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Sulfasalazine and Chromotrope 2B reduce oxidative stress in murine bone marrow-derived mesenchymal stem cells

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Abstract

Background

With advancing age of stem cells, dysregulation of various processes at the cellular level occurs, thereby decreasing their regeneration potential. One of the changes that occurs during the aging process is the accumulation of reactive oxygen species (ROS), which accelerates the processes of cellular senescence and cell death. The aim of this study is to evaluate two antioxidant compounds; Chromotrope 2B and Sulfasalazine, for their antioxidant effects on young and old rat bone marrow mesenchymal stem cells (MSCs).

Methods and results

Oxidative stress was induced in MSCs by 5 µM dexamethasone for 96 h and the cells were treated with Chromotrope 2B or Sulfasalazine, 50 µM each. The effects of antioxidant treatment following oxidative stress induction was evaluated by transcriptional profiling of genes involved in the oxidative stress and telomere maintenance. Expression levels of Cat, Gpx7, Sod1, Dhcr24, Idh1, and Txnrd2 were found to be increased in young MSCs (yMSCs) as a result of oxidative stress, while Duox2, Parp1, and Tert1 expression were found to be decreased as compared to the control. In old MSCs (oMSCs), the expressions of Dhcr24, Txnrd2, and Parp1 increased, while that of Duox2, Gpx7, Idh1, and Sod1 decreased following oxidative stress. In both MSC groups, Chromotrope 2B prompted decrease in the ROS generation before and after the induction of oxidative stress. In oMSCs, ROS content was significantly reduced in the Sulfasalazine treated group.

Conclusion

Our findings suggest that both Chromotrope 2B and Sulfasalazine possess the potential to reduce the ROS content in both age groups, though the latter was found to be more potent. These compounds can be used to precondition MSCs to enhance their regenerative potential for future cell-based therapeutics.

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References

  1. Giri S, Machens HG, Bader A (2019) Therapeutic potential of endogenous stem cells and cellular factors for scar-free skin regeneration. Drug Discov Today 24(1):69–84

    Article  CAS  PubMed  Google Scholar 

  2. Caplan AI (2007) Adult mesenchymal stem cells for tissue Engineering Versus Regenerative Medicine. J Cell Physiol 213(2):341–347

    Article  CAS  PubMed  Google Scholar 

  3. Jiang XC, Xiang JJ, Wu HH, Zhang TY, Zhang DP, Xu QH, Huang XL, Kong XL, Sun JH, Hu YL, Li, Tabata Y, Shen YQ, Gao JQ (2019) Neural stem cells transfected with reactive oxygen species–responsive polyplexes for effective treatment of ischemic stroke. Adv Mater 31:1807591

    Article  Google Scholar 

  4. Khorraminejad-Shirazi M, Mohammad Farahmandnia B, Kardeh A, Estedlal S, Kardeh A Monabati (2018) Aging and stem cell therapy: AMPK as an applicable pharmacological target for rejuvenation of aged stem cells and achieving higher efficacy in stem cell therapy. Hematol Oncol Stem Cell Ther 11(4):189–194

    Article  CAS  PubMed  Google Scholar 

  5. Li J, Zhang J, Chen Y, Kawazoe N, Chen G (2017) TEMPO-Conjugated gold nanoparticles for reactive oxygen species scavenging and regulation of stem cell differentiation. ACS Appl Mater Interfaces 9(41):35683–35692

    Article  CAS  PubMed  Google Scholar 

  6. Stefanatos R, Sanz A (2017) The role of mitochondrial ROS in the aging brain. Federation of European Biochemical Societies 592(2018):743–758

  7. Ito K, Hirao A, Arai F, Matsuoka S, Takubo K, Hamaguchi I, Nomiyama K, Hosokawa K, Sakurada K, Nakagata N, Ikeda Y, Mak TW, Suda T (2004) Regulation of oxidative stress by ATM is required for self-renewal of haematopoietic stem cells. Nature 431(7011):997–1002

    Article  CAS  PubMed  Google Scholar 

  8. Lau A, Kennedy BK, Kirkland JL, Tullius SG (2019) Mixing old and young: enhancing rejuvenation and accelerating aging. J Clin Invest 129(1):4–11

    Article  PubMed  PubMed Central  Google Scholar 

  9. Zhao Y, Jia Z, Huang S, Wu Y, Liu L, Lin L, Wang D, He Q, Ruan D (2017) Age-related changes in nucleus pulposus mesenchymal stem cells: an in vitro study in rats. Stem Cells Int 6761572

  10. Rossi DJ, Jamieson CH, Weissman IL (2008) Stems cells and the pathways to aging and cancer. Cell 132(4):681–696

    Article  CAS  PubMed  Google Scholar 

  11. Liao N, Shi Y, Zhang C, Zheng Y, Wang Y, Zhao B, Zeng Y, Liu X, Liu J (2019) Antioxidants inhibit cell senescence and preserve stemness of adipose tissue-derived stem cells by reducing ROS generation during long-term in vitro expansion. Stem Cell Res Ther 10(1):306

    Article  PubMed  PubMed Central  Google Scholar 

  12. Tan SWS, Lee QY, Wong BSE, Cai Y, Baeg GH (2017) Redox homeostasis plays important roles in the maintenance of the Drosophila testis germline stem cells. Stem Cell Rep 9(1):342–354

    Article  CAS  Google Scholar 

  13. Denu and Hematti (2016) Effects of Oxidative Stress on Mesenchymal Stem Cell Biology. Oxidative Medicine and Cellular Longevity 2016:1–2

  14. Regmi S, Pathak S, Kim JO, Yong CS, Jeong JH (2019) Mesenchymal stem cell therapy for the treatment of inflammatory diseases: Challenges, opportunities, and future perspectives. Eur J Cell Biol 98(5–8):151041

    Article  CAS  PubMed  Google Scholar 

  15. Moya A, Paquet J, Deschepper M, Larochette N, Oudina K, Denoeud C et al (2018) Human mesenchymal stem cell failure to adapt to glucose shortage and rapidly use intracellular energy reserves through glycolysis explains poor cell survival after implantation. Stem Cells 36:363–376

    Article  CAS  PubMed  Google Scholar 

  16. Hu C, Li L (2018) Preconditioning influences mesenchymal stem cell properties in vitro and in vivo. J Cell Mol Med 22(3):1428–1442

    Article  PubMed  PubMed Central  Google Scholar 

  17. Valle-Prieto A, Conget PA (2010) Human mesenchymal stem cells efficiently manage oxidative stress. Stem Cells Dev 19(12):1885–1893

    Article  CAS  PubMed  Google Scholar 

  18. Li M, Yu L, She T et al (2012) Astragaloside IV attenuates toll-like receptor 4 expression via NF-kappaB pathway under high glucose condition in mesenchymal stem cells. Eur J Pharmacol 696:203–209

    Article  CAS  PubMed  Google Scholar 

  19. Zhang LY, Xue HG, Chen JY et al (2016) Genistein induces adipogenic differentiation in human bone marrow mesenchymal stem cells and suppresses their osteogenic potential by upregulating PPARgamma. Exp Ther Med 11:1853–1858

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Bhatti FU, Mehmood A, Latief N et al (2017) Vitamin E protects rat mesenchymal stem cells against hydrogen peroxide-induced oxidative stress in vitro and improves their therapeutic potential in surgically-induced rat model of osteoarthritis. Osteoarthritis Cartilage 25:321–331

    Article  CAS  PubMed  Google Scholar 

  21. Pourjafar M, Saidijam M, Mansouri K et al (2017) All-trans retinoic acid preconditioning enhances proliferation, angiogenesis and migration of mesenchymal stem cell in vitro and enhances wound repair in vivo. Cell Prolif 50:e12315

    Article  PubMed  Google Scholar 

  22. Joo HS, Suh JH, Lee HJ, Bang ES, Lee JM (2020) Current knowledge and future perspectives on mesenchymal stem cell-derived Exosomes as a New Therapeutic Agent. Int J Mol Sci 21(3):727

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Lin S, Zhao H, Xu C, Zhang P, Mei X, Jiang D (2023) Sulfasalazine-loaded nanoparticles for efficient inflammatory bowel disease therapy via ROS-scavenging strategy. Mater Design 225:111465

    Article  CAS  Google Scholar 

  24. Ishii T, Mimura I, Nagaoka K et al (2022) Effect of M2-like macrophages of the injured-kidney cortex on kidney cancer progression. Cell Death Discov 8:480

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Linares V, Alonso V, Domingo JL (2011) Oxidative stress as a mechanism underlying sulfasalazine-induced toxicity. Expert Opin Drug Saf 10(2):253–263

    Article  CAS  PubMed  Google Scholar 

  26. Kang C, Kim J, Ju S, Park S, Yoo J-W, Yoon I-S, Kim M-S, Jung Y (2022) Dapsone Azo-Linked with two Mesalazine Moieties is a “Me-Better” Alternative to Sulfasalazine. Pharmaceutics 14(3):684

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Tourani S, Behvandi A (2022) Synthesis of MIL-101(cr)/Sulfasalazine (Cr-TA@SSZ) hybrid and its use as a novel adsorbent for adsorptive removal of organic pollutants from wastewaters. J Porous Mater 29:1441–1462

    Article  CAS  Google Scholar 

  28. Kim JY, Cho HJ, Sir JJ, Kim BK, Hur J, Youn SW et al (2009) Sulfasalazine induces haem oxygenase-1 via ROS-dependent Nrf2 signalling, leading to control of neointimal hyperplasia. Cardiovasc Res 82(3):550–560

    Article  CAS  PubMed  Google Scholar 

  29. Joshi R, Kumar S, Unnikrishnan M, Mukherjee T (2005) Free radical scavenging reactions of sulfasalazine, 5-aminosalicylic acid and sulfapyridine: mechanistic aspects and antioxidant activity. Free Radic Res 39(11):1163–1172

    Article  CAS  PubMed  Google Scholar 

  30. Haneef K, Naeem N, Khan I, Iqbal H, Kabir N, Jamall S, Zahid M, Salim A (2014) Conditioned medium enhances the fusion capability of rat bone marrow mesenchymal stem cells and cardiomyocytes. Mol Biol Rep 41:3099–3112

    Article  CAS  PubMed  Google Scholar 

  31. Khan I, Ali A, Akhter MA, Naeem N, Chotani MA, Iqbal H, Kabir N, Atiq M, Salim A (2017) Epac-Rap1-activated mesenchymal stem cells improve cardiac function in rat model of myocardial infarction. Cardiovasc Ther 35(2)

  32. de Lange T (2002) Protection of mammalian telomeres. Oncogene 21(4):532–540

    Article  PubMed  Google Scholar 

  33. Costa TJ, Barros PR, Arce C, Santos JD, da Silva-Neto J, Egea G, Dantas AP, Tostes RC, Jiménez-Altayó F (2021) The homeostatic role of hydrogen peroxide, superoxide anion and nitric oxide in the vasculature. Free Radic Biol Med 162:615–635

    Article  CAS  PubMed  Google Scholar 

  34. Inoue T, Suzuki-Karasaki Y (2013) Mitochondrial superoxide mediates mitochondrial and endoplasmic reticulum dysfunctions in TRAIL-induced apoptosis in jurkat cells. Free Radic Biol Med 61:273–284

    Article  CAS  PubMed  Google Scholar 

  35. Bergaggio E, Piva R (2019 Apr 19) Wild-type IDH enzymes as actionable targets for Cancer Therapy. Cancers (Basel) 11(4):563

  36. Nakamura H (2005) Thioredoxin and its related molecules: update 2005. Antioxid Redox Signal 7(5–6):823–828

    Article  CAS  PubMed  Google Scholar 

  37. Tanaka C, Coling DE, Manohar S, Chen GD, Hu BH, Salvi R, Henderson D (2012) Expression pattern of oxidative stress and antioxidant defense-related genes in the aging Fischer 344/NHsd rat cochlea. Neurobiol Aging 33(8):1842e1–184214

    Article  Google Scholar 

  38. Carmel-Harel O, Stearman R, Gasch AP, Botstein D, Brown PO, Storz G (2001) Role of thioredoxin reductase in the Yap1p-dependent response to oxidative stress in Saccharomyces cerevisiae. Mol Microbiol 39(3):595–605

    Article  CAS  PubMed  Google Scholar 

  39. Cox AG, Winterbourn CC, Hampton MB (2009) Mitochondrial peroxiredoxin involvement in antioxidant defence and redox signalling. Biochem J 425(2):313–325

    Article  PubMed  Google Scholar 

  40. Younus H (2018) Therapeutic potentials of superoxide dismutase. Int J Health Sci (Qassim) 12(3):88–93

    CAS  PubMed  Google Scholar 

  41. Dynek JN, Smith S (2004) Resolution of sister telomere association is required for progression through mitosis. Science 304:97–100

    Article  CAS  PubMed  Google Scholar 

  42. Smogorzewska A, de Lange T (2004) Regulation of telomerase by telomeric proteins. Annu Rev Biochem 73:177–208

    Article  CAS  PubMed  Google Scholar 

  43. Tomás-Loba A, Flores I, Fernández-Marcos PJ, Cayuela ML, Maraver A, Tejera A, Borrás C, Matheu A, Klatt P, Flores JM, Viña J, Serrano M, Blasco MA (2008) Telomerase reverse transcriptase delays aging in cancer-resistant mice. Cell 135(4):609–622

    Article  PubMed  Google Scholar 

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Acknowledgements

This research article is dedicated to the memory of Dr. Siddiqua Jamall for her utmost support, guidance, and inspiration.

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Authors and Affiliations

  1. Dr. Panjwani Center for Molecular Medicine and Drug Research, International Center for Chemical and Biological Sciences, University of Karachi, Karachi, 75270, Pakistan

    Hana’a Iqbal & Asmat Salim

  2. Dow University of Health Sciences, Karachi, Pakistan

    Nadia Naeem

  3. Dr. Zafar H. Zaidi Center for Proteomics, University of Karachi, Karachi, 75270, Pakistan

    Kanwal Haneef

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  1. Hana’a Iqbal
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  2. Nadia Naeem
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  4. Asmat Salim
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Correspondence to Asmat Salim.

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Iqbal, H., Naeem, N., Haneef, K. et al. Sulfasalazine and Chromotrope 2B reduce oxidative stress in murine bone marrow-derived mesenchymal stem cells. Mol Biol Rep 50, 4119–4131 (2023). https://doi.org/10.1007/s11033-023-08321-8

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