预作用研究

目的观察不同时间给予己酮可可碱(pentoxifylline,PTX)对新生大鼠缺氧缺血性脑损伤(hypoxic-ischemic brain damage,HIBD)模型的影响。方法建立新生大鼠HIBD模型,120只出生7 d的wistar大鼠随机分为假手术(Sham)组、HIBD模型组和3种PTX(50 mg／kg腹腔注射)给药组,即缺血末均给药(I PTX)组、缺氧末给药(H PTX)组及缺血和缺氧末均给药(I,H PTX)组,各组均于缺血缺氧处理后72 h取出左脑,测定脑组织水含量、大脑皮层神经组织游离钙离子浓度、超氧化物歧化酶(SOD)、丙二醛(MDA)、一氧化氮合酶(NOS)及一氧化氮(NO)。结果HIBD模型组与Sham组相比,脑组织含水量、游离钙离子浓度、MDA、NOS及NO水平显著升高(均P＜0.01),SOD水平明显降低(P＜0.01)。3种PTX给药组与HIBD模型组相比,脑组织含水量、游离钙离子浓度、MDA、NOS及NO水平均显著降低(均P＜0.01),SOD水平明显升高(P＜0.01)。以上作用尤以(I,H PTX)组明显。结论 PTX对新生大鼠缺氧缺血后脑组织有保护作用,其机制可能与PTX改善能量代谢及减少局部细胞毒性物质有关。     

己酮可可碱治疗急性呼吸窘迫综合征疗效观察

目的探讨己酮可可碱联合机械通气治疗急性呼吸窘迫综合征（ARDS）的临床疗效。方法将64例ARDS患者随机分为对照组和己酮可可碱组（PTX组）各32例。对照组采用常规治疗,PTX组患者在此基础上加用己酮可可碱注射液200mg,每日2次。观察两组患者治疗效果、血气分析指标及血清中肿瘤坏死因子α（TNF-α）、白细胞介素8（IL-8）含量变化。结果治疗后3、7d两组患者动脉血氧分压（PaO2）、氧合指数（PaO2／FiO2）差异有统计学意义（P〈0．05）,PTX组血清TNF—α、IL-8及病死率均低于对照组（P〈0．05）。结论PTX联合机械通气治疗能够有效阻抑ARDS患者的炎性反应,改善患者氧合情况和预后。     

高糖及己酮可可碱对肾间质成纤维细胞作用的研究

目的：探讨糖尿病肾病肾间质病变的机理以及己酮可可碱对肾间质成纤维细胞的作用。方法：为研究高糖对肾间质成纤维细胞的作用,应用MTT比色法检测细胞的增殖,应用流式细胞仪检测细胞周期变化,并应用ELISA法检测细胞上清液中的纤维连接蛋白。同时,本研究也观察了己酮可可碱（Pentoxifylline),一种非选择性的磷酸二酯酶抑制剂对肾间质成纤维细胞的作用。结果：高糖和己酮可可碱均可抑制细胞增殖,影响细胞周期,但高糖可促进成纤维细胞分泌细胞外基质纤维连接蛋白,而己酮可可碱可减少其分泌,且可抑制高糖对成纤维细胞的作用。结论：高糖可能通过促进肾间质成纤维细胞分泌细胞外基质在糖尿病肾病的间质病变中起作用。而己酮可可碱抑制细胞增殖及细胞外基质的分泌将有利于肾间质病变的防治。     

己酮可可碱对溃结鼠NF-κB,IL-1β基因表达的影响

目的 观察PTX对UC大鼠肠黏膜组织NF-κB和IL-1β表达的影响,并探讨其机理.方法 将45只雄性Wistar大鼠随机分为对照组、模型组、治疗组,每组15只,模型组和治疗组用应用TNBS建立UC模型,3d后,治疗组给予PTX治疗,其余两组则给予等量生理盐水,持续5d.评价各组大鼠结肠组织大体及组织病理学改变,免疫组化法检测NF-кB,IL-1β蛋白在肠黏膜中的定位及表达,应用RT-PCR法检测IL-1β mRNA的表达.结果 ①大鼠结肠组织大体形态学及组织病理学评分：治疗组及对照组症状好于模型组,差异有统计学意义（P〈0.05）;②模型组NF-кB,IL-1β阳性细胞表达水平及IL-1β mRNA的表达明显增高,且明显高于治疗组和对照组（P〈0.05）,给予PTX治疗后NF-кB,IL-1β及其mRNA的表达明显降低,且与对照组无明显差异（P〉0.05）.结论 NF-кB,IL-1β与UC关系密切,PTX可能通过抑制NF-κB的活性,减少IL-1β等细胞因子的表达而起到抗炎作用.     

The effect of pentoxifylline on the flow properties of human blood

Summary

Recent investigations have revealed that erythrocytes from patients with chronic arterial occlusive disease are significantly less deformable than red blood cells from healthy subjects. The influence of pentoxifylline on red blood cell fluidity was measured by a standard filtration technique using 8 μm membrane filters. Impaired deformability of erythrocytes was significantly improved in patients suffering from peripheral vascular disorders following intravenous injection of 200?mg pentoxifylline. Studies on reduced red cell deformability induced by hyperosmolarity in vitro showed that pentoxifylline (4 and 20 μg/ml) produced a dose-dependent improvement both in blood from healthy subjects and from patients with peripheral arterial occlusive disease. The results suggest that the positive therapeutic effect of pentoxifylline in peripheral arterial occlusive disease is mediated by improving red cell fluidity in the microcirculation.