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Sulforaphane reduces apoptosis and oncosis along with protecting liver injury-induced ischemic reperfusion by activating the Nrf2/ARE pathway

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Abstract

Purpose

The purpose of this study was to determine the effect of sulforaphane (SFN) on hepatic ischemia reperfusion injury (HIRI) and to explore the underlying mechanisms.

Methods

The rat model of HIRI was established. Thirty-two rats were randomly divided into sham (A), SFN (B), HIRI (C), and SFN + HIRI (D) groups. Animals in the HIRI and Sham groups were treated with equal volumes of the vehicle of SPF. Liver functions were evaluated by serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST). Liver samples were collected for histological examination and determination of malondialdehyde (MDA), superoxide dismutase (SOD), glutathione (GSH), and glutathione peroxidase (GSH-Px) levels. Mitochondrial Na+–K+-ATPase and Ca2+-ATPase were measured by colorimetry. Expression levels of NQO1, Nrf2, and HO-1 in liver tissue were detected by western blot analysis. Additionally, oncosis and apoptosis were detected by Annexin V-FITC/PI immunofluorescent flow cytometry analysis.

Results

The HIRI group showed a significant increase in serum levels of liver enzymes (ALT, AST) associated with histopathological damage in the liver. Pre-treatment with SFN could reduce the levels of MDA and MPO in liver tissue and improve the activities of SOD, GSH, GSH-Px, and mitochondrial Na+–K+-ATPase and Ca2+-ATPase in liver tissue. Moreover, SFN could still increase the expression of NQO1, Nrf2, and HO-1 in liver tissue and decrease the oncosis and apoptosis of liver cells.

Conclusions

Pre-treatment with SFN could attenuate HIRI via the activation of Nrf2/ARE signaling pathways, ameliorate oxidative stress, and maintain the normal activities of Na+–K+-ATPase and Ca2+-ATPase, thus reducing the occurrence of cell oncosis and apoptosis. Therefore, SFN can be considered a potential candidate as an anti-ischemic medication to minimize HIRI.

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Acknowledgements

The study was supported by the Science and Technology Project Foundation of Guangdong Province, China (No. 2011B031800361).

Compliance with ethical requirements and Conflict of interest

Animal care and surgical procedures were approved by the Institutional Review Board of Sun Yat-sen University under the guidelines of the Chinese Academy of Sciences and carried out in accordance with the provisions of the NIH Guide for the Care and Use of Laboratory Animals. **n** Chi, Rui Zhang, Ning Shen, Yi **, Ayep Alina, Simin Yang and Shiqing Lin declare that they have no conflicts of interest.

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    Authors and Affiliations

    1. Department of Anesthesiology, Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510630, Guangdong, China

      **n** Chi & Ning Shen

    2. Department of General Surgery, The Third **angya Hospital of Central South University, Changsha, 410013, Hunan, China

      Rui Zhang

    3. Department of Pathology, Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510630, Guangdong, China

      Yi **

    4. Department of Anesthesiology, First Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510080, Guangdong, China

      Ayep Alina, Simin Yang & Shiqing Lin

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    Correspondence to Shiqing Lin.

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    **n** Chi and Rui Zhang contributed equally to this study.

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    Chi, X., Zhang, R., Shen, N. et al. Sulforaphane reduces apoptosis and oncosis along with protecting liver injury-induced ischemic reperfusion by activating the Nrf2/ARE pathway. Hepatol Int 9, 321–329 (2015). https://doi.org/10.1007/s12072-014-9604-y

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