RESUMO
Aristolochic acid I (AAI), a component of aristolochic acids, can be converted to the toxic metabolite Aristolactam I (ALI) in vivo which forms aristolactam-nitrenium with delocalized positive charges. It is widely accepted that delocalized lipophilic cations can accumulate in mitochondria due to the highly negatively charged microenvironment of the mitochondrial matrix, but the uptake of ALI by mitochondria is not known. In this study, the cell uptake and mitochondrial localization of ALI, and its subsequent impact on mitochondrial function were investigated. Results show that ALI can rapidly penetrate HK-2 cells without relying on organic anion transporters 1/3 (OAT1/3). The cellular distribution of ALI was found to align with the observed distribution of a mitochondria-selective dye in HK-2 cells. Furthermore, the cell uptake and mitochondrial uptake of ALI were both inhibited by carbonyl cyanide 4-(trifluoromethoxy) phenylhydrazone, which induces mitochondrial membrane depolarization. These results suggest that ALI is selectively taken up by mitochondria. Consequently, mitochondrial dysfunction was observed after treatment with ALI. It should be noted that inhibiting OAT1/3 could result in an increased exposure of ALI in vivo and cause more seriously nephrotoxicity. In conclusion, this research reports the mitochondrial uptake of ALI and provides new insight on potential strategies for protection against AAI-induced nephrotoxicity.
Assuntos
Ácidos Aristolóquicos , Ácidos Aristolóquicos/toxicidade , MitocôndriasRESUMO
Constructing heterojunctions with vacancies has garnered substantial attention in the field of piezo-photocatalysis. However, the presence of interfacial vacancies can serve as charge-trapping sites, leading to the localization of electrons and hindering interfacial charge transfer. Herein, dual oxygen vacancies in the NiFe-layered double hydroxide and Bi2MoO6- x induced interfacial bonds have been designed for the piezo-photocatalytic N2 oxidation to NO3 -. Fortunately, it achieves sensational nitric acid production rates (7.23 mg g-1 h-1) in the absence of cocatalysts and sacrificial agents, which is 6.03 times of pure Bi2MoO6 that under ultrasound and light illumination. Theoretical and experimental results indicate that interfacial bonds act as "charge bridge" and "strain center" to break the carrier local effect and negative effects with piezocatalysis and photocatalysis for promoting exciton dissociation and charge transfer. Moreover, the strong electronic interaction of the interfacial bond induces internal reconstruction under ultrasound for promoting the local polarization and adsorption of N2, which accelerates the fracture of the N≡N bonds and reduces the activation energy of the reaction. The research not only establishes a novel approach for optimizing the combined effects of piezo-catalysis and photocatalysis, but also achieves equilibrium between the synergistic impacts of vacancies and heterojunctions.
RESUMO
Vacancies engineering has sparked a huge interest in enhancing photocatalytic activity, but monovacancy simultaneously conducts as either electron or hole acceptor and redox reaction, worsening charge transfer and catalytic performance. Here, the concept of electronic inversion has been proposed through the simultaneous introduction of surface oxygen and S vacancies in CdIn2S4 (OSv-CIS). Consequently, under mild conditions, the well-designed OSv-CIS-200 demonstrated a strong rate of N-benzylidenebenzylamine production (2972.07 µmol g-1 h-1) coupled with Hydrogen peroxide (H2O2) synthesis (2362.33 µmol g-1 h-1) (PIH), which is 12.4 times higher than that of CdIn2S4. Density functional theory (DFT) simulation and characterization studies demonstrate that oxygen is introduced into the lattice on the surface of the material, reversing the charge distribution of the S vacancy and enhancing the polarity of the total charge distribution. It not only provides a huge built-in electric field (BEF) for guiding the orientation of the charge transfer, but also acts as a long-distance active site to accelerate reaction and prevent H2O2 decomposition. Our work offers a straightforward connection between the atomic defect and intrinsic properties for designing high-efficiency materials.
RESUMO
Liver diseases caused by viral infections, alcoholism, drugs, or chemical poisons are a significant health problem: Liver diseases are a leading contributor to mortality, with approximately 2 million deaths per year worldwide. Liver fibrosis, as a common liver disease characterized by excessive collagen deposition, is associated with high morbidity and mortality, and there is no effective treatment. Numerous studies have shown that the accumulation of mast cells (MCs) in the liver is closely associated with liver injury caused by a variety of factors. This study investigated the relationship between MCs and carbon tetrachloride (CCl4)-induced liver fibrosis in rats and the effects of the MC stabilizers sodium cromoglycate (SGC) and ketotifen (KET) on CCl4-induced liver fibrosis. The results showed that MCs were recruited or activated during CCl4-induced liver fibrosis. Coadministration of SCG or KET alleviated the liver fibrosis by decreasing SCF/c-kit expression, inhibiting the TGF-ß1/Smad2/3 pathway, depressing the HIF-1a/VEGF pathway, activating Nrf2/HO-1 pathway, and increasing the hepatic levels of GSH, GSH-Px, and GR, thereby reducing hepatic oxidative stress. Collectively, recruitment or activation of MCs is linked to liver fibrosis and the stabilization of MCs may provide a new approach to the prevention of liver fibrosis.