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Cu-Doped-ZnO Nanocrystals Induce Hepatocyte Autophagy by Oxidative Stress Pathway.

ABSTRACT: As a novel nanomaterial for cancer therapy and antibacterial agent, Cu-doped-ZnO nanocrystals (CZON) has aroused concern recently, but the toxicity of CZON has received little attention. Results of hematology analysis and blood biochemical assay showed that a 50 mg/kg dosage induced the increase in white blood cells count and that the concentration of alanine aminotransferase (ALT), superoxide dismutase (SOD), catalase (CAT), and Malonaldehyde (MDA) in the serum, liver, and lungs of the CZON group varied significantly from the control mice. Histopathological examinations results showed inflammation and congestion in the liver and lung after a single injection of CZON at 50 mg/kg. A transmission electron microscope (TEM) result manifested the autolysosome of hepatocyte of mice which received CZON at 50 mg/kg. The significant increase in LC3-II and decrease in p62 of hepatocyte in vivo could be seen in Western blot. These results indicated that CZON had the ability to induce autophagy of hepatocyte. The further researches of mechanism of autophagy revealed that CZON could produce hydroxyl radicals measured by erythrocyte sedimentation rate (ESR). The result of bio-distribution of CZON in vivo, investigated by ICP-OES, indicated that CZON mainly accumulated in the liver and two spleen organs. These results suggested that CZON can induce dose-dependent toxicity and autophagy by inducing oxidative stress in major organs. In summary, we investigated the acute toxicity and biological distribution after the intravenous administration of CZON. The results of body weight, histomorphology, hematology, and blood biochemical tests showed that CZON had a dose-dependent effect on the health of mice after a single injection. These results indicated that CZON could induce oxidative damage of the liver and lung by producing hydroxyl radicals at the higher dose.

SUBMITTER: Bai Q

PROVIDER: S-EPMC8399041 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:The synthesis of optoelectrically enhanced nanomaterials should be continuously improved by employing time- and energy-saving techniques. The porous zinc oxide (ZnO) and copper-doped ZnO nanocomposites (NCs) were synthesized by the time- and energy-efficient solution combustion synthesis (SCS) approach. In this SCS approach, once the precursor-surfactant complex ignition point is reached, the reaction starts and ends within a short time without the need for any external energy. The TGA-DTA analysis confirmed that 500 °C was the point at which stable metal oxide was obtained. The doping and heterojunction strategy improved the optoelectric properties of the NCs more than the individual constituents, which then enhanced the materials' charge transfer and optical absorption capabilities. The porosity, nanoscale crystallite size (15-50 nm), and formation of Cu/CuO-ZnO NCs materials were confirmed from the XRD, SEM, and TEM/HRTEM analyses. The obtained d-spacing values of 0.275 and 0.234 nm confirm the formation of ZnO and CuO crystals, respectively. The decrease in photoluminescence intensity for the doped NCs corroborates a reduction in electron-hole recombination. On the Mott-Schottky analysis, the positive slope for ZnO confirms the n-type character, while the negative and positive slopes of the NCs confirm the p- and n-type characters, respectively. A diffusion-controlled type of charge transfer process on the electrode surface was confirmed from the cyclic voltammetric analysis. Thus, the overall analysis shows the applicability of the less expensive and more efficient SCS for several applications, such as catalysis and sensors. To confirm this, an organic catalytic reduction reaction of 4-nitrophenol to 4-aminophenol was tested. Within three and a half minutes, the catalytic reduction result showed the great potential of NCs over ZnO NPs. Thus, the energy- and time-saving SCS approach has a great future outlook as an industrial pollutant catalytic reduction application.

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Cu-Doped-ZnO Nanocrystals Induce Hepatocyte Autophagy by Oxidative Stress Pathway.

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