The specificity of thiourea, dimethylthiourea and dimethyl sulphoxide as scavengers of hydroxyl radicals. Their protection of <i>α</i>1-antiproteinase against inactivation by hypochlorous acid

Wasil, Mohammad; Halliwell, Barry; Grootveld, Martin; Moorhouse, Christopher P.; Hutchison, D. C. S.; Baum, Harold

doi:10.1042/bj2430867

Cited by 167 publications

(77 citation statements)

References 24 publications

(44 reference statements)

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“…DMSO does not react with superoxide, hydrogen peroxide or monochloramine; however, it significantly suppresses the production of these radicals (3). DMSO can react with hypochlorous acid, but the reaction is too slow (44,46). It is also a powerful scavenger of hydroxyl radicals (3,44) and inhibits leukocyte adherence (36).…”

Section: Discussionmentioning

confidence: 99%

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Protective Effects of a Culture Supernatant of Lactobacillus acidophilus and Antioxidants on Ileal Ulcer Formation in Rats Treated with a Nonsteroidal Antiinflammatory Drug

Bing

Kinouchi

Kataoka

et al. 1998

Microbiology and Immunology

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Ileal ulcers and thiobarbituric acid (TBA)‐reactive substances in the ileal mucosa were induced in rats treated with a nonsteroidal antiinflammatory drug, 5‐bromo‐2‐(4‐fluorophenyl)‐3‐(4‐methylsulfonylphenyl)thiophene (BFMeT), at a dose of 1,000 mg/kg administered with tap water as drinking water. However, the formation of ileal ulcers and TBA‐reactive substances in the ileal mucosa was repressed by giving the animals a culture supernatant of Lactobacillus acidophilus as drinking water. We measured the antioxidative activity of the culture supernatant and found that the supernatant inhibited the formation of t‐butyl hydroperoxide‐induced TBA‐reactive substances in erythrocyte membrane ghosts. Therefore, the effects of various known antioxidative compounds on the ileal ulcer formation induced by BFMeT were investigated. While α‐tocopherol, t‐butyl‐1,4‐hydroxyanisole and allopurinol did not repress ulcer formation after BFMeT treatment, ascorbic acid, dimethyl sulfoxide, glutathione and β‐carotene significantly inhibited formation. Among these compounds, ascorbic acid was the most effective. Accumulation of TBA‐reactive substances in the ileal mucosa after BFMeT treatment also decreased significantly in rats treated with ascorbic acid. In addition, the percentage of Gram‐negative rods in the ileal contents of rats treated with BFMeT and tap water was dramatically increased, but it was not increased in rats treated with BFMeT and these antioxidants. A positive correlation between the percentage of Gram‐negative rods and the number of ileal ulcers was also observed. These results suggest that lipid peroxidation mediated by oxygen radicals plays an important role in the induction of ileal ulcers by BFMeT in rats, and that lipopolysaccharide‐activated neutrophils probably produce highly reactive hypochlorous acid and hydrogen peroxide, which are inactivated by ascorbic acid and glutathione, respectively.

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Section: Discussionmentioning

confidence: 99%

“…This may be another way ulcers are induced by BFMeT. Ascorbic acid also protects a 1-antiprotease by scavenging hypochlorous acid (10,44).…”

Section: Discussionmentioning

confidence: 99%

Protective Effects of a Culture Supernatant of Lactobacillus acidophilus and Antioxidants on Ileal Ulcer Formation in Rats Treated with a Nonsteroidal Antiinflammatory Drug

Bing

Kinouchi

Kataoka

et al. 1998

Microbiology and Immunology

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“…Moreover, addition of DMTU only during reperfusion not only prevented decreases in cardiac function, but also prevented H202-dependent decreases in myocardial catalase activity after reperfusion of ischemic hearts. Although DMTU can react with H202, hydroxyl radical ( -OH), or hypochlorous acid (HOCI) in vitro (6,17), the additional finding that DMTU decreased H202-mediated inactivation of catalase in hearts from aminotriazole-treated rats further suggests that H202 participates in cardiac reperfusion injury. Moreover, * OH is usually generated from H202 in vivo (3); a contribution from HOCI seems unlikely since production of HOCI from H202 +dP dt requires neutrophil myeloperoxidase (18) and essentially no neutrophils are present in the isolated Krebs-Henseleit perfused heart.…”

Section: Discussionmentioning

confidence: 99%

Xanthine oxidase produces hydrogen peroxide which contributes to reperfusion injury of ischemic, isolated, perfused rat hearts.

Brown¹,

Terada²,

Grosso³

et al. 1988

J. Clin. Invest.

128

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Three lines of investigation indicated that hydrogen peroxide (H202) from xanthine oxidase (XO) contributes to cardiac dysfunction during reperfusion after ischemia. First, addition of dimethylthiourea (DMTU), a highly permeant 02 metabolite scavenger (but not urea) simultaneously with reperfusion improved recovery of ventricular function as assessed by ventricular developed pressure (DP), contractility (+dP/dt), and relaxation rate (-dP/dt) in isolated Krebs-Henseleit-perfused rat hearts subjected to global normothermic ischemia. Second, hearts from rats fed tungsten or treated with allopurinol had negligible XO activities (< 0.5 mU/g wet myocardium compared with > 6.0 mU/g in control hearts) and increased ventricular function after ischemia and reperfusion. Third, myocardial H202-dependent inactivation of catalase occurred after reperfusion following ischemia, but not after ischemia without reperfusion or perfusion without ischemia. In contrast, myocardial catalase did not decrease during reperfusion of ischemic hearts treated with DMTU, tungsten, or allopurinol.

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“…We investigated whether PYO was activating NF-B through effects to produce HO ⅐ by treating cells with the HO ⅐ scavenger DMSO (36). CF15 cells expressing either roGFP1 or NF-Bluciferase were treated with 100 M PYO or 100 M PYO ϩ Ն50 mM DMSO.…”

Section: Effects Of Pyo and Flagellin On Nf-b-inflammatory Signal-mentioning

confidence: 99%

Redox-independent Activation of NF-κB by Pseudomonas aeruginosa Pyocyanin in a Cystic Fibrosis Airway Epithelial Cell Line

Schwarzer

Fischer³

et al. 2008

Journal of Biological Chemistry

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The roles of the Pseudomonas aeruginosa-derived pigment pyocyanin (PYO) as an oxidant and activator of the proinflammatory transcription factor NF-B were tested in a cystic fibrosis (CF) airway epithelial cell line, CF15. 100 M PYO on its own had no effect or only small effects to activate NF-B (<1.5-fold), but PYO synergized with the TLR5 agonist flagellin. Flagellin activated NF-B 4 -20-fold, and PYO increased these activations >2. Pseudomonas aeruginosa is commonly present in lungs of cystic fibrosis (CF) 2 and immunocompromised patients (1, 2). The bacterium secretes a large number of products that contribute to virulence. These include type III-secreted exotoxins that disrupt the cytoskeleton and lyse the cells, as well as proteases, phospholipase, rhamnolipids, and hemolysin (3-8). In addition, P. aeruginosa produce and secrete the blue pigment pyocyanin (PYO), which is found in the sputum of patients with CF and bronchiectasis at concentrations up to 100 M; this is responsible for the blue-green color often observed in CF sputum (4, 5, 9, 10). PYO-deficient P. aeruginosa elicits less mortality in P. aeruginosa-mediated burn-sepsis model in mice, and PYO appears to be important for persistence of P. aeruginosa in lungs of CF patients (3, 4, 11). PYO has a multitude of effects on the physiology of epithelial cells, including inhibition or alteration of antioxidant enzymes (12, 13), ciliary function (14), cellular metabolism, and organelle H ϩ v-ATPase (2, 15). A key aspect of PYO pathology may result from its ability to trigger inflammation leading to the influx of neutrophils to the P. aeruginosa-infected region; PYO stimulates ICAM-1 and IL8 production on its own and also synergizes with IL1␤ and TNF␣ in stimulating IL8 production (16 -18). The resulting IL8 production triggers polymorphonuclear leukocyte infiltration. The polymorphonuclear leukocytes are critical for fighting infections through production of reactive oxygen species (ROS) and proteases, but these products also contribute to the tissue destruction characteristic of CF.PYO activation of IL8 production may occur through effects on cellular signaling leading to activation of the transcription factors AP-1, NF-IL6/C-EBP, and/or NF-B, which control IL8 production (19). It is widely assumed that the effects of PYO on signaling are mediated at least in part through its ability to redox cycle with cellular NADPH and/or GSH leading to the production of ROS (9,13,20,21) and oxidation of the cytosol and/or mitochondria (21,22). Experiments using the electron spin resonance method showed that PYO caused the production of superoxide (O 2 . ) but not hydroxyl radical (HO ⅐ ), indicating that O 2 . and, through the action of superoxide dismutase, H 2 O 2 might contribute to proinflammatory signaling by PYO (16). In addition, the antioxidant N-acetylcysteine and the HO ⅐ scavenger DMSO reduced the proinflammatory effects of PYO, consistent with PYO triggering inflammatory processes through its pro-oxidant effects (18). However, none of these experiment...

show abstract

The specificity of thiourea, dimethylthiourea and dimethyl sulphoxide as scavengers of hydroxyl radicals. Their protection of α1-antiproteinase against inactivation by hypochlorous acid

Cited by 167 publications

References 24 publications

Protective Effects of a Culture Supernatant of Lactobacillus acidophilus and Antioxidants on Ileal Ulcer Formation in Rats Treated with a Nonsteroidal Antiinflammatory Drug

Protective Effects of a Culture Supernatant of Lactobacillus acidophilus and Antioxidants on Ileal Ulcer Formation in Rats Treated with a Nonsteroidal Antiinflammatory Drug

Xanthine oxidase produces hydrogen peroxide which contributes to reperfusion injury of ischemic, isolated, perfused rat hearts.

Redox-independent Activation of NF-κB by Pseudomonas aeruginosa Pyocyanin in a Cystic Fibrosis Airway Epithelial Cell Line

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