Tocotrienols inhibit human glutathione S-transferase P1-1

Tocotrienols inhibit human glutathione S-transferase P1-1. van Haaften RI, Haenen GR, Evelo CT, Bast A. Department of Pharmacology and Toxicology, Faculty of Medicine, Universiteit Maastricht, The Netherlands. [email protected] Tocopherols and tocotrienols are food ingredients that are believed to have a positive effect on health. The most studied property of both groups of compounds is their antioxidant action. Previously, we found that tocopherols and diverse tocopherol derivatives can inhibit the activity of human glutathione S-transferase P1-1 (GST P1-1). In this study we found that GST P1-1 is also inhibited, in a concentration-dependent manner, by alpha- and gamma-tocotrienol. The concentration giving 50% inhibition of GST P1-1 is 1.8 +/- 0.1 microM for alpha-tocotrienol and 0.7 +/- 0.1 microM for gamma-tocotrienol. This inhibition of GST P1-1 is noncompetitive with respect to both substrates CDNB and GSH. We also examined the 3D structure of GST P1-1 for a possible tocopherol/tocotrienol binding site. The enzyme contains a very hydrophobic pit-like structure where the phytyl tail of tocopherols and tocotrienols could fit in. Binding of tocopherol and tocotrienol to this hydrophobic region might lead to bending of the 3D structure. In this way tocopherols and tocotrienols can inhibit the activity of the enzyme; this inhibition can have far-reaching implications for human

The use of vitamin supplements in self-medication

The use of vitamin supplements in self-medication. Haenen GR, Bast A. Department of Pharmacology and Toxicology, Faculty of Medicine, Maastricht University, POB 616, 6200 MD Maastricht, The Netherlands. [email protected] Supplements, frequently containing vitamins, are often taken to try to compensate for an unhealthy life style or in an attempt to maximise health or performance. As illustrated by vitamin E, fundamental issues on both the efficacy and safety of the chronic use of relatively high dosages of vitamins still need to be resolved. To recommend the application of vitamin supplements, firstly the gaps in our knowledge on these fundamental issues should be filled. Secondly, objective and scientifically sound information should be given to the public. Via diverse sources there is an uncontrolled supply of vitamins. Educating the consumer on vitamins is therefore the only way to come to a rational use of vitamin supplements in self medicatio

Cytochrome P-450 and glutathione: what is the significance of their interrelationship in lipid peroxidation?

Both cytochrome P-450 and glutathione participate in the metabolism of xenobiotics. Their interrelationship is described here, as well as current findings indicating their mutual involvement in lipid peroxidation

Ten misconceptions about antioxidants

Oxidative damage is a common cellular event involved in numerous drug toxicities. Antioxidants prevent or delay oxidative damage, and there has been extensive research into the discovery of natural and designed antioxidants. Initial excitement regarding the potential health of antioxidants has diminished. Currently, it is even claimed that increase mortality. The antioxidant pendulum appears to swing from toxic and from general panacea to insignificant ingredient. Owing to the of views towards antioxidants, nutritional recommendation ranges from increase antioxidant status in plasma to the notion that it is a useless measurement. Such views, lacking sufficient scientific support, lead to misconceptions, which in our opinion hinder the rational use of food and impedes the design and development of new antioxidant drugs. As a good opportunities might easily be missed

The toxicity of antioxidants and their metabolites

Antioxidants are used on a very large scale to try to obtain and preserve optimal health. Nutraceuticals and food supplements frequently contain huge dosages of antioxidants. It is not generally recognised that high intake of antioxidants may also have adverse effects. Three antioxidants i.e. vitamin E, beta-carotene and lipoic acid are used to illustrate general considerations on the toxicity of antioxidants. Based on the examples the following recommendations for the evaluation of the toxicity of antioxidants are made: (i) classical safety factors should not be used. (ii) Knowledge on the mechanism of the efficacy and toxicity of antioxidants should be increased. (iii) Bio-kinetic/bio-efficacy modelling might be of help to optimise dosage. (iv) When antioxidant supplementation changes into therapy, a more accurate risk/benefit analyses is warranted