Novel Nrf2 activators from microbial transformation products inhibit blood–retinal barrier permeability in rabbits

摘要: Background and Purpose Nuclear factor erythroid 2-related 2 (Nrf2) is a redox-sensitive transcription that binds to antioxidant response elements located in the promoter region of genes encoding many enzymes phase II detoxifying enzymes. Activation Nrf2 pathway seems protective for organs, although well-known activator, bardoxolone methyl, was evaluated clinically treating chronic kidney disease, it found induce adverse events. Many methyl derivatives, mostly derived by chemical modifications, have already been studied. However, we adopted biotransformation technique obtain novel activator. Experimental Approach The potent RS9, obtained from microbial transformation products. Its activity determining NADPH:quinone oxidoreductase-1 induction Hepa1c1c7 cells. We also investigated effects RS9 on oxygen-induced retinopathy rats glycated albumin-induced blood–retinal barrier permeability rabbits because ocular diseases are associated with oxidative stress inflammation. Key Results Bardoxolone doubled specific cells at much higher concentration than RS9. Moreover, Nrf2-targeted observed one-tenth lower Interestingly, cytotoxicity substantially reduced compared methyl. Oral intravitreal administration ameliorated pathological scores leakage models inflammation respectively. Conclusion Implications Nrf2 activators applicable potential as unique method prevention treatment retinovascular disease.