Acta Scientific Pharmaceutical Sciences (ASPS)(ISSN: 2581-5423)

Research Article Volume 6 Issue 5

Dimethyl Fumarate Attenuates Kidney Ischemic Reperfusion Injury via Inflammatory and Oxidant Pathways

Sevda Shayesteh1, Sara Fazeli2 and Hamed Shafaroodi3*

1Pharmacology and Toxicology Department, Faculty of Pharmacy, Alborz University of Medical Sciences, Karaj, Iran
2Faculty of Pharmacy, Islamic Azad University, Tehran Medical Branch, Tehran, Iran
3Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran

*Corresponding Author: Hamed Shafaroodi, Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.

Received: January 04, 2022; Published: April 21, 2022


Purpose: Ischemia-reperfusion (IR) is one of the major causes of acute kidney injuries (AKI) as well as kidney transplant failure. Its underlying mechanisms include inflammatory, oxidant, and apoptotic pathways which result in nephron dysfunction. Dimethyl fumarate (DMF), is an immunomodulatory drug mostly used in multiple sclerosis, psoriasis, and auto-immune diseases. Regarding its anti-inflammatory and anti-oxidant history, this study aimed to investigate the effect of DMF on kidney IR by evaluating inflammatory and oxidant pathways.

Methods: The IR was induced by clamping the kidneys for 30 minutes. DMF was gavaged in 5, 15 and 45 mg/kg doses for 4 days pre-IR. The samples were collected on the 5th day of the experiment. Blood urea nitrogen (BUN) and creatinine were measured as markers of kidney function. Tumor necrosis factor (TNF-α) and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) levels were measured by enzyme-linked immunosorbent assay (ELISA) kits and Superoxide dismutase (SOD) and Glutathione S-transferase (GSH) levels were evaluated by pyrogallol and Ellman assays respectively.

Results: The 45 mg/kg dose of DMF was excluded from the study due to toxic effects. DMF (15 mg/kg) decreased the IR-induced BUN and creatinine as well as TNF-α and NF-κB levels. The SOD and GSH levels which were elevated in IR groups were reduced by DMF (15 mg/kg) administration.

Conclusion: It can be suggested that DMF attenuates IR development through anti-inflammatory and anti-oxidant pathways.

Keywords: Dimethyl Fumarate; Ischemia-reperfusion; Kidney; Nephroprotective


  1. Sawhney S., et al. “Acute kidney injury as an independent risk factor for unplanned 90-day hospital readmissions”. BMC Nephrology1 (2017): 1-13.
  2. P Basile D and C Yoder M. “Renal endothelial dysfunction in acute kidney ischemia reperfusion injury”. Cardiovascular and Haematological Disorders-Drug Targets1 (2014): 3-14.
  3. Nieuwenhuijs-Moeke GJ., et al. “Ischemia and reperfusion injury in kidney transplantation: relevant mechanisms in injury and repair”. Journal of Clinical Medicine1 (2020): 253.
  4. Prieto-Moure B., et al. “Allopurinol protective effect of renal ischemia by downregulating TNF-α, IL-1β, and IL-6 response”. Journal of Investigative Surgery3 (2017): 143-151.
  5. Gonullu E., et al. “Comparison of the effects of dexmedetomidine administered at two different times on renal ischemia/reperfusion injury in rats”. Brazilian Journal of Anesthesiology (English Edition)3 (2014): 152-158.
  6. Meng K., et al. “The Long Noncoding RNA Hotair Regulates Oxidative Stress and Cardiac Myocyte Apoptosis during Ischemia-Reperfusion”. Injury 2020 (2020).
  7. Jansen MP., et al. “Release of extracellular DNA influences renal ischemia reperfusion injury by platelet activation and formation of neutrophil extracellular traps”. Kidney International2 (2017): 352-364.
  8. Ratliff BB., et al. “Oxidant mechanisms in renal injury and disease”. Antioxidants and Redox Signaling3 (2016): 119-146.
  9. Friedewald JJ and Rabb HJKi. “Inflammatory cells in ischemic acute renal failure”. Kidney International2 (2004): 486-491.
  10. Blair HAJD. “Dimethyl fumarate: a review in moderate to severe plaque psoriasis”. Drugs 1 (2018): 123-130.
  11. Losavio FA., et al. “Transient hair loss during treatment with dimethyl-fumarate for multiple sclerosis”. Multiple Sclerosis and Related Disorders 7 (2016): 68-69.
  12. Heinz C and Heiligenhaus A. “Improvement of noninfectious uveitis with fumaric acid esters: results of a pilot study”. Archives of Ophthalmology4 (2007): 569-571.
  13. von Glehn F., et al. “Dimethyl fumarate downregulates the immune response through the HCA2/GPR109A pathway: implications for the treatment of multiple sclerosis”. Multiple Sclerosis and Related Disorders 23 (2018): 46-50.
  14. Tsubaki M., et al. “Dimethyl fumarate induces apoptosis of hematopoietic tumor cells via inhibition of NF-κB nuclear translocation and down-regulation of Bcl-xL and XIAP”. Biomedicine and Pharmacotherapy = Biomedecine and Pharmacotherapie8 (2014): 999-1005.
  15. Linker RA., et al. “Dimethyl fumarate for treatment of multiple sclerosis: mechanism of action, effectiveness, and side effects”. Current Neurology and Neuroscience Reports11 (2013): 1-7.
  16. Hu L., et al. “Erythropoietin ameliorates renal ischemia and reperfusion injury via inhibiting tubulointerstitial inflammation”. Journal of Surgical Research1 (2012): 260-266.
  17. Guo Y., et al. “Pretreatment of Huaiqihuang extractum protects against cisplatin-induced nephrotoxicity”. Scientific Reports1 (2018): 1-10.
  18. Marklund S and Marklund GJEjob. “Involvement of the superoxide anion radical in the autoxidation of pyrogallol and a convenient assay for superoxide dismutase”. European Journal of Biochemistry3 (1974): 469-474.
  19. Nostrandt A., et al. “A modified spectrophotometric method appropriate for measuring cholinesterase activity in tissue from carbaryl-treated animals”. Fundamental and Applied Toxicology2 (1993): 196-203.
  20. Malek M and Nematbakhsh MJJorip. “Renal ischemia/reperfusion injury; from pathophysiology to treatment”. Journal of Renal Injury Prevention2 (2015): 20.
  21. Silver SA., et al. “Causes of death after a hospitalization with AKI”. 29.3 (2018): 1001-1010.
  22. Yang M., et al. “Mitophagy and mitochondrial integrity in cardiac ischemia-reperfusion injury”. Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease9 (2019): 2293-2302.
  23. Kalogeris T., et al. “Mitochondrial reactive oxygen species: a double edged sword in ischemia/reperfusion vs preconditioning”. Redox Biology 2 (2014): 702-714.
  24. Hayyan M., et al. “Superoxide ion: generation and chemical implications”. Chemical Reviews5 (2016): 3029-3085.
  25. Nezamoleslami S., et al. “Glatiramer acetate attenuates renal ischemia reperfusion injury in rat model”. Experimental and Molecular Pathology 112 (2020): 104329.
  26. Zarrouk A., et al. “Attenuation of 7-ketocholesterol-induced overproduction of reactive oxygen species, apoptosis, and autophagy by dimethyl fumarate on 158 N murine oligodendrocytes”. The Journal of Steroid Biochemistry and Molecular Biology 169 (2017): 29-38.
  27. Bomprezzi RJTaind. “Dimethyl fumarate in the treatment of relapsing–remitting multiple sclerosis: an overview”. Therapeutic Advances in Neurological Disorders1 (2015): 20-30.
  28. Ozturk H., et al. “Carvacrol attenuates histopathogic and functional impairments induced by bilateral renal ischemia/reperfusion in rats”. Biomedicine and Pharmacotherapy = Biomedecine and Pharmacotherapie 98 (2018): 656-661.
  29. Kinsey GR., et al. “Inflammation in acute kidney injury”. Nephron Experimental Nephrology4 (2008): e102-e107.
  30. Al-Jaderi Z and Maghazachi AAJFii. “Utilization of dimethyl fumarate and related molecules for treatment of multiple sclerosis, cancer, and other diseases”. Frontiers in Immunology 7 (2016): 278.
  31. Smith MD., et al. “Dimethyl fumarate alters B‐cell memory and cytokine production in MS patients”. Annals of Clinical and Translational Neurology5 (2017): 351-355.
  32. Smith MD., et al. “Dimethyl fumarate treatment alters NK cell function in multiple sclerosis”. 48.2 (2018): 380-383.
  33. Peng H., et al. “Dimethyl fumarate inhibits dendritic cell maturation via nuclear factor κB (NF-κB) and extracellular signal-regulated kinase 1 and 2 (ERK1/2) and mitogen stress-activated kinase 1 (MSK1) signaling”. JBC33 (2012): 28017-28026.
  34. Faucher Q., et al. “Effects of Ischemia-Reperfusion on Tubular Cell Membrane Transporters and Consequences in Kidney Transplantation”. Journal of Clinical Medicine8 (2012): 2610.
  35. Zhao X., et al. “Glutathione antioxidant pathway activity and reserve determine toxicity and specificity of the biliary toxin biliatresone in zebrafish”. Hepatology 3 (2016): 894-907.
  36. Della Giustina A., et al. “Dimethyl fumarate modulates oxidative stress and inflammation in organs after sepsis in rats”. 41.1 (2018): 315-327.
  37. Takasu C., et al. “Treatment with dimethyl fumarate ameliorates liver ischemia/reperfusion injury”. World Journal of Gastroenterology25 (2017): 4508.
  38. Yuzbasioglu MF., et al. “Protective effects of propofol against ischemia/reperfusion injury in rat kidneys”. Renal Failure5 (2010): 578-583.


Citation: Hamed Shafaroodi., et al. “Forced Degradation Studies for Estimation of Finerenone by RP-HPLC Method". Acta Scientific Pharmaceutical Sciences 6.5 (2022): 08-14.


Copyright: © 2022 Hamed Shafaroodi., et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.


Acceptance rate32%
Acceptance to publication20-30 days

Indexed In

News and Events

  • Certification for Review
    Acta Scientific certifies the Editors/reviewers for their review done towards the assigned articles of the respective journals.
  • Submission Timeline for Upcoming Issue
    The last date for submission of articles for regular Issues is July 30, 2024.
  • Publication Certificate
    Authors will be issued a "Publication Certificate" as a mark of appreciation for publishing their work.
  • Best Article of the Issue
    The Editors will elect one Best Article after each issue release. The authors of this article will be provided with a certificate of "Best Article of the Issue"
  • Welcoming Article Submission
    Acta Scientific delightfully welcomes active researchers for submission of articles towards the upcoming issue of respective journals.

Contact US