Acute exercise in ozone-polluted air induces apoptosis in rat quadriceps femoris muscle cells via mitochondrial pathway.

Ozone (O3) pollution can decrease sport performance and induce respiratory toxicity, but relatively few studies have investigated its effects on skeletal muscles. We randomly assigned rats to the following groups based on a 2 â€‹× â€‹4 two-factor factorial design: Air+0, Air+10, Air+15, and Air+20, O3+0, O3+10, O3+15, and O3+20. The rats in the +0 groups rested, whereas those in the +10, +15, and +20 groups ran on a treadmill (in clean air for Air groups and in air polluted with 0.14 â€‹parts per million [ppm] O3 for O3 groups) at speeds of 10, 15, and 20 â€‹m/min, respectively, for 1 â€‹h. Thereafter, key enzyme activities involving the tricarboxylic acid cycle, oxidative phosphorylation, adenosine triphosphate (ATP) content, histopathological changes, oxidative stress, inflammation factors, and apoptosis were assessed in the rat quadriceps femoris samples. Ozone reduced key enzyme activities and ATP contents in the quadriceps femoris regardless of whether the rats exercised. Pathological changes, inflammatory factors, oxidative stress, and mitochondria-dependent apoptosis were only evident under conditions of exercise combined with ozone and increasingly worsened as exercise intensity increased. These findings suggested that acute exercise under ozone exposure could induce damage to the quadriceps femoris, which would negatively affect sport performance. Ozone-induced disrupted energy metabolism might be an early event that becomes more critical as exercise intensity increases. Therefore, care should be taken when exercising in polluted air, even when ozone pollution is mild.

Ambient ozone exposure induces ROS related-mitophagy and pyroptosis via NLRP3 inflammasome activation in rat lung cells.

OBJECTIVE: To study the regulatory relationship between ozone-induced mitophagy and pyroptosis in lung epithelial cells. RESULTS: First, type I primary alveolar epithelial cells and male Wistar rats were treated with ozone at different dosages. The ATP content and mitochondrial membrane potential significantly decreased in type I primary alveolar epithelial cells. The mitophagy-related markers and PINK1/Parkin pathway-related proteins, and the co-localization of LC3, Parkin, and mitochondria in type I alveolar epithelial cells indicated that ozone exposure triggered mitophagy. On the other hand, the reactive oxygen species (ROS) inhibitor NAC could significantly alleviate mitophagy in epithelial cells. After treatment with the mitophagy inhibitor MDIVI-1, the levels of the NLRP3 inflammasome, cleaved caspase-1, and N-gasdermin D (N-GSDMD) significantly decreased in the cells. Altogether, these results indicated that mitophagy can be triggered by ozone exposure, and subsequently induces cell death mediated by the NLRP3 inflammasome. Finally, the overexpression and knockdown of NLRP3 confirmed this conclusion. CONCLUSION: Ozone exposure induced oxidative damage, leading to mitochondrial structural and functional damage. Ozone-induced ROS triggered mitophagy through the activation of the PINK1/Parkin signaling pathway, then pyroptosis through activation of the NLRP3 inflammasome.

Altered lipidomic profiles in lung and serum of rat after sub-chronic exposure to ozone.

Ozone (O) exposure not only causes lung injury and lung inflammation but also changes blood composition. Previous studies have mainly focused on inflammatory processes and metabolic diseases caused by acute or chronic ozone exposure. However, the effect of ozone on lipid expression profiles remains unclear. This study aimed to investigate the lipidomic changes in lung tissue and serum of rats after ozone exposure for three months and explore the lipid metabolic pathway involved in an ozone-induced injury. Based on the non-targeted lipidomic analysis platform of the UPLC Orbitrap mass spectrometry system, we found that sub-chronic exposure to ozone significantly changed the characteristics of lipid metabolism in lungs and serum of rats. First, the variation in sphingomyelin (SM) and triglyceride (TG) levels in the lung and serum after O3 exposure are shown. SM decreased in both tissues, while TG decreased in the lungs and increased in the serum. Further, the effect of ozone on glycerophospholipids in the lung and serum was completely different. Phosphatidylethanolamine (PE), phosphatidylserine (PS), and phosphatidylinositol (PI) were the major glycerophospholipids whose levels were altered in the lung, while phosphatidylglycerol (PG), phosphatidic acid (PA), and phosphatidylcholine (PC) levels changed dramatically in the serum. Third, after O3 exposure, the level of monogalactosyldiacylglycerol (MGDG), mainly MGDG (43, 11), a saccharolipid, declined significantly and uniquely in the serum. These results suggested that sub-chronic O3 exposure may play a role in the development of several diseases through perturbation of lipidomic profiles in the lungs and blood. In addition, changes in the lipids of the lung and blood may induce or exacerbate respiratory diseases.

Toxic effects of the food additives titanium dioxide and silica on the murine intestinal tract: Mechanisms related to intestinal barrier dysfunction involved by gut microbiota.

This study aimed to compare the effects of three food-grade particles (micro-TiO2, nano-TiO2, and nano-SiO2) on the murine intestinal tract and to investigate their potential mechanisms of action. A 28-day oral exposure murine model was established. Samples of blood, intestinal tissues and colon contents were collected for detection. The results showed that all three particles could cause inflammatory damage to the intestine, with nano-TiO2 showing the strongest effects. Exposure also led to changes in gut microbiota, especially mucus-associated bacteria. Our results suggest that the toxic effects on the intestine were due to reduced intestinal mucus barrier function and an increase in metabolite lipopolysaccharides which activated the expression of inflammatory factors downstream. In mice exposed to nano-TiO2, the intestinal PKC/TLR4/NF-κB signalling pathway was activated. These findings will raise awareness of toxicities associated with the use of food-grade TiO2 and SiO2.

Neurotoxicity and biomarkers of zinc oxide nanoparticles in main functional brain regions and dopaminergic neurons.

Manufactured zinc oxide nanoparticles (Nano-ZnO) are being used increasingly in many fields owing to their excellent physicochemical properties. Consequently, biosecurity has become a growing concern for human health and the environment. In the present study, Nano-ZnO neurotoxicity was investigated in vivo and in vitro. In vivo results showed that Nano-ZnO particles delivered through intranasal instillation were translocated to the brain, specifically deposited in the olfactory bulb, hippocampus, striatum, and cerebral cortex, and caused ultrastructural changes, oxidative damage, inflammatory responses, and histopathological damages there, which may be important for inducing Nano-ZnO neurotoxicity. Further in vitro studies on PC12 cell line illustrated that exposure to Nano-ZnO for 6 h affected cell morphology, decreased cell viability, increased lactate dehydrogenase and oxidative stress activity levels, impaired mitochondrial function, and disturbed the cell cycle. In addition, Nano-ZnO could destroy neuronal structure by affecting cytoskeleton proteins (tubulin-α, tubulin-ß and NF-H), resulting in the interruption of connection between nerve cells, which lead to nervous system function damage. Meanwhile, Nano-ZnO could induce neuronal repair and regeneration disorders by affecting the growth-related protein GAP-43 and delayed neurotoxicity by affecting the calcium/calcium-regulated kinase (CAMK2A/CAMK2B protein) signaling pathway.