Effect of alpha-tocopherol and di-butyl-hydroxytoluene (BHT) on UV-A-induced photobinding of 8-methoxypsoralen to Wistar rat epidermal biomacromolecules in vivo

Publisher Website
Google Scholar
Abstract
The possible formation of singlet oxygen via photoexcited psoralens has been associated with the occurrence of, amongst others, erythema. Therefore it has been suggested to combine PUVA with the topical or systemic administration of antioxidants. However, the effect of these antioxidants on the photobinding of psoralens to DNA, which is held responsible for the anti-proliferative effect, should be taken into account. In the present study the effect of two phenolic antioxidants, alpha-tocopherol (AT) and butylated hydroxytoluene (BHT), on the in vivo photobinding of 8-methoxypsoralen (8-MOP) to not only epidermal DNA, but also proteins and lipids was determined. After topical application of an ethanolic antioxidant solution onto the shaven skin of Wistar rats, labeled 8-MOP was applied using the same solvent. After this the rats were exposed to UV-A. By separating epidermal lipids, DNA/RNA and proteins by a selective extraction method, irreversible binding of 8-MOP to each of these biomacromolecules was determined. Both AT and BHT caused a decrease in the photobinding of 8-MOP to epidermal DNA and proteins. To investigate the underlying mechanism of this protection, the effect of AT was compared with that of AT-acetate. It also proved helpful to study the effects of the antiooxidants on the photobinding of another photosensitizer, namely chlorpromazine. From these experiments it was concluded that AT and BHT affect 8-MOP photobinding by quenching reactive 8-MOP intermediates, involving the phenolic hydroxyl group of the antioxidants. BHT offered protection against lipid binding of 8-MOP but AT, especially at high concentrations, enhanced the UV-A-induced binding of 8-MOP to lipids. This is noteworthy with respect to the current interest in the role of 8-MOP-lipid adducts in PUVA therapy.

This publication has 22 references indexed in Scilit: