Protective Effects of Brain Infarction by N-Acetylcysteine Derivatives. Issue 7 (July 2018)

• Record Type: Journal Article
• Authors: Uemura, Takeshi; Watanabe, Kenta; Ko, Kenta; Higashi, Kyohei; Kogure, Noriyuki; Kitajima, Mariko; Takayama, Hiromitsu; Takao, Koichi; Sugita, Yoshiaki; Sakamoto, Akihiko; Terui, Yusuke; Toida, Toshihiko; Kashiwagi, Keiko; Igarashi, Kazuei
• Is Part Of: Stroke. Volume 49:Issue 7(2018)
• Publication Date: 2018-07
• Subjects: acetylcysteine -- acrolein -- brain glutathione transferase -- infarction -- mice; Cerebrovascular disease -- Periodicals; Cerebral circulation -- Periodicals; 616.81
• DOI: 10.1161/STROKEAHA.118.021755
• Languages: English
• ISSNs: 0039-2499

Abstract

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. Abstract : Supplemental Digital Content is available in the text.