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.
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
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