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Neuroprotective Effects of Kukoamine a against Radiation-induced Rat Brain Injury through Inhibition of Oxidative Stress and Neuronal Apoptosis

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Abstract

Radiation-induced brain injury (RIBI) is a prominent side effect of radiotherapy for cranial tumors. Kukoamine A (KuA) has the ability of anti-oxidative stress and anti-apoptosis in vitro. The aim of this study was to investigate whether KuA would prevent the detrimental effect of ionizing radiation on hippocampal neurons. For this study, male Wistar rats were received either sham irradiation or whole brain irradiation (30 Gy single dose of X-rays) followed by the immediate injection of either KuA or vehicle intravenously. The dose of KuA was 5, 10 and 20 mg/kg respectively. The protective effects of KuA were assessed by Nissl staining. The levels of oxidative stress marker and antioxidants activities were assayed by kits. TUNEL staining was performed to detect the level of apoptosis in hippocampal neurons. The expression of apoptosis-related proteins as well as the brain-derived neurophic factor (BDNF) was evaluated by western blot. Whole brain irradiation led to the neuronal abnormality and it was alleviated by KuA. KuA decreased malondialdehyde (MDA) level, increased glutathione (GSH) level, superoxide dismutase (SOD) and catalase (CAT) activities, as well as alleviated neuronal apoptosis by regulating the expression of cleaved caspase-3, cytochrome C, Bax and Bcl-2. Additionally, KuA increased the expression of BDNF. These data indicate that KuA has neuroprotective effects against RIBI through inhibiting neuronal oxidative stress and apoptosis.

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Acknowledgments

This work was supported by the National Science and Technology Major Project, People’s republic of China (Project Number: 2014ZX09J14101-05C).

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Authors and Affiliations

  1. School of Life Sciences and Biopharmaceutis, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang, Liaoning, 110016, China

    Yaqiong Zhang & Qingchun Zhao

  2. Department of Pharmacy, General Hospital of Shenyang Military Area Command, Shenyang, 83 Wenhua Road, Shenyang, Liaoning, 110016, China

    Changli Wang, Hongda Ma, Weihong Meng & Qingchun Zhao

  3. Department of Radiation Oncology, General Hospital of Shenyang Military Area Command, 83 Wenhua Road, Shenyang, Liaoning, 110016, China

    Zhihua Cheng

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  1. Yaqiong Zhang
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Correspondence to Qingchun Zhao.

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Zhang, Y., Cheng, Z., Wang, C. et al. Neuroprotective Effects of Kukoamine a against Radiation-induced Rat Brain Injury through Inhibition of Oxidative Stress and Neuronal Apoptosis. Neurochem Res 41, 2549–2558 (2016). https://doi.org/10.1007/s11064-016-1967-0

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  • DOI: https://doi.org/10.1007/s11064-016-1967-0

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