Sodium aescinate induces renal toxicity by promoting Nrf2/GPX4-mediated ferroptosis.

Sodium aescinate (SA) is extracted from Aesculus wilsonii Rehd seeds and was first marketed as a medicament in German. With the wide application of SA in clinical practice, reports of adverse drug reactions and adverse events have gradually increased, including renal impairment. However, the pathogenic mechanisms of SA have not yet been fully elucidated. The toxic effects and underlying mechanisms of SA were explored in this study. Our data showed that SA significantly elevated the levels of blood urea nitrogen (BUN), serum creatinine (Scr) and Kidney injury molecule 1 (Kim-1), accompanied by pathologically significant changes in renal tissue. SA induced NRK-52E cell death and disrupted the integrity of the cell membrane. Moreover, SA caused significant reductions in FTH, Nrf2, xCT, GPX4, and FSP1 levels, but increased TFR1 and ACSL4 levels. SA decreased glutathione peroxidase (GPx), glutathione (GSH) and cysteine (Cys) levels, but improved Fe2+, malondialdehyde (MDA), reactive oxygen species (ROS) and lipid peroxidation levels, ultimately leading to the induction of ferroptosis. Importantly, inhibition of ferroptosis or activation of the Nrf2/GPX4 pathway prevented SA-induced nephrotoxicity. These findings indicated that SA induced oxidative damage and ferroptosis-mediated kidney injury by suppressing the Nrf2/GPX4 axis activity.

Sodium Selenite Prevents Matrine-Induced Nephrotoxicity by Suppressing Ferroptosis via the GSH-GPX4 Antioxidant System.

Matrine (MT), an active ingredient derived from Sophor flavescens Ait, is used as a therapeutic agent to treat liver disease and cancer. However, the serious toxic effects of MT, including nephrotoxicity, have limited its clinical application. Here, we explored the involvement of ferroptosis in MT-induced kidney injury and evaluated the potential efficacy and underlying mechanism of sodium selenite (SS) in attenuating MT-induced nephrotoxicity. We found that MT not only disrupts renal structure in mice but also induces the death of NRK-52E cells. Additionally, MT treatment resulted in significant elevations in ferrous iron, reactive oxygen species (ROS) and lipid peroxidation levels, accompanied by decreases in glutathione (GSH) and glutathione peroxidase (GPx) levels. SS effectively mitigated the alterations in ferroptosis-related indicators caused by MT and prevented MT-induced nephrotoxicity as effectively as Fer-1 in vivo and in vitro. SS also reversed the MT-induced reduction in GPX4, CTH and xCT protein levels. However, the glutathione peroxidase 4 (GPX4) inhibitor RSL3 and knockdown of GPX4, CTH, or xCT via siRNA abolished the protective effect of SS against MT-induced nephrotoxicity, indicating that SS exhibited antiferroptotic effects via the GSH-GPX4 antioxidant system. Overall, MT-induced ferroptosis triggers nephrotoxicity, and SS is a promising therapeutic drug for alleviating MT-induced renal injury by activating the GSH-GPX4 axis.

A new dual-ion battery based on amorphous carbon.

The Na-based dual-ion batteries (NDIBs), combining the advantages of Na-ion batteries and dual-ion batteries, are attracting more attention due to their merits of abundant source, low cost and high energy density. However, the main challenges faced by NDIBs are their low capacity and poor cycling. Herein, we report a new ion storage mechanism for high-performance NDIBs using amorphous carbon (AOMC) as cathode. Unlike the graphite carbon that can only accommodate the PF6- anion (typical DIB system), the AOMC herein can both accommodate Na+ cation and PF6- anion due to its amorphous feature, which is conceptually new dual-ion system for achieving much higher capacity. Ex-situ X-ray photoelectron spectroscopy, X-ray diffraction and Raman studies reveal that the disordered carbon in the AOMC can be transformed to the partial graphitic stacking in short range, improving both capacity and cycling stability of NDIBs. As a consequence, the AOMC delivers a highly reversible storage capacity of 136 mAh g-1 for 800 cycles at a very high current density of 2.0 A g-1, much higher than all the reported NDIBs. Such concept can be generalized to develop high-performance dual-ion full cell using sodium ion pre-intercalated materials as anode and AOMC as cathode.

Hydrogenated Na2Ti3O7 Epitaxially Grown on Flexible N-Doped Carbon Sponge for Potassium-Ion Batteries.

With its inherent zig-zag layered structure and open framework, Na2Ti3O7 (NTO) is a promising anode material for potassium-ion batteries (KIBs). However, its poor electronic conductivity caused by large band gap (∼3.7 eV) usually leads to low-performance KIBs. In this work, we synthesize the fluff-like hydrogenated Na2Ti3O7 (HNTO) nanowires grown on N-doped carbon sponge (CS) as a binder-free and current-collector-free flexible anode for KIBs (denoted as HNTO/CS). High-resolution X-ray photoelectron spectroscopy (XPS) and electron spin-resonance spectroscopy (ESR) confirm the existence of Ti-OHs and O vacancies in HNTO. The first-principles calculation discloses that both Ti-OHs and O vacancies are equivalent to n-type doping because they can shift the Fermi level up to the conduction band, thus leading to a higher electronic conductivity and better performance for KIBs. In addition, the N-doped CS can further reinforce the conductivity and avoid the aggregation of HNTO nanowires during cycling. As a result, the as-made HNTO/CS can deliver a capacity of 107.8 mAh g-1 at 100 mA g-1 after 20 cycles, and keep the capacity of 90.9% and 82.5% after 200 and 1555 cycles, respectively, much better than the samples without hydrogenation treatment or N-doped CS and reported KTi xO y-based materials. Our work highlights the importance of hydrogenation treatment and N-doped CS in enhancing the electrochemical property for KIBs.