The Antibacterial Effect And Murine Toxicity Of ZnO Nanoparteicles

Nanotechnology has been rapidly developed in recent years, a lot of nanoparticles had been used as antibacterial agents in areas of biomedical, food industries, and cosmetics. As an active oxide antibacterial materiala, ZnO nanoparticles(ZnO NPs) have become a hot topic due to its long effectiveness, broad-spectrum antibacterial ability, and non-inducing bacterial resistance.In order to explore antibacterial mechanism of ZnO NPs in complex water matrix containing multiple components, antibacterial activity of ZnO NPs was observed in the presence of organic acids(acetic acid, lactic acid, propionic acid, and isobutyric acid) in comparison with ZnO NPs buffer alone. The results indicated that the dissolutions of the ZnO NPs, the concentration of released Zn2+, and the antibacterial activity were increased in the presence of presence of organic acids. Propidium monoazide(PMA)-PCR and scanning electron microscopy(SEM) were indicated that Zn O NPs with organic acids can cause damage on the cell membrane integrity and cell morphology of both B. cereus and E. coli. The presence of NAC indicated that ROS was not the cause of the ultra-fine-ZnO toxicity to the bacteria tested. The results of these studied indicated that Zn2+ ions played a major role in the microbial toxicity mechanism of ZnO NPs.To explore the toxicity of ZnO NPs in vivo, various sizes of ZnO particles(100 nm, 90 nm, and 30 nm) that were ingested orally over a period of 3 days were evaluated in mice. The blood biochemistry, hematological analyses showed that there was apparent toxicity caused by 30 nm ZnO NPs in mice. Investigation of the liver of mice treated with the 30 nm ZnO NPs showed karyomegaly of hepatocytes, partial disruption of central vein and damage. The RT-qPCR data indicated that 30 nm ZnO NPs can induce significant endoplasmic reticulum(ER) stress responses, and PERK-eIF2?-ATF4-Chop and JNK pathway were activated. In addition, The ER stress marker of caspase-3, caspase-9, caspase-12, and pro-apoptotic protein Bax at the mRNA levels were higher expression in 30 nm ZnO NPs than that in bulk ZnO or in 90 nm ZnO. These findings implied that the smaller ZnO NPs(30 nm) activated ER stress responses that signified severe apoptosis in murine liver.ZnO NPs is slightly soluble which affects its antibacterial property, while the high concentration of ZnO NPs would show adverse effects in vivo. Since enhanced antibacterial activity of ZnO NPs was observed in the presence of organic acids, ZnO NPs was mixed with lactobacillus-fermentation liquor(LFL, with various organic acid produced by the lactobacilli) to enhance the antibacterial effect. The result indicated that ZnO NPs and LFL exhibited synergistic antibacterial activity against Salmonella Typhimurium in vitro. Moreover, qPCR and PCR-DGGE suggested that ZnO NPs and LFL exhibited synergistic antibacterial effect on Enterobacteria and Salmonella in the intestinal tract of mice infected Salmonella, and showed gastrointestinal tract repair capacity.As a conclusion, releasing of Zn2+ was the main antibacterial mechanisms of ZnO NPs, while ZnO NPs would induce liver damage through ERS response. However, the mixture of ZnO NPs and LFL could enhance the antibacterial activity at low ZnO NPs concentration and decreased the toxicity at high concentration. Therefore, this study provides a model for exploitation or development of ZnO NPs.