IN-VIVO DETECTION OF ANTHRALIN-DERIVED FREE-RADICALS IN THE SKIN OF HAIRLESS MICE BY LOW-FREQUENCY ELECTRON-PARAMAGNETIC-RESONANCE SPECTROSCOPY

Free radicals were directly detected in vivo in the skin of hairless m ice by low-frequency electron paramagnetic resonance spectroscopy afte r topical application of anthralin under pertinent therapeutic conditi ons. The electron paramagnetic resonance signal intensity increased st eadily, reaching a maximum after about 1 d and decreased slowly in the following days, probably because of desquamation of the skin. We conc lude from the spectroscopic features (single line with a line width of 6 gauss; g = 2.0036) and from the pharmacokinetic pattern that the ob served signal arises from the final products of anthralin metabolism ( ether-insoluble polymeric structures- ''anthralin brown''). Two potent ial antioxidants, vitamin E and the spin trap tert-butylphenylnitrone, decreased the amount of the anthralin-derived radical that was formed . Neither vitamin E radicals nor tert-butylphenylnitrone spin adducts were observed. We suggest that electron paramagnetic resonance is a va luable tool for the noninvasive and direct in vivo monitoring of drug- induced radical formation in the skin under therapeutic conditions.