No abstract

A novel chloro- and BF2bdk-substituted dithienylethene derivative, in which a chlorine atom and a difluoroboron β-diketonate (BF2bdk) group are appended at the termini of the dithienylethene core, is developed. The structure was confirmed by 1H NMR, 13C NMR, and high-resolution mass spectrometry (electrospray ionization). It displayed solvent-dependent photophysical properties, and blue/red light-triggered optical switching behavior in nonpolar or less polar solvents.

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Programmed cell death of renal tubular epithelial cells (RTECs) is the main pathophysiological mechanism of acute kidney injury (AKI). Copper-induced death is a newly discovered form of programmed cell death, mainly attributed to fatty acylation in the TCA cycle, which leads to mitochondrial stress and cell death. However, the role of copper-induced death in the occurrence and development of AKI remains unclear. In this study, we first identified that the expression of ferredoxin 1 (FDX1), a key gene for copper-induced death, was significantly increased in the renal tissues of patients with AKI. The expression of copper-induced death-related genes and copper transporter 1 (CTR1) was significantly increased in various animal models of AKI. Compared with the control group, in the hypoxia-reoxygenation (H/R), lipopolysaccharide, and cisplatin injury groups, the concentration of copper ions increased in the NRK-52E cells, and the expression of FDX1 and CTR1 proteins increased significantly. After the NRK-52E cells were stimulated by copper (Cu2+), elesclomol (ES), and Cu2+ + ES, the expression of CTR1 and FDX1 increased in the Cu2+ + ES group, and that of lactate dehydrogenase increased significantly. In addition, the expression of CTR1 and FDX1 in the tubular epithelial cells in the H/R model and cell death reduced significantly after siRNA knockdown of the FDX1 gene or copper chelation therapy with tetrathiomolybdate. Preliminary mechanism investigation showed that the expression of CTR1 and FDX1 in H/R tubular epithelial cells and cell death was significantly reduced following siRNA knockdown of the steroidogenic factor 1 gene. Therefore, we speculate that copper-induced death in the RTECs may play an important role in the pathogenesis of AKI. Additionally, SF1 may be involved in the regulation of cuproptosis during AKI.

Acute kidney injury (AKI) is mainly caused by ischemia-reperfusion (I/R), with high clinical mortality since there is a lack of definite and effective drug intervention except for renal replacement therapy. Previous research emphasized that ferroptosis is the pivotal process in I/R injury of renal. Ginsenoside Rb1 is a chemical compound belonging to the ginsenoside family and has been proved to have benefits for kidney diseases, but its specific mechanism in AKI is uncovered. Here we discovered Rb1 could mitigate ferroptosis in renal tubular epithelial cells of AKI animals. Mechanically, Rb1 significantly inhibited oxidative stress including promotion of GSH, reduction of malondialdehyde (MDA) and reactive oxygen species (ROS), also reduced inflammatory response, then relieved renal injury in I/R mice. RSL3, the inhibitor of GPX4, or Erastin, the inhibitor of SLC7A11, could induce ferroptosis and eliminate the protective effect of Rb1. Also, a ferroptosis inhibitor or ROS scavenger could simulate the protective effect of Rb1 on renal tubular epithelial cells. In conclusion, we confirmed that Rb1 promotes GSH synthesis by preventing oxidative stress, upregulating the expression of GPX4 and SLC7A11, and ultimately scavengers of ROS or MDA, and reduces the occurrence of ferroptosis in renal tubular epithelial cells. Rb1 has potential benefits for AKI patients.