Therapeutic Effects of Pretreatment with Tocovid on Oxidative Stress in Postischemic Mice Brain

Jingwei Shang, Hongjing Yan, Yang Jiao, Yasuyuki Ohta, Xia Liu, Xianghong Li, Ryuta Morihara, Yumiko Nakano, Yusuke Fukui, Xiaowen Shi, Yong Huang, Tian Feng, Mami Takemoto, Kota Sato, Nozomi Hishikawa, Toru Yamashita, Koji Abe

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

Background: Dietary supplement is an attempt to reduce the risk of ischemic stroke in high-risk population. A new mixed vitamin E-Tocovid that mainly contains tocotrienols other than tocopherol, attenuated the progression of white matter lesions by oral in humans. However, the effect of Tocovid on ischemic stroke has not been examined. In the present study, we assessed the therapeutic effects of Tocovid pretreatment on transient middle cerebral artery occlusion (tMCAO) in mice. Materials and Methods: After pretreatment with Tocovid (200 mg/kg/d) or vehicle for 1 month, 60-minute tMCAO was performed, and these mice were examined at 1 day, 3 days, and 7 days after reperfusion. We histologically assessed the effects of Tocovid pretreatment on the expressive changes of oxidative stress markers, cleaved caspase-3, and LC3-II after tMCAO in mice. Results: We observed that Tocovid pretreatment significantly improved the rotarod time, reduced infarct volume, decreased the number of 4-HNE, nitrotyrosine, and 8-OhdG positive cells, inhibited advanced glycation end products biomarkers RAGE, CMA, and CML expressions, and increased Nrf2 and MRP1 levels with GSSG/GSH ratio decrease. Furthermore, Tocovid pretreatment greatly decreased cleaved caspase-3 and LC3-II expressions after tMCAO. Conclusions: The present study obviously demonstrated that Tocovid pretreatment showed neuroprotective effects against oxidative stress and at least in part by antiapoptotic/autophagic cell death in ischemic mice brain.

Original languageEnglish
JournalJournal of Stroke and Cerebrovascular Diseases
DOIs
Publication statusAccepted/In press - Jan 1 2018

Fingerprint

Middle Cerebral Artery Infarction
Therapeutic Uses
Oxidative Stress
Brain
Caspase 3
Stroke
Tocotrienols
Advanced Glycosylation End Products
Tocopherols
Glutathione Disulfide
Autophagy
Neuroprotective Agents
Dietary Supplements
Vitamin E
Reperfusion
Biomarkers
Population

Keywords

  • Apoptosis
  • autophagic cell death
  • ischemic stroke
  • oxidative stress
  • Tocovid

ASJC Scopus subject areas

  • Surgery
  • Rehabilitation
  • Clinical Neurology
  • Cardiology and Cardiovascular Medicine

Cite this

Therapeutic Effects of Pretreatment with Tocovid on Oxidative Stress in Postischemic Mice Brain. / Shang, Jingwei; Yan, Hongjing; Jiao, Yang; Ohta, Yasuyuki; Liu, Xia; Li, Xianghong; Morihara, Ryuta; Nakano, Yumiko; Fukui, Yusuke; Shi, Xiaowen; Huang, Yong; Feng, Tian; Takemoto, Mami; Sato, Kota; Hishikawa, Nozomi; Yamashita, Toru; Abe, Koji.

In: Journal of Stroke and Cerebrovascular Diseases, 01.01.2018.

Research output: Contribution to journalArticle

Shang, Jingwei ; Yan, Hongjing ; Jiao, Yang ; Ohta, Yasuyuki ; Liu, Xia ; Li, Xianghong ; Morihara, Ryuta ; Nakano, Yumiko ; Fukui, Yusuke ; Shi, Xiaowen ; Huang, Yong ; Feng, Tian ; Takemoto, Mami ; Sato, Kota ; Hishikawa, Nozomi ; Yamashita, Toru ; Abe, Koji. / Therapeutic Effects of Pretreatment with Tocovid on Oxidative Stress in Postischemic Mice Brain. In: Journal of Stroke and Cerebrovascular Diseases. 2018.
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AU - Shang, Jingwei

AU - Yan, Hongjing

AU - Jiao, Yang

AU - Ohta, Yasuyuki

AU - Liu, Xia

AU - Li, Xianghong

AU - Morihara, Ryuta

AU - Nakano, Yumiko

AU - Fukui, Yusuke

AU - Shi, Xiaowen

AU - Huang, Yong

AU - Feng, Tian

AU - Takemoto, Mami

AU - Sato, Kota

AU - Hishikawa, Nozomi

AU - Yamashita, Toru

AU - Abe, Koji

PY - 2018/1/1

Y1 - 2018/1/1

N2 - Background: Dietary supplement is an attempt to reduce the risk of ischemic stroke in high-risk population. A new mixed vitamin E-Tocovid that mainly contains tocotrienols other than tocopherol, attenuated the progression of white matter lesions by oral in humans. However, the effect of Tocovid on ischemic stroke has not been examined. In the present study, we assessed the therapeutic effects of Tocovid pretreatment on transient middle cerebral artery occlusion (tMCAO) in mice. Materials and Methods: After pretreatment with Tocovid (200 mg/kg/d) or vehicle for 1 month, 60-minute tMCAO was performed, and these mice were examined at 1 day, 3 days, and 7 days after reperfusion. We histologically assessed the effects of Tocovid pretreatment on the expressive changes of oxidative stress markers, cleaved caspase-3, and LC3-II after tMCAO in mice. Results: We observed that Tocovid pretreatment significantly improved the rotarod time, reduced infarct volume, decreased the number of 4-HNE, nitrotyrosine, and 8-OhdG positive cells, inhibited advanced glycation end products biomarkers RAGE, CMA, and CML expressions, and increased Nrf2 and MRP1 levels with GSSG/GSH ratio decrease. Furthermore, Tocovid pretreatment greatly decreased cleaved caspase-3 and LC3-II expressions after tMCAO. Conclusions: The present study obviously demonstrated that Tocovid pretreatment showed neuroprotective effects against oxidative stress and at least in part by antiapoptotic/autophagic cell death in ischemic mice brain.

AB - Background: Dietary supplement is an attempt to reduce the risk of ischemic stroke in high-risk population. A new mixed vitamin E-Tocovid that mainly contains tocotrienols other than tocopherol, attenuated the progression of white matter lesions by oral in humans. However, the effect of Tocovid on ischemic stroke has not been examined. In the present study, we assessed the therapeutic effects of Tocovid pretreatment on transient middle cerebral artery occlusion (tMCAO) in mice. Materials and Methods: After pretreatment with Tocovid (200 mg/kg/d) or vehicle for 1 month, 60-minute tMCAO was performed, and these mice were examined at 1 day, 3 days, and 7 days after reperfusion. We histologically assessed the effects of Tocovid pretreatment on the expressive changes of oxidative stress markers, cleaved caspase-3, and LC3-II after tMCAO in mice. Results: We observed that Tocovid pretreatment significantly improved the rotarod time, reduced infarct volume, decreased the number of 4-HNE, nitrotyrosine, and 8-OhdG positive cells, inhibited advanced glycation end products biomarkers RAGE, CMA, and CML expressions, and increased Nrf2 and MRP1 levels with GSSG/GSH ratio decrease. Furthermore, Tocovid pretreatment greatly decreased cleaved caspase-3 and LC3-II expressions after tMCAO. Conclusions: The present study obviously demonstrated that Tocovid pretreatment showed neuroprotective effects against oxidative stress and at least in part by antiapoptotic/autophagic cell death in ischemic mice brain.

KW - Apoptosis

KW - autophagic cell death

KW - ischemic stroke

KW - oxidative stress

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