[Effects of ascorbic acid on the free radical formations of isoniazid and its metabolites].
By the use of electron spin resonance (ESR) spectroscopy and of spin-trapping technique, the effects of ascorbic acid on the formation of the free radical intermediates due to isoniazid (INAH) and its metabolites were investigated with a microsomal system. When alpha-(4-pyridyl 1-oxide)-N-tert butylnitrone (4-POBN) was used as a spin trapping agent, the ESR signal due to hydrazine (Hy) was formed to be most intensive among others. Therefore, it was presumed that Hy is a potent intermediate to cause an INAH-induced hepatic injury. In the presence of ascorbic acid (AA), the free radical formation of Hy, INAH and acetyl hydrazine was significantly inhibited, suggesting that AA may affect the INAH-hepatitis. By the addition of inhibitors of cytochrome P-450 like metyrapone and CO, the generation of the radical from Hy decreased, confirming that the radical is formed by the cytochrome P-450 dependent microsome systems. The 4-POBN-trapped radical species generated from Hy was presumed to be the hydrazyl radical by the results of mass spectrometry.
Matsuki
Y
Y
Faculty of Pharmaceutical Sciences, University of Tokushima, Japan.
Akazawa
M
M
Tsuchiya
K
K
Sakurai
H
H
Kiwada
H
H
Goromaru
T
T
D000818:Animals; D001205:Ascorbic Acid / Q000494:pharmacology* / Q000627:therapeutic use; D056486:Chemical and Drug Induced Liver Injury / Q000517:prevention & control; D016166:Free Radical Scavengers; D005609:Free Radicals / Q000378:metabolism; D006834:Hydrazines / Q000378:metabolism; D066298:In Vitro Techniques; D007538:Isoniazid / Q000009:adverse effects / Q000378:metabolism*; D008862:Microsomes, Liver / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains
D016166:Free Radical Scavengers; D005609:Free Radicals; D006834:Hydrazines; C029424:hydrazine; D001205:Ascorbic Acid; D007538:Isoniazid