Iron-initiated tissue oxidation: lipid peroxidation, vitamin E destruction and protein thiol oxidation. Inhibition by a novel antioxidant, U-78517F.

Oxidative injury was initiated by addition of ferrous ammonium sulfate (FAS) to a suspension of whole rat brain homogenate in Krebs buffer. After FAS addition, tissue vitamin E dropped sharply over a 30-sec interval and then recovered marginally for 5 min. After 5 min, vitamin E levels dropped to a low and constant level. Also after 5 min, TBARS (thiobarbituric acid reactive substances, a color test for lipid peroxidation) showed a statistically significant (P < or = 0.05) increase that continued through the remainder of the 30-min experiment. Reduced protein thiols decreased significantly (P < or = 0.05) at 15 min post FAS addition. This suggests that, in this model of iron-initiated lipid peroxidation (LP), the endogenous antioxidant vitamin E is first depleted before membrane lipids and membrane bound proteins show evidence of oxidative injury. A novel antioxidant, U-78517F, inhibited the destruction of vitamin E, LP and protein thiol oxidation in this model. The efficacy of the compound after different times of addition is described.