The effect of vitamin E analogues and long hydrocarbon chain compounds on calcium-induced muscle damage. A novel role for alpha-tocopherol?
Previous studies have demonstrated that supplemental alpha-tocopherol inhibited calcium-induced cytosolic enzyme efflux from normal rat skeletal muscles incubated in vitro and suggested that the protective action was mediated by the phytyl chain of alpha-tocopherol [1]. In order to investigate this further a number of hydrocarbon chain analogues of tocopherol (7,8-dimethyl tocol, 5,7-dimethyl tocol, tocol, alpha-tocotrienol, alpha-tocopherol [10], vitamin K1, vitamin K1 [10], vitamin K1 diacetate, vitamin K2 [20], phytyl ubiquinone and retinol) were tested for any ability to inhibit calcium ionophore, A23187, induced creatine kinase (CK) enzyme efflux. Some compounds were found to be very effective inhibitors and comparison of their structures and ability to inhibit TBARS production in muscle homogenates revealed that the effects did not appear related to antioxidant capacity or chromanol methyl groups, but rather the length and structure of the hydrocarbon chain was the important mediator of the effects seen.
Department of Medicine, University of Liverpool, U.K.
J
J
Phoenix
R H
RH
Edwards
M J
MJ
Jackson
D000818:Animals; D000001:Calcimycin / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D002118:Calcium / Q000494:pharmacology*; D003402:Creatine Kinase / Q000378:metabolism*; D003600:Cytosol / Q000201:enzymology; D005260:Female; D007700:Kinetics; D015227:Lipid Peroxidation / Q000187:drug effects; D009132:Muscles / Q000187:drug effects* / Q000201:enzymology; D051381:Rats; D011919:Rats, Inbred Strains; D013329:Structure-Activity Relationship; D014810:Vitamin E / Q000031:analogs & derivatives* / Q000494:pharmacology
D014810:Vitamin E; D000001:Calcimycin; D003402:Creatine Kinase; D002118:Calcium