Skip to main content
SpringerLink
Log in

Effect of 3,3′-diselenodipropionic Acid on Dextran Sodium Sulfate–Induced Ulcerative Colitis in Mice

  • Published:
Biological Trace Element Research Aims and scope Submit manuscript

Abstract

3,3′-Diselenodipropionic acid (DSePA), a synthetic organoselenium compound, has received considerable attention because of its antioxidant properties and safety. Its protective effect against dextran sodium sulfate (DSS)–induced mouse ulcerative colitis (UC) and the role of T helper 17 (Th17) cell proliferation were investigated. Fifty C57BL/6 male mice were randomly assigned to one of five groups: control (Con), DSePA, DSS, low-dose DSePA (LSe), and high-dose DSePA (HSe). Mice in the DSS, LSe, and HSe groups drank 2% DSS to induce UC, and received normal saline, 1 and 2 mg/mL DSePA solution by intraperitoneal injection, respectively. The DSePA group only received 2 mg/mL DSePA solution. After 5 weeks, DSS challenge induced UC in the mice, which manifested as decreased body weight, shortened colon length, the loss of goblet cells, activated proliferating cells, and multiple signs of intestinal lesions by histological observation, all of which were reversed to varying degrees by DSePA administration. DSS upregulated the colonic protein expression of the macrophage marker F4/80 and proinflammatory cytokines (IL-1β, IL-6, and TNFα), whereas DSePA administration downregulated the expression of these factors. DSS upregulated the mRNA expression of retinoic acid receptor–related orphan receptor γt (RORγt, mainly expressed in Th17 cells), IL-17A, and IL-17F and the levels of IL-17A and IL-17F in the colon, whereas DSePA administration decreased them. No difference was observed between the Con group and the DSePA group without DSS induction. Thus, DSePA administration ameliorated DSS-induced UC by regulating Th17-cell proliferation and the secretion of proinflammatory cytokines.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6

Similar content being viewed by others

Data Availability

The datasets used or analyzed during the current study are available from the corresponding author on reasonable request.

References

  1. Podolsky DK (2002) Inflammatory bowel disease. N Engl J Med 347:417–429. https://doi.org/10.1056/NEJMra020831

    Article  CAS  PubMed  Google Scholar 

  2. Sang LX, Chang B, Zhu JF, Yang FL, Li Y, Jiang XF, Wang DN, Lu CL, Sun X (2017) Sodium selenite ameliorates dextran sulfate sodium-induced chronic colitis in mice by decreasing Th1, Th17, and γδT and increasing CD4(+) CD25(+) regulatory T-cell responses. World J Gastroenterol 23:3850–3863. https://doi.org/10.3748/wjg.v23.i21.3850

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Han L, Yang J, Wang X, Li D, Lv L, Li B (2014) Th17 cells in autoimmune diseases. Front Med 9:10–19. https://doi.org/10.1007/s11684-015-0388-9

    Article  Google Scholar 

  4. Zhang M, Zhou L, Xu Y, Yang M, Xu Y, Komaniecki GP, Kosciuk T, Chen X, Lu X, Zou X, Linder ME, Lin H (2020) A STAT3 palmitoylation cycle promotes TH 17 differentiation and colitis. Nature 586:434–439. https://doi.org/10.1038/s41586-020-2799-2

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Kunwar A, Priyadarsini KI, Jain VK (2020) 3,3′-Diselenodipropionic acid (DSePA): a redox active multifunctional molecule of biological relevance. Biochim Biophys Acta Gen Subj 1865:129768. https://doi.org/10.1016/j.bbagen.2020.129768

    Article  CAS  PubMed  Google Scholar 

  6. Shi C, Yue F, Shi F, Qin Q, Wang L, Wang G, Mu L, Liu D, Li Y, Yu T, She J (2021) Selenium-containing amino acids protect dextran sulfate sodium-induced colitis via ameliorating oxidative stress and intestinal inflammation. J Inflam Res 14:85–95. https://doi.org/10.2147/JIR.S288412

    Article  Google Scholar 

  7. Kunwar A, Bag PP, Chattopadhyay S, Jain VK, Priyadarsini KI (2011) Anti-apoptotic, anti-inflammatory, and immunomodulatory activities of 3,3′-diselenodipropionic acid in mice exposed to whole body γ-radiation. Arch Toxicol 85:1395–1405. https://doi.org/10.1007/s00204-011-0687-0

    Article  CAS  PubMed  Google Scholar 

  8. Gandhi VV, Gandhi KA, Kumbhare LB, Goda JS, Gota V, Priyadarsini KI, Kunwar A (2021) 3,3′-Diselenodipropionic acid (DSePA) induces reductive stress in A549 cells triggering p53-independent apoptosis a novel mechanism for diselenides. Free Radic Biol Med 175:1–17. https://doi.org/10.1016/j.freeradbiomed.2021.08.017

    Article  CAS  PubMed  Google Scholar 

  9. Kunwar A, Bansal P, Kumar SJ, Bag PP, Paul P, Reddy ND, Kumbhare LB, Jain VK, Chaubey RC, Unnikrishnan MK, Priyadarsini KI (2010) In vivo radioprotection studies of 3,3′-diselenodipropionic acid, a selenocystine derivative. Free Radic Biol Med 48:399–410. https://doi.org/10.1016/j.freeradbiomed.2009.11.009

    Article  CAS  PubMed  Google Scholar 

  10. Gandhi KA, Goda JS, Gandhi VV, Sadanpurwala A, Jain VK, Joshi K, Epari S, Rane S, Mohanty B, Chaudhari P, Kembhavi S, Kunwar A, Gota V, Priyadarsini KI (2019) Oral administration of 3,3′-diselenodipropionic acid prevents thoracic radiation induced pneumonitis in mice by suppressing NF-kB/IL-17/G-CSF/neutrophil axis. Free Radic Biol Med 145:8–19. https://doi.org/10.1016/j.freeradbiomed.2019.09.009

    Article  CAS  PubMed  Google Scholar 

  11. Perše M, Cerar A (2012) Dextran sodium sulphate colitis mouse model: traps and tricks. J Biomed Biotechnol 2012:718617. https://doi.org/10.1155/2012/718617

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Kobayashi K, Ashina K, Derouiche S, Hamabata T, Nakamura T, Nagata N, Takenouchi S, Tominaga M, Murata T (2021) 5,6-dihydroxy-8Z,11Z,14Z,17Z-eicosatetraenoic acid accelerates the healing of colitis by inhibiting transient receptor potential vanilloid 4-mediated signaling. FASEB J 35:e21238. https://doi.org/10.1096/fj.201903207RRR

    Article  CAS  PubMed  Google Scholar 

  13. Zhong Y, Jin Y, Zhang Q, Mao B, Tang X, Huang J, Guo R, Zhao J, Cui S, Chen W (2022) Comparison of selenium-enriched Lactobacillus paracasei, selenium-enriched yeast, and selenite for the alleviation of DSS-induced colitis in mice. Nutrients 14:2433. https://doi.org/10.3390/nu14122433

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Chen H, Du G, Yan X, Ye H, Guo Q, Wang Z, Yuan Y, Yue T (2022) Selenium-enriched Pediococcus acidilactici MRS-7 alleviates patulin-induced jejunum injuries in mice and its possible mechanisms. J Agric Food Chem 70:4755–4764

    Article  CAS  PubMed  Google Scholar 

  15. Andrés-Sánchez N, Fisher D, Krasinska L (2022) Physiological functions and roles in cancer of the proliferation marker Ki-67. J Cell Sci 135: jcs258932. https://doi.org/10.1242/jcs.258932.

  16. Hirsch S, Gordon S (1982) The use and limitation of monoclonal antibodies against mononuclear phagocytes. Immunobiology 161:298–307. https://doi.org/10.1016/S0171-2985(82)80086-7

    Article  CAS  PubMed  Google Scholar 

  17. Camporeale A, Poli V (2012) IL-6, IL-17 and STAT3: a holy trinity in auto-immunity? Front Biosci (Landmark Ed) 17:2306–2326. https://doi.org/10.2741/4054

    Article  CAS  PubMed  Google Scholar 

  18. Zúñiga LA, Jain R, Haines C, Cua DJ (2013) Th17 cell development: from the cradle to the grave. Immunol Rev 252:78–88. https://doi.org/10.1111/imr.12036

    Article  CAS  PubMed  Google Scholar 

  19. Zhao Y, Chen H, Li W, He Q, Liang J, Yan X, Yuan Y, Yue T (2022) Selenium-containing tea polysaccharides ameliorate DSS-induced ulcerative colitis via enhancing the intestinal barrier and regulating the gut microbiota. Int J Biol Macromol 209(Pt A):356–366. https://doi.org/10.1016/j.ijbiomac.2022.04.028.

  20. Britton GJ, Contijoch EJ, Mogno I, Vennaro OH, Llewellyn SR, Ng R, Li Z, Mortha A, Merad M, Das A, Gevers D, McGovern DPB, Singh N, Braun J, Jacobs JP, Clemente JC, Grinspan A, Sands BE, Colombel JF, Dubinsky MC, Faith JJ (2019) Microbiotas from humans with inflammatory bowel disease alter the balance of gut Th17 and RORγt + regulatory T cells and exacerbate colitis in mice. Immunity 50:212-224.e4. https://doi.org/10.1016/j.immuni.2018.12.015

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Strober W, Fuss IJ (2011) Proinflammatory cytokines in the pathogenesis of inflammatory bowel diseases. Gastroenterology 140:1756–1767. https://doi.org/10.1053/j.gastro.2011.02.016

    Article  CAS  PubMed  Google Scholar 

  22. Zhu C, Ling Q, Cai Z, Wang Y, Zhang Y, Hoffmann PR, Zheng W, Zhou T, Huang Z (2016) Selenium-containing phycocyanin from Se-enriched Spirulina platensis reduces inflammation in dextran sulfate sodium-induced colitis by inhibiting NF-κB activation. J Agric Food Chem 64:5060–5070. https://doi.org/10.1021/acs.jafc.6b01308

    Article  CAS  PubMed  Google Scholar 

  23. Kassab RB, Elbaz M, Oyouni AAA, Mufti AH, Theyab A, Al-Brakati A, Mohamed HA, Hebishy AMS, Elmallah MIY, Abdelfattah MS, Abdel Moneim AE (2022) Anticolitic activity of prodigiosin loaded with selenium nanoparticles on acetic acid–induced colitis in rats. Environ Sci Pollut Res Int 29:55790–55802. https://doi.org/10.1007/s11356-022-19747-1

    Article  CAS  PubMed  Google Scholar 

  24. Cai J, Liu J, Fan P, Dong X, Zhu K, Liu X, Zhang N, Cao Y (2021) Dioscin prevents DSS-induced colitis in mice with enhancing intestinal barrier function and reducing colon inflammation. Int Immunopharmacol 99:108015. https://doi.org/10.1016/j.intimp.2021.108015

    Article  CAS  PubMed  Google Scholar 

  25. Zhang H, Wang J, Lang W, Liu H, Zhang Z, Wu T, Li H, Bai L, Shi Q (2022) Albiflorin ameliorates inflammation and oxidative stress by regulating the NF-κB/NLRP3 pathway in Methotrexate-induced enteritis. Int Immunopharmacol 109:108824. https://doi.org/10.1016/j.intimp.2022.108824

    Article  CAS  PubMed  Google Scholar 

  26. Xavier RJ, Podolsky DK (2007) Unravelling the pathogenesis of inflammatory bowel disease. Nature 448(7152):427–434. https://doi.org/10.1038/nature06005

    Article  CAS  PubMed  Google Scholar 

  27. Ivanov II, McKenzie BS, Zhou L, Tadokoro CE, Lepelley A, Lafaille JJ, Cua DJ, Littman DR (2006) The orphan nuclear receptor RORgammat directs the differentiation program of proinflammatory IL-17+ T helper cells. Cell 126:1121–1133. https://doi.org/10.1016/j.cell.2006.07.035

    Article  CAS  PubMed  Google Scholar 

  28. Katz Y, Nadiv O, Beer Y (2001) Interleukin-17 enhances tumor necrosis factor alpha-induced synthesis of interleukins 1, 6, and 8 in skin and synovial fibroblasts: a possible role as a “fine-tuning cytokine” in inflammation processes. Arthritis Rheum 44:2176–2184. https://doi.org/10.1002/1529-0131(200109)44:9%3c2176:aid-art371%3e3.0.co;2-4

    Article  CAS  PubMed  Google Scholar 

  29. Fujino S, Andoh A, Bamba S, Ogawa A, Hata K, Araki Y, Bamba T, Fujiyama Y (2003) Increased expression of interleukin 17 in inflammatory bowel disease. Gut 52:65–70. https://doi.org/10.1136/gut.52.1.65

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Wu Z, Pan D, Jiang M, Sang L, Chang B (2021) Selenium-enriched Lactobacillus acidophilus ameliorates dextran sulfate sodium-induced chronic colitis in mice by regulating inflammatory cytokines and intestinal microbiota. Front Med (Lausanne) 8:716816. https://doi.org/10.3389/fmed.2021.716816

    Article  PubMed  Google Scholar 

  31. Johnson DE, O’Keefe RA, Grandis JR (2018) Targeting the IL-6/JAK/STAT3 signalling axis in cancer. Nat Rev Clin Oncol 15:234–248. https://doi.org/10.1038/nrclinonc.2018.8

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Camporeale A, Poli V (2012) IL-6, IL-17 and STAT3: a holy trinity in auto-immunity? Front Biosci (Landmark Ed) 17:2306–2326. https://doi.org/10.2741/4054

    Article  CAS  PubMed  Google Scholar 

  33. Suzuki A, Hanada T, Mitsuyama K, Yoshida T, Kamizono S, Hoshino T, Kubo M, Yamashita A, Okabe M, Takeda K, Akira S, Matsumoto S, Toyonaga A, Sata M, Yoshimura A (2001) CIS3/SOCS3/SSI3 plays a negative regulatory role in STAT3 activation and intestinal inflammation. J Exp Med 193(4):471–481. https://doi.org/10.1084/jem.193.4.471

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Zhou L, Zhang M, Wang Y, Dorfman RG, Liu H, Yu T, Chen X, Tang D, Xu L, Yin Y, Pan Y, Zhou Q, Zhou Y, Yu C (2018) Faecalibacterium prausnitzii produces butyrate to maintain Th17/Treg balance and to ameliorate colorectal colitis by inhibiting histone deacetylase 1. Inflamm Bowel Dis 24:1926–1940. https://doi.org/10.1093/ibd/izy182

    Article  PubMed  Google Scholar 

Download references

Funding

This work was supported by the Research on the Safe Range of Dietary Selenium Intake (International Cooperation) (D20180031), and the Special Fund for Functional Agricultural Development of Nanjing National Agricultural Innovation Park (NJGJNCY-FAST01).

Author information

Author notes

  1. Jia-Yang Zheng and Jia-Ying Xu contributed equally to this work.

Authors and Affiliations

  1. Department of Nutrition and Food Hygiene, School of Public Health, Soochow University, 199 Ren’ai Road, Suzhou, 215123, China

    Jia-Yang Zheng, Lin Zhang & Li-Qiang Qin

  2. State Key Laboratory of Radiation Medicine and Protection, School of Radiation Medicine and Protection, Soochow University, Suzhou, China

    Jia-Ying Xu

  3. Advanced Lab for Functional Agriculture, Suzhou Institute for Advanced Research, University of Science and Technology of China, Suzhou, China

    Zhang-Min Wang & Xue-Bin Yin

  4. Nanjing Institute for Functional Agriculture Science and Technology (iFAST), Nanjing, China

    Zhang-Min Wang & Xue-Bin Yin

Authors
  1. Jia-Yang Zheng
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Jia-Ying Xu
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Lin Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Zhang-Min Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Xue-Bin Yin
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Li-Qiang Qin
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

Jia-Ying Xu, Li-Qiang Qin, and Xue-Bin Yin designed the experiments; Jia-Yang Zheng and Lin Zhang performed this animal study; Jia-Yang Zheng and Zhang-Min Wang analyzed the data; Jia-Yang Zheng and Li Qiang Qin prepared the paper; Jia-Ying Xu, Xue-Bin Yin, and Li-Qiang Qin supervised the research. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Li-Qiang Qin.

Ethics declarations

Ethics Approval

All the experiments were carried out in accordance with the Guidelines for the Care of Animals, and all experimental procedures were approved by Soochow University Animal Welfare Committee (202103A353).

Competing Interests

The authors declare no competing interests.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Zheng, JY., Xu, JY., Zhang, L. et al. Effect of 3,3′-diselenodipropionic Acid on Dextran Sodium Sulfate–Induced Ulcerative Colitis in Mice. Biol Trace Elem Res 201, 3961–3970 (2023). https://doi.org/10.1007/s12011-022-03491-1

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12011-022-03491-1

Keywords

Search

Navigation