Our results showed that TP supplementation alleviated liver morphology, liver function and liver fibrosis; improved oxidative stress parameters; and increased the expression of STAT5b, Nrf2, HO-1 and NQO-1 and decreased the expression of Keap1 in the liver tissues of aged rats.
In this study, we found that the expression and activity of nuclear factor (erythroid-derived 2) - like 2 (Nrf2) were decreased in activated HSCs and negatively correlated with hepatic fibrosis severity in human liver specimens.
In in vivo system, Nrf2 knockdown mediated by Nrf2 shRNA lentivirus not only accelerated the lipid degradation in HSCs but also promoted the progression of CCl<sub>4</sub>-induced hepatic fibrosis in mice.
Hyperoside increased the activity of the antioxidant and phase II detoxifying enzymes through the activation of Nrf2 nuclear translocated in the CCl<sub>4</sub>-induced liver fibrosis mice.
Taken together, activation of I<sub>1</sub>R negatively regulates the progression of liver fibrosis in the Nrf2-dependent pathway, which suggests that specifically targeting I<sub>1</sub>R may be a potential therapeutic strategy for the treatment of liver fibrosis.
More importantly, this genomic analysis of nano-TiO2 treated HepG2 cells linked some of the in vitro canonical pathways to in vivo adverse outcomes: NRF2-mediated response pathways to oxidative stress, acute phase response to inflammation, cholesterol biosynthesis to steroid hormones alteration, fatty acid metabolism changes to lipid homeostasis alteration, G2/M cell checkpoint regulation to apoptosis, and hepatic fibrosis/stellate cell activation to liver fibrosis.