Effects of glucose, Trolox-C, and glutathione disulphide on lipid peroxidation and cell death induced by oxidant stress in rat heart.
OBJECTIVE
The aim was to find effective protection of myocytes against peroxide induced damage in terms of preservation of contractile activity, protection against lipid peroxidation, and protection against cell death.


METHODS
The components of the glutathione redox cycle, the production of malondialdehyde, cell contractions, and enzyme release from myocytes were measured in cultured neonatal rat heart cells before and after administration of cumene hydroperoxide, 80 mumol.litre-1. The protective action was tested of (1) glucose (10 mmol.litre-1) which stimulates the production of NADPH; (2) Trolox-C (0.16 mmol.litre-1) which is a water soluble analogue of alpha tocopherol and a scavenger of free radicals; and (3) GSSG (0.6 mmol.litre-1) which increases the intracellular concentrations of GSH and GSSG.


RESULTS
Although the three substances tested were equally effective in reducing the formation of malondialdehyde, exogenous GSSG afforded only slight protection against cumene hydroperoxide induced cell death, whereas glucose and Trolox-C were highly effective protectors. The depressant effect of cumene hydroperoxide on beating frequency was not influenced by preincubation with GSSG, nor by coadministration of glucose, but Trolox-C was able to diminish the negative chronotropic action of cumene hydroperoxide.


CONCLUSIONS
Effective protection against cumene hydroperoxide induced lipid peroxidation is not associated per se with effective protection against cumene hydroperoxide induced loss of beating frequency and cell death.
Le
C T
CT
Department of Cardiology, University Hospital, Leiden, The Netherlands.
Hollaar
L
L
van der Valk
E J
EJ
van der Laarse
A
A
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D001555:Benzene Derivatives / Q000494:pharmacology; D016923:Cell Death / Q000187:drug effects; D002478:Cells, Cultured; D002839:Chromans / Q000494:pharmacology*; D005947:Glucose / Q000494:pharmacology*; D005978:Glutathione / Q000031:analogs & derivatives* / Q000494:pharmacology; D019803:Glutathione Disulfide; D006321:Heart / Q000187:drug effects*; D015227:Lipid Peroxidation / Q000187:drug effects*; D008315:Malondialdehyde / Q000378:metabolism; D009200:Myocardial Contraction / Q000187:drug effects; D009206:Myocardium / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains
D000975:Antioxidants; D001555:Benzene Derivatives; D002839:Chromans; D008315:Malondialdehyde; D005978:Glutathione; D005947:Glucose; C007164:cumene hydroperoxide; C010643:6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid; D019803:Glutathione Disulfide