Protective Effects of Brain Infarction by N-Acetylcysteine Derivatives.
Stroke
; 49(7): 1727-1733, 2018 07.
Article
in En
| MEDLINE
| ID: mdl-29866754
ABSTRACT
BACKGROUND AND PURPOSE:
We recently found that acrolein (CH2=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.METHODS:
Photochemically induced thrombosis model mice were prepared by injection of Rose Bengal. Effects of N-acetylcysteine (NAC) derivatives on brain infarction were evaluated using the public domain National Institutes of Health image program.RESULTS:
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 S-transferases, rather than direct conjugation between acrolein and NAC derivatives. The level of glutathione S-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 S-transferases.CONCLUSIONS:
The results indicate that detoxification of acrolein by NAC derivatives is caused through glutathione conjugation with acrolein catalyzed by glutathione S-transferases, which can be stabilized by NAC derivatives. This is a new concept of acrolein detoxification by NAC derivatives.Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Acetylcysteine
/
Brain
/
Oxidative Stress
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Neuroprotective Agents
/
Brain Infarction
Limits:
Animals
Language:
En
Journal:
Stroke
Year:
2018
Document type:
Article