Free Radical Theory of Aging: Inhibition of Amyloidosis in Mice by Antioxidants; Possible Mechanism*

作者：Denham Harman, DENNIS E. EDDY, JAMES NOFFSINGER · 发表于：Journal of the American Geriatrics Society · 年份：1976 · DOI：10.1111/j.1532-5415.1976.tb06780.x · 被引用次数：54 · 研究领域：Proteins in Food Systems、Alzheimer's disease research and treatments、Biochemical Acid Research Studies

The antioxidants, alpha-tocopherol acetate and a quinolone derivative (Santoquin), inhibited the development of amyloidosis when added to the diet of casein-injected C3HeB/FeJ male mice. Santoquin, and to a lesser extent butylated hydroxytoluene (BHT), also depressed the appearance of a plasma protein fraction in these mice; the effect of alpha-tocopherol was not determined. Consideration of the current knowledge of amyloid, in the light of these antioxidant studies, prompted the following hypothesis. Amyloidosis is largely the result of an enhanced rate of oxidative degradation of a connective-tissue glycoprotein(s) coupled with oxidative/enzymatic changes in the plasma, both of the tissue-derived substances and of immunoglobulins, to form the amyloid fibril protein subunits (AL and AA) which subsequently aggreagate to form the amyloid fibrils.