Omega-3 fatty acids upregulate Nrf2 expression and attenuate apoptosis, inflammation, and fibrosis in a rat model of cyclosporine-induced nephropathy

Abstract

Background: Cyclosporine A (CsA)-induced kidney injury is characterized by renal impairment with inflammatory cell infiltrations, apoptosis, fibrosis, and hypoxic injury. It is not clear whether omega-3 fatty acids (O-3 FAs), which have anti-inflammatory and antioxidant roles, affect nuclear factor erythroid 2-related factor 2 (Nrf2) expression. The aim of this study was to investigate whether O-3 FAs affect Nrf2 expression and exert anti-inflammatory, anti-apoptotic, and anti-fibrotic effects in CsA-induced nephropathy.Methods: Male Sprague-Dawley rats were divided into control, CsA-treated, and CsA-treated with O-3 FA groups. Nrf2 expression was measured by Western blots and immunohistochemical staining.Results: Kidney function was impaired in the CsA-treated rats compared to the controls. Caspase-3 and caspase-7 were activated in the CsA-treated group, and the Bax/Bcl2 ratio was higher. O-3 FAs attenuated these apoptosis-related changes. ED-1 and inhibition of kappa B (IĸB) protein expression were significantly upregulated in the CsA-treated group. Compared to the control group, O-3 FA supplementation attenuated the increased expression of ED-1 and IĸB related to inflammation. Smad2/3, Smad4, and transforming growth factor-β1 were activated in the CsA group, and O-3 FA treatment prevented these changes related to renal fibrosis. The expression of Nrf2 was reduced in CsA-treated rats, but Nrf-2 was increased by O-3 FA treatment.Conclusions: We suggest that Nrf2 is a potential mediator induced by O-3 FA supplementation and that it attenuates pro-inflammatory pathways, fibrotic processes, and apoptosis. Further studies are needed to elucidate the crosstalk between Nrf2 expression and signals related to O-3 FA treatment.