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Selenomethionine Alleviates Intestinal Ischemia–Reperfusion Injury in Mice Through the Bax-Caspase Pathway

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Abstract

Selenomethionine (SeMet) is known to alleviate ischemia–reperfusion (I/R) injury. However, its details of action have not been thoroughly elucidated in mice with intestinal I/R injury. In this study, intestinal I/R injury mice models were established, and ELISAs were performed to determine the levels of redox factors, including glutathione peroxidase (GSH-Px), catalase (CAT), superoxide dismutase (SOD), and malondialdehyde (MDA), in mice intestinal tissues. Furthermore, several apoptosis-related markers, such as cytochrome c (Cyt-c), Bcl-2, and Bax, were detected using qPCR and Western blotting, while caspase-3 was detected using Western blotting alone. The results showed that SeMet alleviated I/R damage by increasing GSH-Px, CAT, and SOD levels and reducing MDA levels. Our data demonstrated that SeMet reduced I/R injury and inhibited the expression of Cyt-c, Bax, and caspase-3. SeMet also increased the expression of Bcl-2 in the intestinal tissues of mice. In addition, the TUNEL assay results showed that SeMet mitigated apoptosis in the villi cells of the intestinal mucosa. The findings also revealed that I/R could lead to increased apoptosis levels and that SeMet alleviated I/R-induced apoptosis by mediating the Bax/cytochrome C/caspase-3 apoptotic signaling pathways in the intestinal I/R injury mice models. Thus, SeMet inhibited apoptosis and resulted in an increase of Bcl-2 levels; downregulated the expression of Bax, Cyt-c, and caspase-3; and alleviated the intestinal ischemia injury in mice. The I/R injury increased the cytosolic Bax, Cyt-c, and caspase-3 levels and significantly decreased Bcl-2 expression levels in the I/R group, compared to the Sham group. However, the levels of all markers were reversed post-SeMet pre-treatment.

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Data Availability

Data has been shared in the submitted article. Some data supporting the findings of this study will be availed upon request from the corresponding author. Some data are, however, are not publicly available due to privacy or ethical restrictions.

References

  1. Liu Z, Zhang F, Cui L, Wang J, Ping Lu, Zhao R, Zhang H, Wang J, Li C, Rui Wu (2020) Quantitative proteomic analysis reveals that the Rap1/MAPK/ERK pathway is inhibited through selenomethionine strengthening antioxidant activity. Biometals 33:45–64

    Article  CAS  Google Scholar 

  2. Wan XL, Ju GY, Xu L, Yang HM, Wang ZY (2019) Dietary selenomethionine increases antioxidant capacity of geese by improving glutathione and thioredoxin systems. Poult Sci 1; 98(9): 3763–3769.

  3. Wan X, Ju G, Xu L, Yang H, Wang Z (2020) Selenomethionine improves antioxidant capacity of breast muscle in geese via stimulating glutathione system and thiol pool. Biol Trace Elem Res 198(1):253–259

    Article  CAS  Google Scholar 

  4. Yongsoo Kim, Dong Chil Kim, Eui-Sic Cho, Seung-O Ko, Woon Yong Kwon, Gil Joon Suh, Hyo-Keun Shin (2014) Antioxidant and anti-inflammatory effects of selenium in oral buccal mucosa and small intestinal mucosa during intestinal ischemia-reperfusion injury. J Inflamm (Lond) 30; 11(1): 36.

  5. Hsu CC, Huang CC, Chien LH, Lin MT, Chang CP, Lin HJ, Chio CC (2020) Ischemia/reperfusion injured intestinal epithelial cells cause cortical neuron death by releasing exosomal microRNAs associated with apoptosis, necroptosis, and pyroptosis. Sci Rep 1; 10(1): 14409.

  6. Jia Z, Lian W, Shi H, Cao C, Han S, Wang K, Li M, Zhang X (2017) Ischemic postconditioning protects against intestinal ischemia/reperfusion injury via the HIF-1α/miR-21 axis. Sci Rep 23 7(1): 16190.

  7. Takeda M, Miyahara K, Okawada M, Akazawa C, Lane GJ, Yamataka A (2017) Semaphorin 3A expression following intestinal ischemia/reperfusion injury in Sox10-Venus mice. Pediatr Surg Int 33(3):383–388

    Article  Google Scholar 

  8. Wang Z, Sun R, Wang G, Chen Z, Li Y, Zhao Y, Liu D, Zhao H, Zhang F, Yao J, Tian X (2020) SIRT3-mediated deacetylation of PRDX3 alleviates mitochondrial oxidative damage and apoptosis induced by intestinal ischemia/reperfusion injury. Redox Biol 28: 101343.

  9. Yamaguchi R, Lartigue L, Perkins G (2019) Targeting Mcl-1 and other Bcl-2 family member proteins in cancer therapy. Pharmacol Ther 195:13–20

    Article  CAS  Google Scholar 

  10. Ostadalova I, Vobecky M, Chvojkova Z, Mikova D, Hampl V, Wilhelm J, Ostadal B (2007) Selenium protects the immature rat heart against ischemia/reperfusion injury. Mol Cell Biochem 300:259–267

    Article  CAS  Google Scholar 

  11. Reyes L, Bishop DP, Hawkins CL, Rayner BS (2019) Assessing the efficacy of dietary selenomethionine supplementation in the setting of cardiac ischemia/reperfusion injury. Antioxidants (Basel) 3; 8(11): 546.

  12. Liu Z, Zhang F, Lu P, Zhao R, Zhang H, Song B, Li L, Wu Z, Wu R (2019) Selenium-yeast alleviated inflammatory damage caused by lead via inhibiting Ras/ERK pathway and inflammatory factors in chicken intestinal mucosas. Biol Trace Elem Res 190(2):493–500

    Article  CAS  Google Scholar 

  13. Gong ZG, Wang XY, Wang JH, Fan RF, Wang L (2019) Trehalose prevents cadmium-induced hepatotoxicity by blocking Nrf2 pathway, restoring autophagy and inhibiting apoptosis. J Inorg Biochem 192:62–71

    Article  CAS  Google Scholar 

  14. Kieliszek M, Błażejak S, Bzducha-Wróbel A (2015) Influence of selenium content in the culture medium on protein profile of yeast cells Candida utilis ATCC 9950. Oxid Med Cell Longev 659750.

  15. Chadani H, Usui S, Inoue O, Kusayama T, Takashima SI, Kato T, Murai H, Furusho H, Nomura A, Misu H, Takamura T, Kaneko S, Takamura M (2018) Endogenous selenoprotein P, a liver-derived secretory protein, mediates myocardial ischemia/reperfusion injury in mice. Int J Mol Sci 16; 19(3): 878.

  16. Oztürk C, Avlan D, Cinel I, Cinel L, Unlü A, Camdeviren H, Atik U, Oral U (2002) Selenium pre-treatment prevents bacterial translocation in rat intestinal ischemia/reperfusion model. Pharmacol Res 46:171–175

    Article  Google Scholar 

  17. Liu R, Jia T, Cui Y, Lin H, Li S (2018) The protective effect of selenium on the chicken pancreas against cadmium toxicity via alleviating oxidative stress and autophagy. Biol Trace Elem Res 184(1):240–246

    Article  CAS  Google Scholar 

  18. Fan RF, Cao CY, Chen MH, Shi QX, Xu SW (2018) Gga-let-7f-3p promotes apoptosis in selenium deficiency-induced skeletal muscle by targeting selenoprotein K. Metallomics 18; 10(7): 941–952.

  19. Hasanvand A, Abbaszadeh A, Darabi S, Nazari A, Gholami M, Kharazmkia A (2016) Evaluation of selenium on kidney function following ischemic injury in rats; protective effects and antioxidant activity. J Renal Inj Prev 24; 6 (2): 93–98.

  20. Zendedel A, Gharibi Z, Anbari K, Abbaszadeh A, Khayat ZK, Khorramabadi RM, Soleymaninejad M, Gholami M (2017) Selenium ameliorate peripheral nerve ischemic-reperfusion injury via decreased TNF-α. Biol Trace Elem Res 176(2):328–337

    Article  CAS  Google Scholar 

  21. Yang Y, Yang M, Ai F, Huang C (2017) Cardioprotective effect of Aloe vera biomacromolecules conjugated with selenium trace element on myocardial ischemia-reperfusion injury in rats. Biol Trace Elem Res 177(2):345–352

    Article  CAS  Google Scholar 

  22. Almoiliqy M, Wen J, Xu B, Sun YC, Lian MQ, Li YL, Qaed E, Al-Azab M, Chen DP, Shopit A, Wang L, Sun PY, Lin Y (2020) Cinnamaldehyde protects against rat intestinal ischemia/reperfusion injuries by synergistic inhibition of NF-κB and p53. Acta Pharmacol Sin 41(9):1208–1222

    Article  CAS  Google Scholar 

  23. Yazici A, Aksit H, Sari ES, Yay A, Erken HA, Aksit D, Cakmak H, Seyrek K, Ermis SS (2015) Comparison of pre-treatment and post-treatment use of selenium in retinal ischemia reperfusion injury. Int J Ophthalmol 18; 8(2): 263–8.

  24. Wang J, Liu Z, He X, Lian S, Liang J, Yu D, Sun D, Wu R (2018) Selenium deficiency induces duodenal villi cell apoptosis via an oxidative stress-induced mitochondrial apoptosis pathway and an inflammatory signaling-induced death receptor pathway. Metallomics 17; 10 (10): 1390–1400.

  25. Li Z, Guo D, Yin X, Ding S, Shen M, Zhang R, Wang Y, Xu R (2020) Zinc oxide nanoparticles induce human multiple myeloma cell death via reactive oxygen species and Cyt-C/Apaf-1/Caspase-9/Caspase-3 signaling pathway in vitro. Biomed Pharmacother. 122: 109712.

  26. Song XB, Liu G, Wang ZY, Wang L (2016) Puerarin protects against cadmium-induced proximal tubular cell apoptosis by restoring mitochondrial function. Chem Biol Interact 25(260):219–231

    Article  Google Scholar 

  27. Sun JY, Hou YJ, Fu XY, Fu XT, Ma JK, Yang MF, Sun BL, Fan CD, Oh J (2019) Selenium-containing protein from selenium-enriched Spirulina platensis attenuates cisplatin-induced apoptosis in MC3T3-E1 mouse preosteoblast by inhibiting mitochondrial dysfunction and ROS-mediated oxidative damage. Front Physiol 9(9):1907

    Article  Google Scholar 

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Acknowledgements

The authors wish to thank the study participants and Jilin University for their contributions to this study.

Funding

This work was supported by grants from the National key research and development program (2016YFD0501203), Foundation of National Natural Science Project, P.R. China (31472249;31772789), Foundation Project of Heilongjiang province natural (No. H2017038), Heilongjiang Bayi Agricultural University Support Program for “San Zong” (TDJH201905), and Heilongjiang Bayi Agricultural University Support Program of “San Heng San Zong” (ZRCPY201909).

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The authors have read and approved the final manuscript. Zhe Liu and Guangze Mou conceptualized the manuscript. Guangze Mou and Rui Zhao conducted the statistical analyses. Zhe Liu and Zhiming Liang generated Figs. 2 and 6. Guangze Mou generated Fig. 5. Zhiming Liang provided data and developed Table 1. Chenghao Jin revised the paper and generated Fig. 3. Rui Wu developed Figs. 1 and 4.

Corresponding authors

Correspondence to Chenghao Jin or Rui Wu.

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Animal Ethics statement: All experimental procedures were approved by the Management Committee of the Experimental Animal Center of Heilongjiang Bayi Agricultural University (License No.22–05-01). The authors agreed to participate.

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All authors have reviewed and approved the publication of the final version of the manuscript.

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The contribution of Zhe Liu and GuangZe Mou co-together is equally important in this article.

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Liu, Z., Mou, G., Liang, Z. et al. Selenomethionine Alleviates Intestinal Ischemia–Reperfusion Injury in Mice Through the Bax-Caspase Pathway. Biol Trace Elem Res 200, 3205–3214 (2022). https://doi.org/10.1007/s12011-021-02925-6

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