Biomedical subjects

K M Toth

Publications and source records attributed to K M Toth.

5 recordsLinked to original sources

PubMed1989

Dimethylthiourea prevents hydrogen peroxide and neutrophil mediated damage to lung endothelial cells in vitro and disappears in the process.

Dimethylthiourea (DMTU) progressively disappeared following reaction with increasing amounts of hydrogen peroxide (H2O2) in vitro. DMTU disappearance following reaction with H2O2 was inhibited by addition of catalase, but not aminotriazole-inactivated catalase (AMT-catalase), superoxide dismutase (SOD), mannitol, benzoate or dimethyl sulfoxide (DMSO) in vitro. By comparison, DMTU disappearance did not occur following addition of histamine, oleic acid, elastase, trypsin or leukotrienes in vitro. Addition of DMTU also decreased H2O2-mediated injury to bovine pulmonary artery endothelial cells (as reflected by LDH release) and DMTU disappeared according to both added amounts of H2O2 and corresponding degrees of injury. DMTU disappearance was also relatively specific for reaction with H2O2 in suspensions of endothelial cells where it was prevented by addition of catalase, but not AMT-catalase or SOD and did not occur following sonication or treatment with elastase, trypsin or leukotrienes. Addition of washed human erythrocytes (RBC) also prevented both H2O2 mediated injury and corresponding DMTU decreases in suspensions of endothelial cells. In addition, phorbol myristate acetate (PMA) and normal neutrophils, but not O2 metabolite deficient neutrophils from patients with chronic granulomatous disease (CGD), caused DMTU disappearance in vitro which was decreased by simultaneous addition of catalase, but not SOD, sodium benzoate or DMSO. Finally, addition of normal neutrophils (but not CGD neutrophils) and PMA caused DMTU disappearance and increased the concentrations of the stable prostacyclin derivative (PGF1 alpha) in supernatants of endothelial cell suspensions. In parallel, DMTU also decreased PMA and neutrophil-mediated PGF1 alpha increases in supernatants from endothelial cell monolayers. Our results indicate that DMTU can decrease H2O2 or neutrophil mediated injury to endothelial cells and that simultaneous measurement of DMTU disappearance can be used to improve assessment of the presence and toxicity of H2O2 as well as the H2O2 inactivating ability of scavengers, such as RBC, in biological systems.

Animals↗

PubMed1989

Erythrocytes decrease myocardial hydrogen peroxide levels and reperfusion injury.

Reperfusion with untreated, carbon monoxide-treated, or glutaraldehyde-fixed human erythrocytes (RBC) increased ventricular function and decreased myocardial hydrogen peroxide (H2O2) levels [assessed by H2O2-dependent aminotriazole (AMT) inactivation of myocardial catalase activities] of ischemic, isolated rat hearts. In contrast, reperfusion with RBC that lacked catalase (AMT treated) and/or glutathione (N-ethylmaleimide treated) did not increase ventricular function or decrease myocardial H2O2 levels as much as reperfusion with untreated RBC. By comparison, reperfusion with superoxide dismutase-depleted (diethyldithiocarbamate-treated) or anion channel-inhibited (diisothiocyanodisulfonic acid stilbene-treated) RBC increased ventricular function and decreased myocardial H2O2 levels the same as untreated RBC. The results suggest that catalase and/or glutathione in intact RBC can decrease endogenously generated H2O2 and related reperfusion injury in ischemic, isolated perfused hearts.

4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid↗

PubMed1989

Blood sulfhydryl level increases during hyperoxia: a marker of oxidant lung injury.

Blood acid-soluble sulfhydryl, but not glutathione (GSH), levels increased during the development of acute edematous lung injury in rats exposed to normobaric hyperoxia for 48 h or more. A relationship between increases in blood sulfhydryl levels, lung injury, and O2 metabolite generation during exposure to hyperoxia was suggested by two observations. First, increases in blood sulfhydryl levels occurred simultaneously with increases in lung oxidized glutathione (GSSG) levels and lung GSSG-to-GSH ratios (GSSG/GSH). Second, hyperoxia-induced increases in blood sulfhydryl levels, blood hematocrits, pleural effusion volumes, lung GSSG levels, and lung GSSG/GSH were decreased by pretreating rats with dimethylthiourea (DMTU), an O2 metabolite scavenger. Our findings indicate that exposure of rats to hyperoxia increases blood acid-soluble sulfhydryl levels in vivo and that increases in blood sulfhydryl levels may provide an accessible marker of increased oxidant exposure and/or oxidant-mediated lung injury.

Animals↗

PubMed1986

Erythrocytes from cigarette smokers contain more glutathione and catalase and protect endothelial cells from hydrogen peroxide better than do erythrocytes from nonsmokers.

Recent observations regarding the ability of intracellular erythrocyte (RBC) antioxidants to decrease O2 metabolite-mediated injury to lung tissues has prompted interest in the RBC antioxidants of patients with lung disease. We found that RBC from 14 healthy, age- and gender-matched cigarette smokers contained more (p less than 0.05) glutathione (6.3 +/- 0.4 microM/g Hgb versus 5.0 +/- 0.3 microM/g Hgb) and catalase (249,533 +/- 8,307 units/g Hgb versus 222,617 +/- 7,180 units/g Hgb) than did RBC from nonsmokers. In contrast, RBC from cigarette smokers and nonsmokers contained the same activities of glutathione peroxidase (21.4 +/- 1.2 units/g Hgb versus 20.4 +/- 5.5 units/g Hgb). RBC from cigarette smokers also protected bovine pulmonary artery endothelial cells in culture from hydrogen peroxide (H2O2) better (p less than 0.005) than did RBC from nonsmokers (52.1 +/- 6.1% protection versus 31.9 +/- 5.7% protection). The results suggest that alterations in RBC antioxidants may reflect exposure and/or affect susceptibility to oxidant-induced injury.

Animals↗

PubMed1985

HEPES may stimulate cultured endothelial cells to make growth-retarding oxygen metabolites.

Zwitterion buffers are often used to modulate the pH of cell culture medium but their effect on cultured cells is controversial. We found that addition of 4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid (HEPES) caused superoxide dismutase (SOD) inhibitable increases in nitroblue tetrazolium dye reduction and SOD and catalase inhibitable decreases in the growth of cultured bovine pulmonary artery endothelial cells. The findings suggest that HEPES stimulates endothelial cells to make toxic oxygen metabolites that contribute to decreased cell growth.

Animals↗