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Poloxamer 188 Protects Isolated Adult Mouse Cardiomyocytes from Reoxygenation Injury.
- Source :
-
Pharmacology research & perspectives [Pharmacol Res Perspect] 2020 Dec; Vol. 8 (6), pp. e00639. - Publication Year :
- 2020
-
Abstract
- Reperfusion injury is a complex pathological event involving processes that can lead to further disruption of the cell membrane and function following an ischemic event. Return of blood flow allows for the needed reperfusion; however, for a period of time before remaining viable cells stabilize, reperfusion results in additional cellular injury. In cardiomyocytes, loss of membrane integrity allows abnormal influx of extracellular calcium, leading to hyper-contracture and cell death. Methods to improve the membrane integrity of cardiomyocytes overwhelmed by pathological disruptions, such as reperfusion injury, are needed to prevent cell death, because of the myocardium's limited ability to regenerate. Research has shown administration of the copolymer P(oloxamer) 188 before ischemia/reperfusion can protect cardiomyocytes through membrane stabilization. This study sought to determine whether the administration of P188 at the beginning of the clinically more relevant time of reperfusion after ischemia will attenuate any additional damage to cardiomyocytes by stabilizing membrane integrity to allow the cells to maintain function. Using an in-vitro cardiomyocyte model subjected to hypoxia/reoxygenation to simulate ischemia/reperfusion injury, we show that reoxygenation significantly potentiates the injury caused by hypoxia itself. P188, with its unique combination of hydrophobic and hydrophilic chemical properties, and only delivered at the beginning of reoxygenation, dose-dependently protected cardiomyocytes from injury due to reoxygenation by repairing cell membranes, decreasing calcium influx, and maintaining cellular morphology. Our study also shows the hydrophobic portion of P188 is necessary for the stabilization of cell membrane integrity in providing protection to cardiomyocytes against reoxygenation injury.<br /> (© 2020 The Authors. Pharmacology Research & Perspectives published by British Pharmacological Society and American Society for Pharmacology and Experimental Therapeutics and John Wiley & Sons Ltd. This article has been contributed to by US Government employees and their work is in the public domain in the USA.)
- Subjects :
- Animals
Cells, Cultured
Dose-Response Relationship, Drug
Excipients pharmacology
Excipients therapeutic use
Male
Mice
Mice, Inbred C57BL
Myocardial Reperfusion Injury prevention & control
Myocytes, Cardiac pathology
Poloxamer therapeutic use
Myocardial Reperfusion Injury metabolism
Myocytes, Cardiac drug effects
Myocytes, Cardiac metabolism
Poloxamer pharmacology
Subjects
Details
- Language :
- English
- ISSN :
- 2052-1707
- Volume :
- 8
- Issue :
- 6
- Database :
- MEDLINE
- Journal :
- Pharmacology research & perspectives
- Publication Type :
- Academic Journal
- Accession number :
- 33073927
- Full Text :
- https://doi.org/10.1002/prp2.639