The trolox analog, U-78517F, attenuates hypoxic injury in isolated cardiac myocytes.
Neonatal rat cardiac myocytes were subjected to 5 h of hypoxia (PO2 < 5 mmHg) in glucose-free, modified Tyrodes solution. Prior to hypoxic exposure, cells were pretreated for 90 min with media alone or containing the trolox analog, U-78517F, at 0.3, 1, or 3 microM. Hypoxic injury was characterized by a significant loss of sarcolemmal integrity [76 +/- 12% of the total cell fluorescence (mean +/- S.E., n = 14 cultures)] quantified by nuclear staining with the membrane-impermeant fluorophore propidium iodide. In addition, hypoxia also induced significant decreases in the intracellular content of creatine kinase (43 +/- 7%, n = 12), lactate dehydrogenase (25 +/- 5%, n = 8), adenosine 5'-triphosphate (49 +/- 12%, n = 6), and sulfhydryls (34 +/- 4%, n = 6). Sarcolemmal integrity was significantly preserved by pretreatment with 1 microM and 3 microM U-78517F which reduced propidium iodide staining below the hypoxic control value by 51 +/- 9% (n = 12) and 75 +/- 4% (n = 14, P < 0.01 v hypoxic control), respectively. Similar results were obtained in cells pretreated with alpha-tocopherol suggesting that these two compounds are equipotent at preserving the sarcolemmal integrity of cardiac myocytes exposed to hypoxia.(ABSTRACT TRUNCATED AT 250 WORDS)
Linseman
D A
DA
Upjohn Laboratories, Kalamazoo, MI 49001.
Wall
T M
TM
Hartman
J C
JC
D000818:Animals; D000831:Animals, Newborn; D000975:Antioxidants / Q000494:pharmacology; D015687:Cell Hypoxia / Q000187:drug effects; D002839:Chromans / Q000494:pharmacology*; D003402:Creatine Kinase / Q000378:metabolism; D006321:Heart / Q000187:drug effects*; D066298:In Vitro Techniques; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D015428:Myocardial Reperfusion Injury / Q000378:metabolism / Q000517:prevention & control; D010879:Piperazines / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012508:Sarcolemma / Q000187:drug effects / Q000378:metabolism; D013438:Sulfhydryl Compounds / Q000378:metabolism
D000975:Antioxidants; D002839:Chromans; D010879:Piperazines; D013438:Sulfhydryl Compounds; C066382:U 78517F; D007770:L-Lactate Dehydrogenase; D003402:Creatine Kinase; C010643:6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid