| Popis: |
Introduction: Dimethyl fumarate (DMF), the methyl ester of fumaric acid, exhibited various pharmacological effects. The aim of this study was to clarify the potential nephroprotective effect of DMF against DEHP-induced nephrotoxicity. Methods: HEK-293 cells were exposed to different concentrations of DMF plus IC50 concentrations of monoethylhexyl phthalate (MEHP) to evaluate possible cytoprotective effect of DMF. For more evaluation, rats were divided into 7 groups (n=6 per group). Corn oil group, DEHP group (200 mg/kg dissolved in corn oil by gavage). DMF (15, 30, and 60 mg/kg) plus DEHP (200 mg/kg) groups, vitamin E (20 mg/kg) plus DEHP (200 mg/kg) group and DMF (60 mg/kg) alone (45 days). Results: DMF significantly decrease MEHP-induced cytotoxicity DMF improved BUN and creatinine levels compared to DEHP in a dose-dependent manner. Furthermore, DEHP-induced mitochondrial dysfunction was reduced by DMF. To determine the molecular signaling involved in the nephroprotective effects of DMF, the expression of the p65 nuclear factor kappa B (NFκB), tumor necrosis factor alpha (TNFα), nuclear factor E2-related factor 2 (Nrf2), and heme oxygenase-1 (HO-1) genes was measured by real-time PCR. p65NFκB and TNFα expression was increased, whereas Nrf2 and HO-1 expression was decreased in the DEHP group compared to the control group. These effects were reversed by using DMF. Conclusions: The findings of the current study revealed that DMF can act as a nephroprotective agent against kidney damage induced by DEHP partly through inhibiting NFκB and improving Nrf2 signaling pathways. |
