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Cellular mechanism of U78517F in the protection of porcine coronary artery endothelial cells from oxygen radical‐induced damage
Author(s) -
Maeda Kaori,
Kimura Masaaki,
Hayashi Shigehiro
Publication year - 1993
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1993.tb13508.x
Subject(s) - lactate dehydrogenase , lipid peroxidation , xanthine oxidase , chemistry , malondialdehyde , superoxide dismutase , biochemistry , catalase , extracellular , hydroxyl radical , pharmacology , radical , oxidative stress , medicine , enzyme
1 The aim of this study was to clarify the role of lipid peroxidation in cellular injury as assessed by lactate dehydrogenase (LDH) release from cultured coronary artery endothelial cells of the pig. Cells exposed to H 2 O 2 at concentrations of 0.1 to 20 m m or to a xanthine and xanthine oxidase (X/XO) reaction mixture released LDH into the medium. Significant release from X/XO‐treated cells took place with a delay of 2 h. 2 Superoxide dismutase (SOD), catalase or dimethylthiourea attenuated the release of LDH from X/XO‐treated cells. Similarly the putative inhibitor of lipid peroxidation, U78517F attenuated the release of LDH by X/XO with an IC 50 of 0.08 μ m . 3 H 2 O 2 was continuously produced by the addition of X/XO to the medium alone. However, in the presence of endothelial cells, H 2 O 2 was eliminated at 1 h. U78517F had no effect on either process. 4 The oxygen radical‐induced release of LDH was associated with malondialdehyde (MDA) formation. U78517F inhibited the formation of MDA with an IC 50 of 0.27 μ m . 5 Reduction of the Ca 2+ concentration in the incubation medium from 1.6 m m to 0.016 m m markedly attenuated the release of LDH from endothelial cells. Nifedipine (1 μ m ) did not attenuate the LDH release from the cells. 6 It is likely that porcine coronary artery endothelial cells can be thus injured by oxygen radicals presumably through hydroxyl radicals formed and consequent lipid peroxidation, and that the extracellular Ca 2+ concentration plays an important role in the genesis of such endothelial cell damage.