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Free radical induced lipid peroxidation and alteration of calcium transients in cultured cardiac myocytes.
Toraason M; Breitenstein M; Heinroth-Heinroth I; Hoffmann P
Toxicologist 1992 Feb; 12(1):70
Oxygen derived free radicals are generated in the myocardium during ischemic reperfusion injury, and free radical generating systems are utilized in vitro to mimic this injury. Two key events resulting from oxidative stress in the myocardium are lipid peroxidation and alteration in intracellular calcium ([Ca+2]i). We investigated the interdependency of these two effects by measuring [Ca+2]i with fura-2, lipid peroxidation by release of thiobarbaturic acid reactive substances (TBARS), and cytotoxicity by leakage of lactate dehydrogenase (LDH). Oxidative stress was induced in iron-transferrin supplemented myocytes with 100 microM H2O2. Within 5 min of exposure, H2O2 increased systolic [Ca+2 ]i in electrically paced myocytes (60 v, 1 Hz, 10 msec), which was followed by an increase in diastolic [Ca+2]i. These effects were reversed by washout of H2O2. In non-paced quiescent myocytes, a small increase in basal [Ca+21j occurred (10% peak systolic Ca) within 5 min of H2O2 exposure, which could be prevented by simultaneous perfusion with 1 microM verapamil or nominal calcium buffer. After 20 min of exposure to H2O2, myocytes (paced or non-paced) underwent nonreversible contracture caused by high [Ca+2]I (>100% peak systolic Ca). A 1 hr exposure to H2O2 caused TBARS and LDH release. The post 20 min exposure effects were not prevented by verapamil or by nominal calcium buffer. Results indicate that early alterations in myocyte [Ca+2]i transients are reversible and dependent on extracellular calcium flux. Prolonged exposure to H2O2 leads to hypercontracture, lipid peroxidation, and cell death; and these effects are not dependent on extracellular calcium.
Free-radicals; Lipid-peroxidation; Cell-damage; Cell-function; Cellular-reactions; Cardiovascular-function; Cardiovascular-system; Heart
Issue of Publication
The Toxicologist. Society of Toxicology 31st Annual Meeting, February 23-27,1992, Seattle, Washingtion
Page last reviewed: September 2, 2020
Content source: National Institute for Occupational Safety and Health Education and Information Division