Pentoxifylline, oxidation

Treatment of acute respiratory distress syndrome (ARDS) or acute lung injury may be defined as a condition involving impaired oxygenation. The nonpharmacologic therapies include mechanical ventilation. The pharmacologic therapies include the use of exogenous surfactant, corticosteroids, acetylcysteine (antioxidant), ketoconazole, nitric oxide, eicosanoids and their inhibitors, sodium nitroprus-side (vasodilator), pentoxifylline, antiendotoxin, and anticytokine therapy and antibiotics. 

The diperiodatocuprate(lll) (DPC) oxidation of pentoxifylline (PTX) (14) catalysed by Ru(III) in alkaline medium proceeds via a Ru(lll)-PTX complex, which reacts with DPC and decomposes to a free radical in the rate-determining step followed by a fast step to give the products. ... 

From oxidant-stimulated (2xl0" M hypoxan-thine/4.5 mil xanthine oxidase for 15 min) human umbilical vein endothelial cells cultured in vitro, Franzini etal. (1995) concluded that cAMP is probably involved in the adherence of polymorphonuclear neutrophils. Preincubation with pentoxifylline inhibited adherence in a concentration-dependent manner. Isobutylmethylxanthine and isopren-aline, which increase intracellular cAMP content, were also inhibitory. 

After stimulation with lipopolysaccharide, pentoxifylline potentiated NO production and the expression of inducible nitric oxide synthase (iNOS) in primary porcine liver cell cultures (Hoebe et al. 2001). The increased expression of iNOS and concurrent production of NO was also observed when liver cell cultures were incubated with dibutyryl cyclic adenosine monophosphate. 

McCarty MF (1998) Nitric oxide deficiency, leukocyte activation, and resultant ischemia are crucial to the pathogenesis of diabetic retinopathy/neuropathy-preventive potential of antioxidants, essential fatty acids, chromium, ginkgolides, and pentoxifylline. Med Hypotheses 50(5) 435 9... 

A number of attempts to alter the course of ALI/ARDS pharmacologically have not been proven to be successful. These include the use of exogenous surfactant, glucocorticoids, antioxidant (n-acetylcysteine), prostaglandin and leukotriene synthesis inhibitors (hetoconazole, ibuprofen), prostaglandin El, inhaled nitric oxide, and pentoxifylline (159,160). Trials with antibodies aimed at blocking inflammation provoked by endotoxin, TNF-a, and IL-1 have also not been proven to be successful... 

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