Exposure to polystyrene nanoplastics impairs lipid metabolism in human and murine macrophages in vitro.

The use of polystyrene micro and nanoplastics in cosmetics and personal care products continues to grow every day. The harmful effects of their biological accumulation in organisms of all trophic levels including humans have been reported by several studies. While we have accumulating evidence on the impact of nanoplastics on different organ systems in humans, only a handful of reports on the impact of polystyrene nanoplastics upon direct contact with the immune system at the cellular level are avialable. The present study offers significant evidence on the cell-specific harmful impact of sulfate-modified nanoplastics (S-NPs) on human macrophages. Here we report that exposure of human macrophages to S-NPs (100 µg/mL) stimulated the accumulation of lipids droplets (LDs) in the cytoplasm resulting in the differentiation of macrophages into foam cells. The observed effect was specific for human and murine macrophages but not for other cell types, especially human keratinocytes, liver, and lung cell models. Furthermore, we found that S-NPs mediated LDs accumulation in human macrophages was accompanied by acute mitochondrial oxidative stress. The accumulated LDs were further delivered and accumulated into lysosomes leading to impaired lysosomal clearance. In conclusion, our study reveals that exposure to polystyrene nanoplastics stabilized with anionic surfactants can be a potent stimulus for dysregulation of lipid metabolism and macrophage foam cell formation, a characteristic feature observed during atherosclerosis posing a serious threat to human health.

The lysosome-mitochondrion crosstalk engaged in silver nanoparticles-disturbed mitochondrial homeostasis.

Given their increasing industrial and biomedical applications, silver nanoparticles (AgNPs) have become widely present in the environment. However, to date, studies on their potential health risks have been far from sufficient, especially those regarding their neurotoxic effects. This study investigated the neurotoxic effects of AgNPs on neural PC-12 cells in the context of mitochondria, which play an important role in AgNP-induced cellular metabolism disturbance and even cell death. Our results show that the endocytosed AgNPs, and not extracellular Ag+, appear to directly determine cell fate. Importantly, endocytosed AgNPs led to mitochondrial swelling and vacuolation without direct interaction. Although mitophagy, a selective autophagy process, was invoked to rescue damaged mitochondria, it failed to function in mitochondrial degradation and recycling. Discovery of the underlying mechanism showed that the endocytosed AgNPs could directly translocate into lysosomes and then cause lysosome perturbation, which is the main factor leading to mitophagy blockade and the subsequent accumulation of defective mitochondria. After lysosomal reacidification via cyclic adenosine monophosphate (cAMP), AgNP-induced dysfunctional autolysosome formation and disturbed mitochondrial homeostasis were reversed. In summary, this study reveals that lysosome-mitochondrion crosstalk is a main mechanism for AgNP-induced neurotoxic effects, offering an inspiring perspective on the neurotoxic effects of AgNPs.

Histological and ultrastructural changes observed in testicles, epididymides, seminal vesicles and liver of rat after intraperitoneal administration of aluminum and indium.

BACKGROUND: Aluminum (Al) and indium (In) have been largely used in medicine, pharmacy, dentistry, manufacturing, engineering, clothing as well as food processing and packaging. Our previous study showed that In was accumulated as electron-dense materials in lysosomes of Sertoli and Leydig testicular cells and the liver ones, when administered to male rats as soluble form. For this reason, we have undertaken to confirm whether Al have the same behavior as In and to enlarge this behavior to other organs of the male reproductive system: epididymis and seminal vesicle. METHODS: Experiments were performed on 24 adult male Wistar rat weighing approximately 250 g. Animals were divided to 3 groups, received Al, In or saline solution as 7 chronic intraperitoneal injections over a period of two weeks and were sacrificed 24 h after the last injection. For ultrastructure study we used The Transmission Electron Microscopy (TEM). RESULTS: The TEM showed the presence of electron-dense granules in lysosomes of testicular cells (Sertoli and Leydig cells), and in the principal epididymal and seminal vesicle cells of Al and In treated rats. Impairments were observed in the endoplasmic reticulum and mitochondria and many vacuoles were identified in the cells cytoplasm. Our results concluded that lysosomes of Leydig and Sertoli cells, principal epididymis, and seminal vesicle cells as well as liver cells, played a central role in the extraction and concentration of Al and In under insoluble form after their introduction into the body as a soluble route. This mechanism intended to protect the organism against exogenous toxic and non-recognized mineral elements after their intrusion into the body. CONCLUSION: It looks important to proceed with the study of Al and In impact on the endocrine and exocrine functions of the male rat reproductive system.

Single-walled carbon nanotubes and graphene oxides induce autophagosome accumulation and lysosome impairment in primarily cultured murine peritoneal macrophages.

The wide application of carbon nanomaterials in various fields urges in-depth understanding of the toxic effects and underlying mechanisms of these materials on biological systems. Cell autophagy was recently recognized as an important lysosome-based pathway of cell death, and autophagosome accumulation has been found to be associated with the exposure of various nanoparticles, but the underlying mechanisms are still uncertain due to the fact that autophagosome accumulation can result from autophagy induction and/or autophagy blockade. In this study, we first evaluated the toxicity of acid-functionalized single-walled carbon nanotubes and graphene oxides, and found that both carbon nanomaterials induced adverse effects in murine peritoneal macrophages, and GOs were more potent than AF-SWCNTs. Both carbon nanomaterials induced autophagosome accumulation and the conversion of LC3-I to LC3-II. However, degradation of the autophagic substrate p62 protein was also inhibited by both nanomaterials. Further analyses on lysosomes revealed that both carbon nanomaterials accumulated in macrophage lysosomes, leading to lysosome membrane destabilization, which indicates reduced autophagic degradation. The effects of AF-SWCNTs and GOs on cell autophagy revealed by this study may shed light on the potential toxic mechanism and suggest caution on their utilization.