Pentoxifylline

Freitas, J. P.; Filipe, Paulo

doi:10.1007/bf02790131

Cited by 53 publications

(13 citation statements)

References 6 publications

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“…In fact, both pentoxifylline (I) and lisofylline (II) are known for their antiinflammatory properties (5,6). It is also known that I inhibits hydroxyl radical-mediated degradation of deoxyribose (7).…”

Section: Resultsmentioning

confidence: 98%

“…Both pentoxifylline (I) and lisofylline (II) are known to possess anti-inflammatory properties (5) which are probably related to their ability to suppress oxygen radical production or scavenge reactive oxygen species (6). Ability of I to scavenge hydroxyl radicals has been demonstrated earlier (7). Although substituted xanthines such as I and II are used as drugs, the corresponding 8-oxo derivatives have never been prepared and tested for their antioxidative potential and ability to scavenge reactive oxygen species.…”

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confidence: 97%

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Antioxidant and Radical Scavenging Properties of 8-Oxo Derivatives of Xanthine Drugs Pentoxifylline and Lisofylline

Bhat

Madyastha

2001

Biochemical and Biophysical Research Communications

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The antioxidant and radical scavenging properties of 8-oxo derivatives of pentoxifylline, lisofylline, enprofylline (3-propyl xanthine), and 1,7-dimethyl enprofylline were studied in vitro. The results show that 8-oxopentoxifylline and 8-oxolisofylline are significantly better hydroxyl and peroxyl radical scavengers and more potent inhibitors of t-butylhydroperoxide-induced lipid peroxidation in human erythrocyte membranes than the parent drugs. The hydroxyl radical scavenging property of 8-oxoenprofylline and its analogue 1,7-dimethyl-8-oxoenprofylline is marginally better than their corresponding xanthines. Interestingly, 1,7-dimethyl-8-oxoenprofylline is an effective inhibitor of lipid peroxidation whereas enprofylline, 1,7-dimethylenprofylline, and 8-oxoenprofylline exhibit significantly less activity. All the 8-oxo derivatives tested are better hydroxyl radical scavengers than uric acid, a natural antioxidant and a free radical scavenger in humans. The rate constant for the reaction between 8-oxopentoxifylline and hydroxyl radical is 1.6-4.2 x 10(10) M(-1) s(-1) which is comparable to that of dimethyl sulfoxide (1.4-1.6 x 10(10) M(-1) s(-1)) and better than that of mannitol (1.9-2.5 x 10(9) M(-1) s(-1)), the known hydroxyl radical scavengers. Both 8-oxo pentoxifylline (IC(50), 1.8 +/- 0.08 microM) and 8-oxolisofylline (IC(50), 2.2 +/- 0.13 microM) are as efficient peroxyl radical scavengers as uric acid (IC(50), 1.9 +/- 0.05 microM). The results presented clearly indicate that the anti-inflammatory property of pentoxifylline and lisofylline is exerted more through their 8-oxo derivatives than through the parent drugs.

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Section: Resultsmentioning

confidence: 98%

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confidence: 97%

Antioxidant and Radical Scavenging Properties of 8-Oxo Derivatives of Xanthine Drugs Pentoxifylline and Lisofylline

Bhat

Madyastha

2001

Biochemical and Biophysical Research Communications

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“…The death pattern is apoptotic in appearance with cell rounding, chromatin condensation, formation of cytoplasmic vesicles, and blebbing, accompanied by characteristic DNA laddering. Inhibition of HIV protease-mediated apoptosis is accomplished by addition of the HIV protease inhibitor DMP323 (14), or by treating the cells with interleukin 10 (IL-10), stem cell factor, or pentoxifylline, a cytoprotectant that has metal chelating and anti-NFKB properties (15,16). Similar treatments also suppress replication of HIV (16,17).…”

Section: Resultsmentioning

confidence: 99%

Apoptosis mediated by HIV protease is preceded by cleavage of Bcl-2.

Strack

Frey²,

Rizzo³

et al. 1996

Proc. Natl. Acad. Sci. U.S.A.

187

138

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Expression of the human immunodeficiency virus type 1 (HIV) protease in cultured cells leads to apoptosis, preceded by cleavage of bcl-2, a key negative regulator of cell death. In contrast, a high level of bcl-2 protects cells in vitro and in vivo from the viral protease and prevents cell death following HIV infection of human lymphocytes, while reducing the yields of viral structural proteins, infectivity, and tumor necrosis factor a. We present a model for HIV replication in which the viral protease depletes the infected cells of bcl-2, leading to oxidative stress-dependent activation of NFKB, a cellular factor required for HIV transcription, and ultimately to cell death. Purified bcl-2 is cleaved by HIV protease between phenylalanine 112 and alanine 113. The results suggest a new option for HIV gene therapy; bcl-2 muteins that have noncleavable alterations surrounding the HIV protease cleavage site.

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“…Pentoxifylline was used with excellent responses in the treatment of oral and genital ulcers in some cases of Adamantiades-Behçet’s disease [33]. This xanthine derivative is known for its OH · -radical-scavenging properties [34], its ability to reduce superoxide [35]and TNF-α production [36]by competent cells. Improvement of clinical symptoms was also observed after intramuscular administration of free Cu-Zn SOD in 7 patients [37]and of liposome-encapsulated SOD in a limited series of patients with predominant intestinal disease [38].…”

Section: Discussionmentioning

confidence: 99%

Oxidative Stress in Adamantiades-Behçet’s Disease

et al. 1998

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Background: Adamantiades-Behçet’s disease is a chronic systemic disorder associating oral and genital ulcerative lesions with ocular and cutaneous manifestations. Previous publications report increased superoxide production by neutrophils and macrophages, increases in cytokines and malondialdehyde (MDA), as well as low levels of enzymatic antioxidant defenses. Aim: We looked for another marker of oxidative stress in Adamantiades-Behçet’s disease: the presence of clastogenic factors (CF) in patients’ plasma. In addition, we determined plasma endproducts of lipid peroxidation (MDA). Patients and Methods: We studied 20 patients and 20 controls. The clastogenic activity was evaluated by means of cytogenetic methods. This test (CF test) detects circulating prooxidants, due to their clastogenic effects after exposure of lymphocyte cultures of healthy persons to plasma ultrafiltrates from patients. The clastogenic prooxidants are lipid peroxidation products and cytokines, in particular TNF-α. Lipid peroxidation was evaluated by the Yagi method. Results: The CF test was positive in 18 out of 20 patients, while it was negative in all 20 control persons. The mean increase in chromosomal breaks was 10.6 ± 3.8 in cultures exposed to patients’ plasma and 1.3 ± 2.4 for cultures receiving control plasma (p <0.001). The clastogenic effect of patients’ plasma ultrafiltrates was significantly inhibited by superoxide dismutase (EC 1.15.1.1), suggesting an important role of the superoxide radical in the clastogenic pathway. Thiobarbituric-acid-reactive substances (expressed as nanomoles MDA per milliliter) were also significantly increased in these patients: 10.6 ± 3.2 for patients and 6.6 ± 1.4 for controls (p <0.001). Conclusion: The presence of CF in the plasma of patients, indicating the presence of circulating prooxidants with chromosome-damaging effects, confirms an oxidative stress in Adamantiades-Behçet’s disease. The anticlastogenic effect of superoxide dismutase in vitro suggests the implication of the superoxide radical. MDA levels were also significantly increased in patients.

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Pentoxifylline

Cited by 53 publications

References 6 publications

Antioxidant and Radical Scavenging Properties of 8-Oxo Derivatives of Xanthine Drugs Pentoxifylline and Lisofylline

Antioxidant and Radical Scavenging Properties of 8-Oxo Derivatives of Xanthine Drugs Pentoxifylline and Lisofylline

Apoptosis mediated by HIV protease is preceded by cleavage of Bcl-2.

Oxidative Stress in Adamantiades-Behçet’s Disease

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