The dual reno- and neuro-protective effects of dimethyl fumarate against uremic encephalopathy in a renal ischemia/reperfusion model.

Pharmacological Reports : PR
Diaa RagabHanan S El-Abhar

Abstract

Dimethyl fumarate (DMF), a Nrf2 activator approved for multiple sclerosis (MS) in 2013, showed promising antioxidant and anti-inflammatory effects against cerebral injury. However, its mechanistic maneuver in renal ischemia/reperfusion (I/R) injury and its associated uremic encephalopathy has not been previously highlighted. To fulfill this aim, rats were divided into 4 groups; sham-operated, renal I/R, and 14 days pretreated DMF (15 and 25 mg/kg/day, orally). The small molecule drug reduced renal I/R-induced elevation in serum creatinine and blood urea nitrogen, the renal content of interleukin (IL)-18 and its pro-activator caspase-1. The DMF antioxidant potential was confirmed by the increased renal Nrf2 mRNA expression/content associated wit an enhanced total antioxidant capacity and an inhibition of lipid peroxidation. This character entailed the suppression of the assessed inflammatory markers, such as nuclear factor (NF)-κB, p38 mitogen-activated protein kinase, and tumor necrosis factor-α. Remotely, DMF protected against uremic encephalopathy signified by the suppressed cortical/hippocampal contents of glial fibrillary acidic protein through suppressing 2 trajectories, the NF-κB/inducible nitric oxide synthase/nitric oxi...Continue Reading

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