Effect of the spin-trapping compound N-tert-butyl-alpha-phenylnitrone on protein oxidation and life span.

N-tert-Butyl-alpha-phenylnitrone (PBN), a lipophilic spin-trapping compound, has been reported to decrease the concentration of protein carbonyls, the products of protein oxidation, in the brain of old gerbils to virtually the level found in the young gerbils (Carney, J. M., et al. (1991) Proc. Natl. Acad. Sci. USA 88, 3633-3636). The validity of this finding as well as that of the commonly used 2,4-dinitrophenylhydrazine procedure for the measurement of protein carbonyls was recently called into question by Cao and Cutler ((1995) Arch. Biochem. Biophys. 320, 106-114). The objective of the present study was to examine some of the relevant issues such as (a) whether the original findings on the effects of PBN can be confirmed, (b) whether similar effects of PBN occur in other species and tissues, and (c) whether PBN affects the life span of animals. Results of this study provide confirmation of the original finding that PBN indeed causes a decrease in protein carbonyl content in the gerbil brain cortex. However, a similar effect is not observed in the gerbil heart or the mouse brain cortex. Effects of PBN on protein carbonyls are thus variable depending upon tissue and species. PBN administration did not extend the life span of houseflies and at relatively high concentrations it was found to be toxic.