SpringerLink
Log in

Hydrogen Sulfide for Prevention of Obstructive Nephropathy

  • Chapter
  • First Online:
Hydrogen Sulfide in Kidney Diseases

  • 52 Accesses

Abstract

In prolonged complete unilateral ureteral obstruction, reduced renal blood flow places the kidney in a state of ischemia, which can cause tubular injury and inflammation. Infiltrating inflammatory cells release transforming growth factor-beta 1 (TGF-β1), a cytokine that initiates fibrosis through epithelial-mesenchymal transition (EMT) pathway. Persistent fibrosis can lead to irreversible renal injury and loss of renal function. While surgical intervention can remove the obstruction, relief of obstruction may not fully reverse renal injury. Additionally, patients often encounter long wait times between initial consultation and medical intervention, resulting in the accumulation of renal injury that may cause permanent dysfunction. Currently, accepted pharmacological therapies to mitigate the symptoms of obstructive nephropathy include acetaminophen, cyclooxygenase inhibitors, nonsteroidal anti-inflammatory medications, opioids, and alpha-receptor blockers. However, there is no evidence that they mitigate renal injury. Therefore, identifying potential therapies that could be administered during obstruction may help to improve renal function following decompression. Scientific evidence suggests that endogenously produced gasotransmitters can exhibit anti-inflammatory and antioxidant effects. Nitric oxide, carbon monoxide, and hydrogen sulfide have been identified as gasotransmitters and have been shown to have cytoprotective effects in various models of tissue injury. Studies have shown that treatment with sodium hydrogen sulfide (a hydrogen sulfide donor salt) mitigated TGF-β1 expression, oxidative stress, fibrosis, and inflammation associated with urinary obstruction. More recently, the use of more directed hydrogen sulfide donor molecules, such as GYY4137, has led to significant decreases in inflammation, fibrosis, and expression of EMT markers following urinary obstruction. Taken together, these findings suggest that hydrogen sulfide may be a novel potential therapy against obstructive nephropathy. This chapter focuses on the pathogenesis and treatment of obstructive nephropathy and proposes novel upcoming strategies that could improve patient outcomes.

This chapter is a modified version by the same authors in the publication titled Is Hydrogen Sulfide a Potential Novel Therapy to Prevent Renal Damage During Ureteral Obstruction? Nitric Oxide. 2018; 73:15–21.

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

Access this chapter

Log in via an institution

Subscribe and save

Springer+ Basic
EUR 32.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or Ebook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 119.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Hardcover Book
USD 159.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free ship** worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Similar content being viewed by others

References

  1. Roth KS, Koo HP, Spottswood SE, Chan JCM. Obstructive uropathy: an important cause chronic renal failure in children. Clin Pediatr (Phila). 2002;41:309–14.

    Article  PubMed  Google Scholar 

  2. Spernat D, Kourambas J. Urolithiasis—medical therapies. BJU Int. 2011;108:9–13.

    Article  PubMed  Google Scholar 

  3. Klahr S. Obstructive nephropathy. Intern Med. 2000;39(5):355–61.

    Article  CAS  PubMed  Google Scholar 

  4. Ucero AC, Benito-Martin A, Izquierdo MC, Sanchez-Niño MD, Sanz AB, Ramos AM, et al. Unilateral ureteral obstruction: beyond obstruction. Int Urol Nephrol. 2014;46(4):765–76.

    Article  PubMed  Google Scholar 

  5. Truong LD, Choi J-J, Tsao CC, Ayala G, Sheikh-Hamad D, Nassar G, et al. Renal cell apoptosis in chronic obstructive uropathy: the roles of caspases. Kidney Int. 2001;60:924–34.

    Article  CAS  PubMed  Google Scholar 

  6. Lech M, Anders H-J. Macrophages and fibrosis: how resident and infiltrating mononuclear phagocytes orchestrate all phases of tissue injury and repair. Biochim Biophys Acta. 2013;1832(7):989–97.

    Article  CAS  PubMed  Google Scholar 

  7. Kluth DC, Erwig L-P, Rees AJ. Multiple facets of macrophages in renal injury. Kidney Int. 2004;66:542–57.

    Article  CAS  PubMed  Google Scholar 

  8. Sakurai H, Hisada Y, Ueno M, Sugiura M, Kawashima K, Sugita T. Activation of transcription factor NF-kB in experimental glomerulonephritis in rats. Biochim Biophys Acta. 1996;1316:132–8.

    Article  PubMed  Google Scholar 

  9. Eddy AA, López-Guisa JM, Okamura DM, Yamaguchi I. Investigating mechanisms of chronic kidney disease in mouse models. Pediatr Nephrol. 2012;27(8):1233–47.

    Article  PubMed  Google Scholar 

  10. Samarakoon R, Overstreet JM, Higgins SP, Higgins PJ. TGF-β1 → SMAD/p53/USF2 → PAI-1 transcriptional axis in ureteral obstruction-induced renal fibrosis. Cell Tissue Res. 2012;347(1):117–28.

    Article  CAS  PubMed  Google Scholar 

  11. Chevalier RL. Pathogenesis of renal injury in obstructive uropathy. Curr Opin Pediatr. 2006;18(2):153–60.

    Article  PubMed  Google Scholar 

  12. Iwano M, Neilson EG. Mechanisms of tubulointerstitial fibrosis. Curr Opin Nephrol Hypertens. 2004;13:279–84.

    Article  PubMed  Google Scholar 

  13. Kaneto H, Morrissey J, Klahr S. Increased expression of TGF-β1 mRNA in the obstructed kidney of rats with unilateral ureteral ligation. Kidney Int. 1993;44(2):313–21.

    Article  CAS  PubMed  Google Scholar 

  14. Manucha W, Oliverros L, Carrizo L, Seltzer A, Valles P. Losartan modulation on NOS isoforms and COX-2 expression in early renal fibrogenesis in unilateral obstruction. Kidney Int. 2004;65:2091–107.

    Article  CAS  PubMed  Google Scholar 

  15. Gibbons GH, Pratt RE, Dzau VJ. Vascular smooth muscle cell hypertrophy vs. hyperplasia autocrine transforming growth factor beta 1, expression determines growth response to angiotensin II. J Clin Invest. 1992;90:456–61.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Xu J, Lamouille S, Derynck R. TGF-beta-induced epithelial to mesenchymal transition. Cell Res. 2009;19(2):156–72.

    Article  CAS  PubMed  Google Scholar 

  17. Vaughan ED Jr, Gillenwater JY. Recovery following complete chronic unilateral ureteral occlusion: functional, radiographic and pathologic alterations. J Urol. 1971;106:27–35.

    Article  PubMed  Google Scholar 

  18. Chevalier RL, Kim A, Thornhill BA, Wolstenholme JT. Recovery following relief of unilateral ureteral obstruction in the neonatal rat. Kidney Int. 1999;55:793–807.

    Article  CAS  PubMed  Google Scholar 

  19. Chaabane W, Praddaude F, Buleon M, Jaafar A, Vallet M, Rischmann P, et al. Renal functional decline and glomerulotubular injury are arrested but not restored by release of unilateral ureteral obstruction (UUO). Am J Physiol Ren Physiol. 2013;304(4):F432–9.

    Article  CAS  Google Scholar 

  20. Chevalier RL, Forbes MS, Thornhill BA. Ureteral obstruction as a model of renal interstitial fibrosis and obstructive nephropathy. Kidney Int. 2009;75(11):1145–52.

    Article  PubMed  Google Scholar 

  21. Tapmeier TT, Brown KL, Tang Z, Sacks SH, Sheerin NS, Wong W. Reimplantation of the ureter after unilateral ureteral obstruction provides a model that allows functional evaluation. Kidney Int. 2008;73(7):885–9.

    Article  CAS  PubMed  Google Scholar 

  22. York NE, Borofsky MS, Lingeman JE. Risks associated with drug treatments for kidney stones. Expert Opin Drug Saf. 2015;14:1865–77.

    Article  CAS  PubMed  Google Scholar 

  23. Kerr WS Jr. Effects of complete ureteral obstruction in dogs on kidney function. Am J Phys. 1956;184:521–6.

    Article  Google Scholar 

  24. Wu AK, Tran TC, Sorensen MD, Durack JC, Stoller ML. Relative renal function does not improve after relieving chronic renal obstruction. BJU Int. 2012;109(10):1540–4.

    Article  PubMed  Google Scholar 

  25. Wang R. Two’s company, three’s a crowd: can H2S be the third endogenous gaseous transmitter? FASEB J. 2002;16(13):1792–8.

    Article  CAS  PubMed  Google Scholar 

  26. Qian Y, Matson JB. Gasotransmitter delivery via self-assembling peptides: treating diseases with natural signaling gases. Adv Drug Deliv Rev. 2017;110:137–56.

    Article  PubMed  Google Scholar 

  27. Sharma JN, Al-Omran A, Parvathy SS. Role of nitric oxide in inflammatory diseases. Inflammopharmacology. 2007;15(6):252–9.

    Article  CAS  PubMed  Google Scholar 

  28. Lefer AM, Lefer DJ. Nitric oxide. II. Nitric oxide protects in intestinal inflammation. Am J Phys. 1999;276(3 Pt 1):G572–5.

    CAS  Google Scholar 

  29. Sun D, Wang Y, Liu C, Zhou X, Li X, **ao A. Effects of nitric oxide on renal interstitial fibrosis in rats with unilateral ureteral obstruction. Life Sci. 2012;90(23–24):900–9.

    Article  CAS  PubMed  Google Scholar 

  30. Gibbons SJ, Farrugia G. The role of carbon monoxide in the gastrointestinal tract. J Physiol. 2004;556(Pt 2):325–36.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Motterlini R, Foresti R. Heme oxygenase-1 as a target for drug discovery. Antioxid Redox Signal. 2013;20(11):1810–26.

    Article  Google Scholar 

  32. Abe T, Fu**o M, Yazawa K, Imamura R, Hatayama N, Kakuta Y, Tsutahara K, Okumi M, Ichimaru N, Kaimori JY, Isaka Y, Seki K, Takahara S, Li X-K, Nonomura N. High-pressure carbon monoxide preserves rat kidney grafts from apoptosis and inflammation. Lab Investig. 2017;97:468–77.

    Article  CAS  PubMed  Google Scholar 

  33. Bauer I, Pannen BHJ. Bench-to-bedside review: carbon monoxide—from mitochondrial poisoning to therapeutic use. Crit Care. 2009;13(4):1–10.

    Article  Google Scholar 

  34. Wallace JL, Ianaro A, Flannigan KL, Cirino G. Gaseous mediators in resolution of inflammation. Semin Immunol. 2015;27(3):227–33.

    Article  CAS  PubMed  Google Scholar 

  35. Whiteman M, Le Trionnaire S, Chopra M, Fox B, Whatmore J. Emerging role of hydrogen sulfide in health and disease: critical appraisal of biomarkers and pharmacological tools. Clin Sci. 2011;121(11):459–88.

    Article  CAS  Google Scholar 

  36. Lobb I, Sonke E, Aboalsamh G, Sener A. Hydrogen sulphide and the kidney: important roles in renal physiology and pathogenesis and treatment of kidney injury and disease. Nitric Oxide. 2014;46(2015):55–65.

    PubMed  Google Scholar 

  37. Yamamoto J, Sato W, Kosugi T, Yamamoto T, Kimura T, Taniguchi S, et al. Distribution of hydrogen sulfide (H2S)-producing enzymes and the roles of the H2S donor sodium hydrosulfide in diabetic nephropathy. Clin Exp Nephrol. 2013;17(1):32–40.

    Article  CAS  PubMed  Google Scholar 

  38. **a M, Chen L, Muh RW, Li P, Li N. Production and actions of hydrogen sulfide, a novel gaseous bioactive substance, in the kidneys. J Pharmacol Exp Ther. 2006;329(3):1056–62.

    Article  Google Scholar 

  39. Xue H, Yuan P, Ni J, Li C, Shao D, Liu J, et al. H2S inhibits hyperglycemia-induced intrarenal renin–angiotensin system activation via attenuation of reactive oxygen species generation. PLoS One. 2013;8(9):e74366.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Jung K-J, Jang H-S, Kim JI, Han SJ, Park J-W, Park KM. Involvement of hydrogen sulfide and homocysteine transsulfuration pathway in the progression of kidney fibrosis after ureteral obstruction. Biochim Biophys Acta. 2013;1832(12):1989–97.

    Article  CAS  PubMed  Google Scholar 

  41. Song K, Li Q, Yin X-Y, Lu Y, Liu C-F, Hu L-F. Hydrogen sulfide: a therapeutic candidate for fibrotic disease? Oxid Med Cell Longev. 2015;2015:458720.

    Article  PubMed  PubMed Central  Google Scholar 

  42. Whiteman M, Armstrong JS, Chu SH, Jia-Ling S, Wong BS, Cheung NS, et al. The novel neuromodulator hydrogen sulfide: an endogenous peroxynitrite “scavenger”? J Neurochem. 2004;90(3):765–8.

    Article  CAS  PubMed  Google Scholar 

  43. Deng Y. Protective effects of hydrogen sulfide on oxidative stress and fibrosis in hepatic stellate cells. Mol Med Rep. 2012;7:247–53.

    PubMed  Google Scholar 

  44. Jiang D, Zhang Y, Yang M, Wang S, Jiang Z, Li Z. Exogenous hydrogen sulfide prevents kidney damage following unilateral ureteral obstruction. Neurourol Urodyn. 2014;33:538–43.

    Article  CAS  PubMed  Google Scholar 

  45. Cao H, Zhou X, Zhang J, Huang X, Zhai Y, Zhang X, et al. Hydrogen sulfide protects against bleomycin-induced pulmonary fibrosis in rats by inhibiting NF-κB expression and regulating Th1/Th2 balance. Toxicol Lett. 2014;224(3):387–94.

    Article  CAS  PubMed  Google Scholar 

  46. Szabó C. Hydrogen sulphide and its therapeutic potential. Nat Rev Drug Discov. 2007;6(11):917–35.

    Article  PubMed  Google Scholar 

  47. Lobb I, Mok A, Lan Z, Liu W, Garcia B, Sener A. Supplemental hydrogen sulphide protects transplant kidney function and prolongs recipient survival after prolonged cold ischemia-reperfusion injury by mitigating renal graft apoptosis and inflammation. BJU Int. 2012;110(11 Pt C):E1187–95.

    CAS  PubMed  Google Scholar 

  48. Dursun M, Alper O, Emin O, Suleyman S, Huseyin B, Ozgur DO, Cekmen Mustafa NO, Somay A. Protective effect of hydrogen sulfide on protective effect of hydrogen sulfide on renal injury in the experimental unilateral ureteral obstruction-induced renal injury. Int Braz J Urol. 2015;41:1185–93.

    Article  PubMed  PubMed Central  Google Scholar 

  49. Song K, Wang F, Li Q, Shi Y-B, Zheng H-F, Peng H, et al. Hydrogen sulfide inhibits the renal fibrosis of obstructive nephropathy. Kidney Int. 2014;85(6):1318–29.

    Article  CAS  PubMed  Google Scholar 

  50. Meng X-M, Nikolic-Paterson DJ, Lan HY. Inflammatory processes in renal fibrosis. Nat Rev Nephrol. 2014;10(9):493–503.

    Article  CAS  PubMed  Google Scholar 

  51. Zhang S, Pan C, Zhou F, Yuan Z, Wang H, Cui W, et al. Hydrogen sulfide as a potential therapeutic target in fibrosis. Oxid Med Cell Longev. 2015;2015:593407.

    Article  PubMed  PubMed Central  Google Scholar 

  52. Fang L-P, Lin Q, Tang C-S, Liu X-M. Hydrogen sulfide attenuates epithelial-mesenchymal transition of human alveolar epithelial cells. Pharmacol Res. 2010;61(4):298–305.

    Article  CAS  PubMed  Google Scholar 

  53. Zheng D, Dong S, Li T, Yang F, Yu X, Wu J, et al. Exogenous hydrogen sulfide attenuates cardiac fibrosis through reactive oxygen species signal pathways in experimental diabetes mellitus models. Cell Physiol Biochem. 2015;36(3):917–29.

    Article  CAS  PubMed  Google Scholar 

  54. Lin S, Visram F, Liu W, Haig A, Jiang J, Mok A, et al. GYY4137, a slow-releasing hydrogen sulfide donor, ameliorates renal damage associated with chronic obstructive uropathy. J Urol. 2016;196:1778–87.

    Article  CAS  PubMed  Google Scholar 

  55. Guo L, Peng W, Tao J, Lan Z, Hei H, Tian L, et al. Hydrogen sulfide inhibits transforming growth factor-β1-induced EMT via Wnt/catenin pathway. PLoS One. 2016;11(1):e01470181.

    Article  Google Scholar 

  56. Li L, Whiteman M, Guan YY, Neo KL, Cheng Y, Lee SW, et al. Characterization of a novel, water-soluble hydrogen sulfide-releasing molecule (GYY4137): new insights into the biology of hydrogen sulfide. Circulation. 2008;117(18):2351–60.

    Article  CAS  PubMed  Google Scholar 

  57. Li L, Fox B, Keeble J, Salto-Tellez M, Winyard PG, Wood ME, et al. The complex effects of the slow-releasing hydrogen sulfide donor GYY4137 in a model of acute joint inflammation and in human cartilage cells. J Cell Mol Med. 2013;17(3):365–76.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. Wallace JL, Vaughan D, Dicay M, MacNaughton WK, DeNucci G. Hydrogen sulfide-releasing therapeutics: translation to the clinic. Antioxid Redox Signal. 2018;28(16):1533–40.

    Article  CAS  PubMed  Google Scholar 

  59. Szabo C, Papapetropoulos A. International union of basic and clinical pharmacology. CII: pharmacological modulation of H2S levels: H2S donors and H2S biosynthesis inhibitors. Pharmacol Rev. 2017;69(4):497–564.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. Zhao W, Zhang J, Lu Y, Wang R. The vasorelaxant effect of H2S as a novel endogenous gaseous KATP channel opener. EMBO J. 2001;20(21):6008–16.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. Altaany Z, Yang G, Wang R. Crosstalk between hydrogen sulfide and nitric oxide in endothelial cells. J Cell Mol Med. 2013;17(7):879–88.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  62. Hanna N, Cardin S, Leung TK, Nattel S. Differences in atrial versus ventricular remodeling in dogs with ventricular tachypacing-induced congestive heart failure. Cardiovasc Res. 2004;63(2):236–44.

    Article  CAS  PubMed  Google Scholar 

  63. Kondo K, Bhushan S, King A, Prabhu S, Hamid T, Koenig S, et al. H2S protects against pressure overload induced heart failure via upregulation of endothelial nitric oxide synthase (eNOS). Circulation. 2014;127(10):1116–27.

    Article  Google Scholar 

  64. Feliers D, Lee HJHJ, Kasinath BSBS. Hydrogen sulfide in renal physiology and disease. Antioxid Redox Signal. 2016;25(13):720–31.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  65. Zhou X, Feng Y, Zhan Z, Chen J. Hydrogen sulfide alleviates diabetic nephropathy in a streptozotocin-induced diabetic rat model. J Biol Chem. 2014;289(42):28827–34.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Microbiology and Immunology, Schulich School of Medicine and Dentistry, University of Western Ontario, London, ON, Canada

    Shouzhe Lin, Smriti Juriasingani & Alp Sener

  2. Matthew Mailing Centre for Translational Transplant Studies, University Hospital, London Health Sciences Centre, London, ON, Canada

    Shouzhe Lin, Smriti Juriasingani, George J. Dugbartey & Alp Sener

  3. Department of Surgery, Schulich School of Medicine and Dentistry, St. Joseph’s Health Care London, London, ON, Canada

    George J. Dugbartey & Alp Sener

  4. Department of Pharmacology and Toxicology, School of Pharmacy, College of Health Sciences, University of Ghana, Accra, Ghana

    George J. Dugbartey

  5. Department of Physiology and Pharmacology, Accra College of Medicine, Accra, Ghana

    George J. Dugbartey

Authors
  1. Shouzhe Lin
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Smriti Juriasingani
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. George J. Dugbartey
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Alp Sener
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to George J. Dugbartey .

Ethics declarations

None.

Rights and permissions

Reprints and permissions

Copyright information

© 2023 The Author(s), under exclusive license to Springer Nature Switzerland AG

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Lin, S., Juriasingani, S., Dugbartey, G.J., Sener, A. (2023). Hydrogen Sulfide for Prevention of Obstructive Nephropathy. In: Hydrogen Sulfide in Kidney Diseases. Springer, Cham. https://doi.org/10.1007/978-3-031-44041-0_7

Download citation

  • DOI: https://doi.org/10.1007/978-3-031-44041-0_7

  • Published:

  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-031-44040-3

  • Online ISBN: 978-3-031-44041-0

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation