Effects of zinc oxide nanoparticles on Kupffer cell phagosomal motility, bacterial clearance, and liver function

Abstract

Background Zinc oxide engineered nanoparticles (ZnO ENPs) have potential as nanomedicines due to their inherent properties. Studies have described their pulmonary impact, but less is known about the consequences of ZnO ENP interactions with the liver. This study was designed to describe the effects of ZnO ENPs on the liver and Kupffer cells after intravenous (IV) administration. Materials and methods First, pharmacokinetic studies were conducted to determine the tissue distribution of neutron-activated 65 ZnO ENPs post-IV injection in Wistar Han rats. Then, a noninvasive in vivo method to assess Kupffer cell phagosomal motility was employed using ferromagnetic iron particles and magnetometry. We also examined whether prior IV injection of ZnO ENPs altered Kupffer cell bactericidal activity on circulating Pseudomonas aeruginosa . Serum and liver tissues were collected to assess liver-injury biomarkers and histological changes, respectively. Results We found that the liver was the major site of initial uptake of 65 ZnO ENPs. There was a time-dependent decrease in tissue levels of 65 Zn in all organs examined, refecting particle dissolution. In vivo magnetometry showed a time-dependent and transient reduction in Kupffer cell phagosomal motility. Animals challenged with P . aeruginosa 24 hours post-ZnO ENP injection showed an initial (30 minutes) delay in vascular bacterial clearance. However, by 4 hours, IV-injected bacteria were cleared from the blood, liver, spleen, lungs, and kidneys. Seven days post-ZnO ENP injection, creatine phosphokinase and aspartate aminotransferase levels in serum were significantly increased. Histological evidence of hepatocyte damage and marginated neutrophils were observed in the liver. Conclusion Administration of ZnO ENPs transiently inhibited Kupffer cell phagosomal motility and later induced hepatocyte injury, but did not alter bacterial clearance from the blood or killing in the liver, spleen, lungs, or kidneys. Our data show that diminished Kupffer cell organelle motion correlated with ZnO ENP-induced liver injury.

Histological Changes of MaleWestarRats liver Following the Ingestion of Zinc Oxide Nanoparticles With special Emphasis on the Histochemical Alterations

“…Hexagonal lobules are centered on the central vein that exhibited moderate to severe congestion with the hepatic artery, sinusoids and Portal vein. These investigations are coinciding with Landsiedel et al, [25] and Watson et al, [26] who claimed that the histological analysis of liver sections showed areas of necrosis accompanied by significant inflammatory cell infiltration near the hepatic portal triad at day 7 of exposure. By this time, the engulfed ZnO ENPs would have dissolved, releasing zinc ions, which may have caused toxicity to the surrounding hepatocytes.…”

Controlled synthesis of ZnO nanoparticles and evaluation of their toxicity in Mus musculus mice

“…The results indicate that administration of ZnO-NPs transiently inhibited Kupffer cell phagosomal motility and later induced hepatocyte injury. In addition, the data show that diminished Kupffer cell organelle motion correlated with ZnO-NPs-induced liver injury [62]. This effect would be important to justify the results obtained in our work.…”

“…It is possible that the free radicals generated by the ZnO-NPs [60] cause lipid peroxidation and oxidative stress, inducing steatosis in the liver of the mice, specifically in specimens given ZnO-NP doses, these mice being the ones which presented this disease. In addition, ZnO-NPs could be dissociated in biological media [61] [62]. Alterations in the hepatic ultrastructure in rats have also been reported for nanoparticles of ceria [63].…”

“…This accounts for the results of bioaccumulation of ZnO particles in the liver of the mice used for this test in this work, and even more so for the doses with ZnO-NPs (see Table 3). Specifically, liver macrophages such as Kupffer cells have been identified in some studies as the primary cellular location in the liver for removing nanoparticles [73] and therefore are currently under study to find out more about nanoparticle-liver interaction [62]. The results indicate that administration of ZnO-NPs transiently inhibited Kupffer cell phagosomal motility and later induced hepatocyte injury.…”

Toxicological implications of released particulate matter during thermal decomposition of nano-enabled thermoplastics

“…Importantly, these results also differed greatly from the Fe 2 O 3 nanofiller or comparator material used in the nanocomposite synthesis, which showed no significant biological activity or toxicity in SAEC. We have shown in previous studies that raw iron oxide ENMs are thought to be biocompatible and inert, and hold minimal toxic potential (Watson et al , 2015), which suggests other mechanisms or properties may be influencing the observed toxicity of PE 5% Fe 2 O 3 LCPM exposures.…”