In vitro and in vivo investigation of the phototoxic effect and its amerlioration with radioprotective compounds. [6,8-dichloro-2-phenyl-. cap alpha. -2-piperidinylquinolinemethanol]
Electron spin resonance spectroscopy has been used to demonstrate that the phototoxic antimalarial drug, 6,8-dichloro-2-phenyl-..cap alpha..-2-piperidinylquinolinemethanol (WR 7930), when irradiated with long-wave ultraviolet (uv) light (lambda greater than 320 nm) while held in a glassy matrix at 73/sup 0/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 scavenging 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 erythemia, edema, and eventual necrosis of ear tissues.
- Research Organization:
- Walter Reed Army Inst. of Research, Washington, DC
- OSTI ID:
- 7190230
- Journal Information:
- J. Invest. Dermatol.; (United States), Journal Name: J. Invest. Dermatol.; (United States) Vol. 64:5; ISSN JIDEA
- Country of Publication:
- United States
- Language:
- English
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Related Subjects
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
AMINES
ANIMALS
CHEMICAL RADIATION EFFECTS
CHEMISTRY
CRYOGENIC FLUIDS
DRUGS
ELECTROMAGNETIC RADIATION
ELECTRON SPIN RESONANCE
ELEMENTS
FLUIDS
HYDROGEN
MAGNETIC RESONANCE
MAMMALS
MEA
MICE
MOLECULES
NONMETALS
ORGANIC COMPOUNDS
ORGANIC SULFUR COMPOUNDS
RADIATION CHEMISTRY
RADIATION EFFECTS
RADIATIONS
RADIOPROTECTIVE SUBSTANCES
RADIOSENSITIVITY EFFECTS
RESONANCE
RESPONSE MODIFYING FACTORS
RODENTS
SPECTROSCOPY
THIOLS
TOXICITY
ULTRAVIOLET RADIATION
VERTEBRATES