Oxygen radical-mediated injury of myocytes-protection by propranolol.
UIe effects of propranolol and atenolol on free radical mediated injury in myocytes were examined. Freshly isolated adult canine myocytes were incubated with a superoxide generating (from dihydroxyfumarate) and Fe-catalyzed free radical system. Exposure of the myocytes to free radicals for 20 min resulted in more than a 5-fold increase in thiobarbituric acid reactant (peroxide) formation and elevated levels of lactate dehydrogenase (LDH) activity released into the media compared to controls. Ultrastructurally, severe sarcolemmal damage, mitochondrial and myofibril derangements were evident. At 40 min, cellular viability (trypan blue exclusion) in the samples exposed to free radicals decreased to about one-third of controls; concomitantly, major losses in total cellular phospholipids occurred. When the cells were pretreated with 200 microM propranolol before the addition of free radicals, both peroxide formation and increased LDH release were inhibited; in agreement, complete ultrastructural preservation was observed. In addition, the subsequent losses in cellular viability and phospholipids were prevented. For comparison, the more water soluble beta-blocker, atenolol at 200 microM was shown ineffective in providing significant protection against the induced injury. The results suggest that propranolol may provide antiperoxidative protection to myocytes when elevated levels of free radicals are present.
Mak
I T
IT
Department of Medicine, George Washington University Medical Center, Washington, DC 20037.
Kramer
J H
JH
Freedman
A M
AM
Tse
S Y
SY
Weglicki
W B
WB
D000818:Animals; D002470:Cell Survival / Q000187:drug effects; D004285:Dogs; D005609:Free Radicals; D006321:Heart / Q000187:drug effects; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects*; D008854:Microscopy, Electron; D009206:Myocardium / Q000166:cytology* / Q000378:metabolism / Q000648:ultrastructure; D010100:Oxygen / Q000502:physiology*; D010743:Phospholipids / Q000378:metabolism; D011433:Propranolol / Q000494:pharmacology*
D005609:Free Radicals; D010743:Phospholipids; D011433:Propranolol; D007770:L-Lactate Dehydrogenase; D010100:Oxygen