Free Radical Mediator Research Articles

Antitrichomonal action of emodin in mice

Emodin, an active component contained in the root and rhizome of Rheum palmatum L. (Polygonaceae), was found to have an inhibitory effect on the pathogenicity of Trichomonas vaginalis in mice. Emodin delayed the development of subcutaneous abscesses due to infection of this parasite. Also, it cures the intravaginal infection of trichomonads through oral administration. In cell cultures, it reduced the cytotoxic effect of this parasite towards mammalian cells. This inhibition was markedly reversed by the coexistence of free radical scavengers, indicating the possible mediation of free radicals.

Iodide as the mediator for the reductive reactions of peroxidases.

Lignin peroxidase H2 (LiPH2) from the white rot fungus Phanerochaete chrysosporium catalyzed the reduction of cytochrome c, nitro blue tetrazolium, ferric iron, molecular oxygen, and triiodide in a reaction mixture containing LiPH2, H2O2, EDTA, and iodide. Activity followed first order kinetics with respect to EDTA concentration. The reductive activity observed with LiPH2 using iodide as the mediator was comparable to that obtained using a variety of other free radical mediators such as veratryl alcohol, 1,4-dimethoxybenzene, and 1,2,3- and 1,2,4-trimethoxybenzene. EDTA-derived radicals were detected by ESR spin trapping upon incubation of LiPH2 with H2O2, iodide, and EDTA. Reduction activity was also observed using other peroxidases such as lactoperoxidase, horseradish peroxidase, and myeloperoxidase. For the reduction activity of LiPH2, it is proposed that the oxidation of EDTA is mediated by the iodide radical, and the reduction of various electron acceptors is mediated by EDTA radicals. The inhibition of reduction activity at higher concentrations of iodide might be due to the combination of iodide radicals to form I2 which forms a stable triiodide complex by reacting with excess iodide.

On the mechanism of inhibition of the veratryl alcohol oxidase activity of lignin peroxidase H2 by EDTA.

The mechanism of inhibition of the veratryl alcohol oxidase activity of lignin peroxidase H2 (LiPH2) by EDTA was investigated. It was found that EDTA was decarboxylated and that cytochrome c, nitro blue tetrazolium, ferric iron, and molecular oxygen were reduced in a reaction mixture containing LiPH2, H2O2, veratryl alcohol, and EDTA. The reductive activity observed with LiPH2 followed first order kinetics with respect to the concentration of EDTA. Stoichiometry studies showed that in the presence of sufficient EDTA, 1.7 mol of ferric iron were reduced per mole of H2O2 added to the reaction mixture. Superoxide- and EDTA-derived radicals were detected by ESR spin trapping upon incubation of LiPH2 with H2O2, veratryl alcohol, and EDTA. The Km values of veratryl alcohol and H2O2 remained the same for both the oxidative and reductive activities of LiPH2. Reductive activity was also observed with LiPH2 and EDTA using other free radical mediators in the place of veratryl alcohol, such as 1,4-dimethoxybenzene, 1,2,3- and 1,2,4-trimethoxybenzenes, and 1,2,4,5-tetramethoxybenzene. EDTA reduced the cation radical of 1,2,4,5-tetramethoxybenzene formed by LiPH2 in the presence of H2O2. Hence, it is proposed that the apparent inhibition of the veratryl alcohol oxidase activity of LiPH2 by EDTA is due to the reduction of the veratryl alcohol cation radical intermediate back to veratryl alcohol by EDTA. The reduction of cytochrome c, nitro blue tetrazolium, ferric ion, and molecular oxygen appears to be mediated by the EDTA radical formed by reduction of the veratryl alcohol cation radical.

Thiazolidine derivatives: A new source of α-aminoalkyl radicals for carbon-carbon bond formation in synthesis

α-Aminoalkyl radicals generated from N-ethoxycarbonyl- or N-methylcarbonyl-1,3-thiazolidine derivatives ( 1a, 1b, 5, 7) have been utilized in the formation of carbon-carbon bonds with tris(trimethylsilyl)silane as a free radical mediator.

Postischemic cerebral lipid peroxidation in vitro: modification by dietary vitamin E.

Using an in vitro system, we studied the effect of postischemic reoxygenation on cerebral lipid peroxidation in relation to the dietary intake of vitamin E (VE) in rats. Homogenates prepared from VE-deficient, -normal, and -supplemented brains, which were previously rendered ischemic for 30 min by decapitation, were incubated under air or nitrogen gas for 60 min. The extent of peroxidation in brain tissue was estimated by a thiobarbituric acid (TBA) test and by diene conjugation in total lipid extracts. The brain levels of alpha-tocopherol and of total and free fatty acids (FAs) were also determined. Aerobic incubation increased TBA reactants in all dietary groups; the effect was largest in the VE-deficient group, intermediate in the VE-normal group, and smallest in the VE-supplemented group. In contrast, nitrogen incubation did not alter the basal levels of TBA reactants except for a small rise associated with VE deficiency. Conjugated dienes changed in parallel with TBA reactants. alpha-Tocopherol decreased after aerobic incubation and also, to a lesser degree, after nitrogen incubation in each dietary group. Only in the reoxygenated samples of the VE-deficient group was there a significant fall in total polyunsaturated FAs. The levels of free FAs continuously increased throughout ischemia and subsequent incubation. However, the level of free polyunsaturated FAs was similar after aerobic and nitrogen incubation in each dietary group, and was not affected by VE. Thus, cerebral reoxygenation after ischemia propagates peroxidative reactions within esterified polyunsaturated FAs. The modification by VE of reoxygenation-induced lipid peroxidation suggests free radical mediation.

Neutrophil-derived, oxygen free radical-mediated cardiovascular dysfunction

Oxygen free radicals and their metabolites generated from activated neutrophils have been implicated in mediating the cardiovascular dysfunction of such diverse etiologies as myocardial ischemia and reperfusion injury, Gram negative sepsis, myocarditis and acute cardiac allograft rejection, but a direct demonstration of neutrophil derived oxygen free radical mediation of cardiovascular dysfunction has not been accomplished. In this study, we have demonstrated that activation of the canine neutrophil system, in vivo, results in the generation of oxygen free radicals that are capable of disrupting cardiovascular function producing a significant decrease in mean arterial pressure and cardiac index without any significant effect on the conduction system of the myocardium. Neutrophil depletion or pretreatment with superoxide dismutase and catalase inhibited the effects of activated neutrophils. This study provides evidence that neutrophil-derived reduced oxygen intermediates are able to induce severe cardiovascular dysfunction.

Free radical mediation of the effects of acidosis on calcium transport by cardiac sarcoplasmic reticulum in whole heart homogenates.

Generation of oxygen free radicals by xanthine acting on xanthine oxidase as a substrate significantly depressed calcium transport by sarcoplasmic reticulum in canine whole heart homogenates at 37 degrees C. At pH 7.0, this effect was completely inhibited by the addition of superoxide dismutase (SOD), a scavenger of the superoxide anion radical. At pH 6.4, SOD (5 to 20 micrograms X ml-1) was ineffective but catalase (20 micrograms X ml-1) was able to inhibit the effects of the xanthine-xanthine oxidase system. SOD + catalase (20 micrograms X ml-1) and SOD + mannitol, a scavenger of the hydroxyl free radical, inhibited the effects of the xanthine-xanthine oxidase system at pH 6.4. Preincubation at pH 6.4, in the absence of an exogenous free radical generating system, depressed calcium transport. This depression was more severe the longer the duration of incubation. However, return of the pH to 7.0 after preincubation at pH 6.4 partially restored calcium uptake velocity. The degree of reversibility was decreased the longer the period of incubation at pH 6.4. SOD reversed the effects of incubation at pH 6.4 for 5 min, but not those for incubations of 10 and 15 min. Mannitol alone was ineffective. The combinations of SOD and mannitol significantly reversed the effects of pH 6.4 up to 15 min. These results demonstrate that both exogenously generated and endogenously generated free oxygen radicals are capable of depressing calcium transport by cardiac sarcoplasmic reticulum in the whole heart homogenate in the presence of endogenous scavenging systems.(ABSTRACT TRUNCATED AT 250 WORDS)

O-15) - Free radical mediation of the effect of arachidonic acid, PGG2 and H+ on calcium transport by cardiac sarcoplasmic reticulum

O-15) - Free radical mediation of the effect of arachidonic acid, PGG2 and H+ on calcium transport by cardiac sarcoplasmic reticulum

Free radical mediation of leukocyte disruption of cardiac sarcoplasmic reticulum:Role of the cyclooxygenase system: M.L. Hess, T. Rowe, M. Caplan. Department of Medicine, Medical College of Virginia, Richmond, VA

Free radical mediation of leukocyte disruption of cardiac sarcoplasmic reticulum:Role of the cyclooxygenase system: M.L. Hess, T. Rowe, M. Caplan. Department of Medicine, Medical College of Virginia, Richmond, VA