RESUMO
Lead halide perovskites (LHPs) are outstanding candidates for next-generation optoelectronic materials, with considerable prospects of use and commercial value. However, knowledge about their toxicity is scarce, which may limit their commercialization. Here, for the first time, we studied the cardiotoxicity and molecular mechanisms of representative CsPbBr3 nanoparticles in LHPs. After their intranasal administration to Institute of Cancer Research (ICR) mice, using advanced synchrotron radiation, mass spectrometry, and ultrasound imaging, we revealed that CsPbBr3 nanoparticles can severely affect cardiac systolic function by accumulating in the myocardial tissue. RNA sequencing and Western blotting demonstrated that CsPbBr3 nanoparticles induced excessive oxidative stress in cardiomyocytes, thereby provoking endoplasmic reticulum stress, disturbing calcium homeostasis, and ultimately leading to apoptosis. Our findings highlight the cardiotoxic effects of LHPs and provide crucial toxicological data for the product.
Assuntos
Compostos de Cálcio , Nanopartículas , Animais , Camundongos , Compostos de Cálcio/toxicidade , Miocárdio , Óxidos/toxicidade , Nanopartículas/toxicidadeRESUMO
Radiation-induced heart disease is a serious side effect of radiation therapy that can lead to severe consequences. However, effective and safe methods for their prevention and treatment are presently lacking. This study reports the crucial function of fullerenols in protecting cardiomyocytes from radiation injury. First, fullerenols are synthesized using a simple base-catalyzed method. Next, the as-prepared fullerenols are applied as an effective free radical scavenger and broad-spectrum antioxidant to protect against X-ray-induced cardiomyocyte injury. Their ability to reduce apoptosis via the mitochondrial signaling pathway at the cellular level is then verified. Finally, it is observed in animal models that fullerenols accumulate in the heart and alleviate myocardial damage induced by X-rays. This study represents a timely and essential analysis of the prevention and treatment of radiological myocardial injury, providing new insights into the applications of fullerenols for therapeutic strategies.
Assuntos
Fulerenos , Lesões por Radiação , Animais , Fulerenos/farmacologia , Fulerenos/uso terapêutico , Antioxidantes , Sequestradores de Radicais Livres , Miócitos CardíacosRESUMO
Radiation gastroenteritis represents one of the most prevalent and hazardous complications of abdominopelvic radiotherapy, which not only severely reduces patients' life quality but also restricts radiotherapy efficacy. However, there is currently no clinically available oral radioprotector for this threatening disease due to its complex pathogenesis and the harsh gastrointestinal environment. To this end, this study developed a facile but effective oral radioprotector, ergothioneine hyaluronate (EGT@HA) gel, protecting against radiation gastroenteritis by synergistically regulating oxidative stress, inflammation, and gut microbiota. In vitro and cellular experiments verified the chemical stability and free radical scavenging ability of EGT and its favorable cellular radioprotective efficacy by inhibiting intracellular reactive oxidative species (ROS) generation, DNA damage, mitochondrial damage, and apoptosis. At the in vivo level, EGT@HA with prolonged gastrointestinal residence mitigated radiation-induced gastrointestinal tissue injury, apoptosis, neutrophil infiltration, and gut flora dysbiosis. For the first time, this work investigated the protective effects of EGT@HA gel on radiation gastroenteritis, which not only hastens the advancement of the novel gastrointestinal radioprotector but also provides a valuable gastrointestinal radioprotection paradigm by synergistically modulating oxidative stress, inflammation, and gut microbiota disturbance.
Assuntos
Ergotioneína , Gastroenterite , Microbioma Gastrointestinal , Lesões por Radiação , Humanos , Ergotioneína/genética , Ergotioneína/farmacologia , Antioxidantes/farmacologia , Disbiose/tratamento farmacológico , Disbiose/prevenção & controle , Apoptose , Inflamação/tratamento farmacológico , Inflamação/prevenção & controleRESUMO
Objective To explore the role of autophagy, apoptosis of neutrophils and neutrophils extracellular traps (NET) formation in systemic lupus erythematosus (SLE). Methods Thirty-six patients with SLE were recruited as research subjects, and 32 healthy controls matched accordingly were enrolled as control subjects. The expression levels of microtubule associated protein 1 light chain 3B (LC3B), autophagy-related gene5(ATG5), P62, B-cell lymphoma 2(Bcl2), Bcl2-related X protein (BAX) in neutrophils were detected by Western blot analysis. Flow cytometry was employed to analyze the expression of LC3B on neutrophils. The expression level of myeloperoxidase(MPO) in plasma was estimated by ELISA. Furthermore, neutrophils were cultured in vitro and stimulated by 100 nmol/L rapamycin and 10 µg/mL lipopolysaccharide (LPS) for 6 hours, respectively. And then, the expression levels of LC3B, ATG5, P62, Bcl2 and BAX in neutrophils were detected by Western blot analysis. The level of MPO in culture supernatant was detected by ELISA. The change of fluorescence intensity of NET in culture supernatant was assayed by SytoxTM Green staining combined with fluorescence spectrophotometry. Results Compared with healthy controls, the levels of autophagy and apoptosis of neutrophils and NET formation in SLE patients were increased. The level of apoptosis and NET formation was positively associated with neutrophil autophagy. The level of autophagy showed an increase but had no effect on apoptosis and NET formation for neutrophil stimulated by rapamycin. The levels of autophagy and NET formation also increased with no significant effect on apoptosis for neutrophil induced by LPS. Conclusion The autophagy, apoptosis and NET formation of neutrophils increase in SLE patients. The activation of autophagy and NET in neutrophils possibly result from the inflammatory internal environment in SLE patients.