Protective Effects of Brain Infarction by <i>N</i> -Acetylcysteine Derivatives

<jats:sec> <jats:title>Background and Purpose—</jats:title> <jats:p> We recently found that acrolein (CH <jats:sub>2</jats:sub> =CH-CHO) is more strongly involved in brain infarction compared with reactive oxygen species. In this study, we looked for acrolein scavengers with less side effects. </jats:p> </jats:sec> <jats:sec> <jats:title>Methods—</jats:title> <jats:p> Photochemically induced thrombosis model mice were prepared by injection of Rose Bengal. Effects of <jats:italic>N</jats:italic> -acetylcysteine (NAC) derivatives on brain infarction were evaluated using the public domain National Institutes of Health image program. </jats:p> </jats:sec> <jats:sec> <jats:title>Results—</jats:title> <jats:p> NAC, NAC ethyl ester, and NAC benzyl ester (150 mg/kg) were administered intraperitoneally at the time of induction of ischemia, or these NAC derivatives (50 mg/kg) were administered 3× at 24-h intervals before induction of ischemia and 1 more administration at the time of induction of ischemia. The size of brain infarction decreased in the order NAC benzyl ester>NAC ethyl ester>NAC in both experimental conditions. Detoxification of acrolein occurred through conjugation of acrolein with glutathione, which was catalyzed by glutathione <jats:italic>S</jats:italic> -transferases, rather than direct conjugation between acrolein and NAC derivatives. The level of glutathione <jats:italic>S</jats:italic> -transferases at the locus of brain infarction was in the order of administration of NAC benzyl ester>NAC ethyl ester>NAC>no NAC derivatives, suggesting that NAC derivatives stabilize glutathione <jats:italic>S</jats:italic> -transferases. </jats:p> </jats:sec> <jats:sec> <jats:title>Conclusions—</jats:title> <jats:p> The results indicate that detoxification of acrolein by NAC derivatives is caused through glutathione conjugation with acrolein catalyzed by glutathione <jats:italic>S</jats:italic> -transferases, which can be stabilized by NAC derivatives. This is a new concept of acrolein detoxification by NAC derivatives. </jats:p> </jats:sec>