MnO2 nanoparticles trigger hepatic lipotoxicity and mitophagy via mtROS-dependent Hsf1Ser326 phosphorylation.

Manganese (Mn) is an essential element for maintaining normal metabolism in vertebrates. Mn dioxide nanoparticles (MnO2 NPs), a novel Mn source, have shown great potentials in biological and biomedical applications due to their distinct physical and chemical properties. However, little is known about potential adverse effects on animal or cellular metabolism. Here, we investigated whether and how dietary MnO2 NPs affect hepatic lipid metabolism in vertebrates. We found that, excessive MnO2 NPs intake increased hepatic and mitochondrial Mn content, promoted hepatic lipotoxic disease and lipogenesis, and inhibited hepatic lipolysis and fatty acid ß-oxidation. Moreover, excessive MnO2 NPs intake induced hepatic mitochondrial oxidative stress, damaged mitochondrial function, disrupted mitochondrial dynamics and activated mitophagy. Importantly, we uncovered that mtROS-activated phosphorylation of heat shock factor 1 (Hsf1) at Ser326 residue mediated MnO2 NPs-induced hepatic lipotoxic disease and mitophagy. Mechanistically, MnO2 NPs-induced lipotoxicity and mitophagy were via mtROS-induced phosphorylation and nucleus translocation of Hsf1 and its DNA binding capacity to plin2/dgat1 and bnip3 promoters, respectively. Overall, our findings uncover novel mechanisms by which mtROS-mediated mitochondrial dysfunction and phosphorylation of Hsf1S326 contribute to MnO2 NPs-induced hepatic lipotoxicity and mitophagy, which provide new insights into the effects of metal oxides nanoparticles on hepatotoxicity in vertebrates.

Development and validation of an ultra performance liquid chromatography-quadrupole time of flight-mass spectrometry (in MSE mode) method for the quantitative determination of 20 antimicrobial residues in edible muscle tissue of European sea bass.

A UPLC-QTOF-MS method for the simultaneous determination of 20 veterinary drug residues and metabolites (tetracyclines, quinolones, sulfonamides and diaminopyrimidines) in edible muscle plus skin tissue of European sea bass (Dicentrarchus Labrax) was developed. For the identification of analytes a positive electrospray ionization quadropole time-of flight mass spectrometer operating in MSE mode (UPLC-QTOF-MSE) was used. MSE mode provides high chromatographic resolution and accurate mass measurements in both MS and MS/MS modes simultaneously in a single run. Separation was achieved on a UPLC BEH C18 (50 mm × 2.1 mm, 1.7 µm) column in a gradient elution program of 10 min. Examined antibiotics were isolated easily after a simple solid-liquid extraction procedure with acidic acetonitrile (0.1% v/v formic acid) and Na2EDTA 0.1 M. Recovery rates from muscle plus skin tissue ranged from 93.8% to 107.5% for all targeted compounds. The detection limits and the limits of quantification ranged from 2.22 to 15.00 µg/kg, and from 6.67 to 45.46 µg/kg, respectively. The developed method was validated in terms of selectivity, matrix effect, linearity, accuracy, precision, stability and sensitivity, CCα and CCß according to European Union Decision 2002/657/EC. The proposed method was applied for the analysis of contaminated fish samples after in feed administration of danofloxacin mesylate.