Selenium (Se) as one of the essential trace elements for human plays an important role in the oxidation reduction system. But the high toxicity of Se limits its application. In this case, the element Se with zero oxidation state (Se0) has captured our attention because of its low toxicity and excellent bioavailability. However, Se0 is very unstable and easily changes into the inactive form. By now many efforts have been done to protect its stability. And this work was conducted to explore the antioxidant capacities of the stable Se0 nanoparticles (SeNPs) stabilized using chitosan (CS) with different molecular weights (Mws) (CS-SeNPs). The different Mws CS-SeNPs could form uniform sphere particles with a size of about 103 nm after 30 days. The antioxidant tests of the DPPH, ABTS, and lipid peroxide models showed that these CS-SeNPs could scavenge free radicals at different levels. And the 1 month old SeNPs held the higher ABTS scavenging ability that the value could reach up to 87.45 ± 7.63% and 89.44 ± 5.03% of CS(l)-SeNPs and CS(h)-SeNPs, respectively. In the cell test using BABLC-3T3 or Caco-2, the production of the intracellular reactive oxygen species (ROS) could be inhibited in a Se concentration-dependent manner. The topical or oral administration of CS-SeNPs, particularly the Se nanoparticles stabilized with low molecular weight CS, CS(l)-SeNPs, and treated with a 30-day storage process, could efficiently protect glutathione peroxidase (GPx) activity and prevent the lipofusin formation induced by UV-radiation or d-galactose in mice, respectively. Such effects were more evident in viscera than in skin. The acute toxicity of CS(l)-SeNPs was tenfold lower than that of H2SeO3. Our work could demonstrate the CS-SeNPs hold a lower toxicity and a 30-day storage process could enhance the antioxidant capacities. All CS-SeNPs could penetrate the tissues and perform their antioxidant effects, especially the CS(l)-SeNPs in mice models. What’s more, the antioxidant capacities of CS-SeNPs were more evident in viscera than in skin.

Chronic kidney disease (CKD) is characterized by the accumulation of protein-bound uremic toxins (PBUTs), which play a pathophysiological role in renal fibrosis (a common pathological process resulting in CKD progression). Accumulation of the PBUT hippuric acid (HA) is positively correlated with disease progression in CKD patients, suggesting that HA may promote renal fibrosis. Oxidative stress is the most important factor affecting PBUTs nephrotoxicity. Herein, we assessed the ability of HA to promote kidney fibrosis by disrupting redox homeostasis. In HK-2 cells, HA increased fibrosis-related gene expression, extracellular matrix imbalance, and oxidative stress. Additionally, reactive oxygen species (ROS)-mediated TGFβ/SMAD signaling contributed to HA-induced fibrotic responses. HA disrupted antioxidant networks by decreasing the levels of nuclear factor erythroid 2-related factor 2 (NRF2), leading to ROS accumulation and fibrotic responses, as evidenced by NRF2 activation and knockdown. Moreover, NRF2 levels were reduced by NRF2 ubiquitination, which was regulated via increased interactions of Kelch-like ECH-associated protein 1 with Cullin 3 and NRF2. Finally, renal fibrosis and redox imbalance promoted by HA were confirmed in rats. Importantly, sulforaphane (NRF2 activator) reversed HA-promoted renal fibrosis. Thus, HA promotes renal fibrosis in CKD by disrupting NRF2-driven antioxidant system, indicating that NRF2 is a potential therapeutic target for CKD.