Gamma and Pulse Radiolysis Study of Pentoxifylline, a Methylxanthine

Pasquier, Claude; Franzini, E.; Abedinzadeh, Z.; Kaouadji, Mourad; Hakim, Jacques

doi:10.1080/09553009114552291

Cited by 19 publications

(8 citation statements)

References 23 publications

(34 reference statements)

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“…Earlier studies have indicated that xanthine drug, pentoxifylline (I) reduces oxygen radical production and protects against tissue damage in vivo by the action of its metabolites (25). 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: 99%

“…Pentoxifylline (I) is widely used in the treatment of cerebrovascular and peripheral vascular diseases (1)(2)(3). 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).…”

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confidence: 99%

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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: 99%

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confidence: 99%

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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“…Pentoxifylline OH . scavenger activity has been described [46,47]. However, pentoxifylline is water‐soluble and may therefore be effective against OH .…”

Section: Discussionmentioning

confidence: 99%

Oxidative modification of high‐density lipoprotein 3 induced by human polymorphonuclear neutrophils

Cogny

Paul

Surbled

et al. 1999

European Journal of Biochemistry

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The function of high-density lipoproteins (HDLs) in reverse cholesterol transport is impaired if HDLs are subjected to oxidative stress. Polymorphonuclear neutrophils (PMNs), which have been detected in the earliest stages of atherosclerotic lesions, are one of the most likely sources of the reactive oxygen species that cause such stress.In this study, we investigated the effect of a PMN oxidative burst on HDL3. We also studied the impact on these events of pentoxifylline, a drug that regulates granulocyte function.HDL3 (370 nmol´mL 21 cholesterol-HDL) was incubated with PMNs (2 £ 10 6´m L 21 ) in NaCl/P i in the presence or absence of an iron chelate complex (10 mm Fe-nitrilotriacetic acid) at 37 8C for 60 min or 24 h. Phorbol myristate acetate (PMA) or formyl-methionylleucyphenylalanine (fMetLeuPhe) was used to stimulate PMNs. In iron-free NaCl/P i medium, PMA-stimulated PMNs had a 40% lower HDL3 a-tocopherol content, whatever the incubation time. In NaCl/P i medium containing iron, there was 80% less HDL3 a-tocopherol at 60 min, and HDL3 atocopherol had almost disappeared after 24 h. In this latter condition, the amount of thiobarbituric acid-reactive substances was significantly higher than the respective control HDL3 (P , 0.05) and oxidation of HDL3 by PMAstimulated PMNs was associated with cross-linking of apoprotein AI, which was detected by SDS/PAGE. Similar results were obtained with fMetLeuPhe-stimulated PMN except that HDL3 a-tocopherol was consumed much more slowly during the first 60 min. Pretreatment of PMNs with various concentrations of pentoxifylline (0.001±20 mm) led to the concentration-dependent inhibition of oxidative modification of HDL3 induced by stimulated PMNs. The addition of 20 mm pentoxifylline in the most extreme oxidative stress conditions resulted in 70% of HDL3 atocopherol being maintained, with no formation of thiobarbituric acid-reactive substances and a lower level of apoprotein AI cross-linking.Thus HDL3 is susceptible to oxidative modifications induced by stimulated PMNs, in the presence of an exogenous source of iron. Pentoxifylline inhibited the oxidative modification of HDL3 by PMNs.

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“…PTX induces structural defects in the neutrophil cytoskeleton [15] and we have reported the inhibitory effect of antimicrotubular agents on monocyte TF production [16]. Recently, PTX was reported to be a scavenger of hydroxyl radicals and to have protective effects against hydroxyl radical-induced damage [17]. Since the effect of such radicals has been suggested to be involved in the LPS-induced transactivation of nuclear factor-kB [18], this mechanism might also contribute to TF mRNA down-regulation by PTX.…”

Section: Relative Fluorescence Intensitymentioning

confidence: 99%

Pentoxifylline inhibits the expression of tissue factor mRNA in endotoxin‐activated human monocytes

Ollivier

Ternisien

et al. 1993

FEBS Letters

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Tissue factor (TF) is a transmembrane glycoprotein which, in association with factor VII(a), is the main activator of coagulation. In illnesses such as Gram-negative endotoxemia, circulating monocytes synthesize and express substantial TF activity, resulting in extensive disseminated intravascular coagulation. We investigated the way in which TF is suppressed by pentoxifylline (PTX), and found that PTX down-regulates immunologic TF expression and specific mRNA production in response to LPS. Since TF mRNA stability is not altered, this effect appears to take place at the transcriptional level.

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Gamma and Pulse Radiolysis Study of Pentoxifylline, a Methylxanthine

Cited by 19 publications

References 23 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

Oxidative modification of high‐density lipoprotein 3 induced by human polymorphonuclear neutrophils

Pentoxifylline inhibits the expression of tissue factor mRNA in endotoxin‐activated human monocytes

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