TITLE

AN IN VITRO AND IN VIVO INVESTIGATION OF THE PHOTOTOXIC EFFECT AND ITS AMELIORATION WITH RADIOPROTECTIVE COMPOUNDS

AUTHOR(S)
Copeland, Edmund S.; Grenan, Marie M.; Yang, George C.
PUB. DATE
May 1975
SOURCE
Journal of Investigative Dermatology;May75, Vol. 64 Issue 5, p349
SOURCE TYPE
Academic Journal
DOC. TYPE
Article
ABSTRACT
Electron spin resonance spectroscopy has been used to demonstrate that the phototoxic antimalarial drug, 6,8-dichloro-2-phenyl-α-2-piperidinylquinolinemethanol (WR 7930), when irradiated with long-wave ultraviolet (UV) light (A > 320 nm) while held in a glassy matrix at 73°K, enters a triplet state and releases hydrogen atoms in its environment. The steady-state concentration of triplet WR 7930 molecules and of hydrogen atoms is reduced 2 to 3 times when mercaptoethylamine (MEA) is also present in the UV-irradiated glass. Organosulfur radicals form on MEA while hydrogen atoms and triplet-state molecules are reduced in number. Hydrogen atoms and triplet WR 7930 molecules are considered as mediators of the phototoxicity of the antimalarial drug. Thus, hydrogen atom scavanging and chemical quenching of the triplet state are possible mechanisms by which protection against phototoxic effects could be gained. Protection is demonstrated in mice receiving 20 mg per kg WR 7930 intraperitoneally and exposed to long-wave UV for 20 hr when the radioprotective aminothiol-forming compound, 2-(3-aminopropylamino)ethyl dihydrogen phosphorothioate (WR 2721), is administered at 400 mg per kg immediately before irradiation. When no protective drug is administered concurrently, WR 7930 administration results in intense erythema, edema, and eventual necrosis of ear tissues.
ACCESSION #
12512287

 

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