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Oxysophoridine Protects Against Focal Cerebral Ischemic Injury by Inhibiting Oxidative Stress and Apoptosis in Mice

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Abstract

Our previous studies have demonstrated that oxysophoridine (OSR) has protective effects on cerebral neurons damage in vitro induced by oxygen and glucose deprivation. In this study, we further investigated whether OSR could reduce ischemic cerebral injury in vivo and its possible mechanism. Male Institute of cancer research mice were intraperitoneally injected with OSR (62.5, 125 and 250 mg/kg) for seven successive days, then subjected to brain ischemia induced by the model of middle cerebral artery occlusion. After reperfusion, neurological scores and infarct volume were estimated. Morphological examination of tissues was performed. Apoptotic neurons were detected by terminal deoxynucleotidyl transferase mediated dUTP nick end labeling staining. Oxidative stress levels were assessed by measurement of malondialdehyde (MDA), superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) levels. The expression of various apoptotic markers as Caspase-3, Bax and Bcl-2 were investigated by immunohistochemistry and Western-blot analysis. OSR pretreatment groups significantly reduced infract volume and neurological deficit scores. OSR decreased the percentage of apoptotic neurons, relieved neuronal morphological damage. Moreover, OSR markedly decreased MDA content, and increased SOD, GSH-Px activities. Administration of OSR (250 mg/kg) significantly suppressed overexpression of Caspase-3 and Bax, and increased Bcl-2 expression. These findings indicate that OSR has a protective effect on focal cerebral ischemic injury through antioxidant and anti-apoptotic mechanisms.

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Abbreviations

ECA:

External carotid artery

ECL:

Enhanced chemiluminescence

GSH-Px:

Glutathione peroxidase

HE:

Hematoxylin-eosin staining

ICA:

Internal carotid artery

ICR:

Institute of cancer research

MCA:

Middle cerebral artery

MCAO:

Middle cerebral artery occlusion

MDA:

Malondialdehyde

OSR:

Oxysophoridine

PVDF:

Transferred onto a polyvinylidene difluoride

SDS-PAGE:

Sodium dodecyl sulfate-polyacrylamide gel electrophoresis

SOD:

Superoxide dismutase

TTC:

2,3,5-Triphenyl tetrazolium chloride

TUNEL:

Terminal deoxynucleotidyl transferase mediated dUTP nick end labeling

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Acknowledgments

The authors gratefully acknowledge the financial supported by the National Natural Science Foundation of China (Grant No. 309605060, 81160524, 81360649), the Natural Science Foundation of Ningxia (Grant No. NZ11212) and Ningxia Hui Autonomous Region, colleges and universities of science and technology research projects (NGY2012055). We are indebted to the staff in the animal center and the Science & Technology Centre who provided assistance in the study.

Conflict of interest

The authors declare that they have no competing interests.

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Authors and Affiliations

  1. Department of Pharmacology, Ningxia Medical University, 1160 Shengli Street, Yinchuan, 750004, Ningxia, People’s Republic of China

    Teng-Fei Wang, Zhen Lei, Yong-Sheng Wang, Yin-Ju Hao, Ru Zhou, Shao-Ju Jin, Juan Du, Juan Li & Jian-Qiang Yu

  2. Shanghai Pudong New Area Gongli Hospital, No.219, Miaopu Road, Shanghai, 200135, People’s Republic of China

    Yu-Xiang Li & Jian-Qiang Yu

  3. Technology Centre, Ningxia Medical University, Yinchuan, 750004, People’s Republic of China

    Jie Wang & Shu-Jing Wang

  4. Ningxia Key Lab of Craniocerebral Diseases of Ningxia Hui Autonomous Region, Ningxia Medical University, Yinchuan, 750004, People’s Republic of China

    Tao Sun

Authors
  1. Teng-Fei Wang
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  2. Zhen Lei
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  10. Juan Du
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  11. Juan Li
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  12. Tao Sun
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  13. Jian-Qiang Yu
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Corresponding author

Correspondence to Jian-Qiang Yu.

Additional information

Teng-Fei Wang, Zhen Lei and Yu-Xiang Li have contributed equally to this study.

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Wang, TF., Lei, Z., Li, YX. et al. Oxysophoridine Protects Against Focal Cerebral Ischemic Injury by Inhibiting Oxidative Stress and Apoptosis in Mice. Neurochem Res 38, 2408–2417 (2013). https://doi.org/10.1007/s11064-013-1153-6

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  • DOI: https://doi.org/10.1007/s11064-013-1153-6

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