Prevention of cumene hydroperoxide induced oxidative stress in cultured neonatal rat myocytes by scavengers and enzyme inhibitors

Journal of Molecular and Cellular Cardiology
M Persoon-RothertArnoud van der Laarse

Abstract

Oxidative stress induced by cumene hydroperoxide was studied in cultured neonatal rat myocytes. A progressive increase of irreversible cell injury as determined by leakage of the cytoplastic enzyme alpha-hydroxybutyrate dehydrogenase (alpha-HBDH) from the cells was noted at concentrations ranging from 25-100 microM cumene hydroperoxide (incubation time 90 min). Cumene hydroperoxide-induced damage was reduced or prevented by several compounds: the application of Trolox C, a water-soluble vitamin E analogue, and of phospholipase A2 inhibitors chlorpromazine and (to a lesser extent) quinacrine prevented alpha-HBDH release. ICRF-159, a chelator of divalent cations, ascorbic acid, a potent antioxidant, and the cysteine protease inhibitor leupeptin did not reduce the cumene hydroperoxide-induced cytotoxicity. Detoxification of hydroperoxides by the glutathione peroxidase system results in an increased flux through the pentose phosphate shunt and loss of NADPH. Glucose inhibited the cumene hydroperoxide-induced alpha-HBDH release, probably by replenishing NADPH. These results indicate that cumene hydroperoxide, after exhaustion of the glutathione system, induces irreversible injury in cultured myocytes by a mechanism that depends to a...Continue Reading

Citations

Sep 1, 1995·Journal of Molecular and Cellular Cardiology·W F TzengT J Chiou
Sep 18, 2004·American Journal of Respiratory and Critical Care Medicine·Jenna L BettersScott K Powers
Oct 3, 2007·Pflügers Archiv : European journal of physiology·M H M HesselA van der Laarse
Aug 30, 2008·Experimental and Molecular Pathology·M H M HesselA van der Laarse
Jul 20, 2010·Toxicology·Parvinder KaurTore Syversen

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