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Implication of ferroptosis in hepatic toxicity upon single or combined exposure to polystyrene microplastics and cadmium
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This study found that polystyrene microplastics combined with cadmium caused more severe liver damage in mice than either pollutant alone. The microplastics absorbed cadmium on their surface, increasing the amount of the toxic metal delivered to liver cells, and triggered a type of cell death called ferroptosis. This is concerning because microplastics in the environment commonly carry heavy metals, meaning the combined exposure people face may be more harmful than we thought.
Microplastics (MPs) are a newly emerging type of pollutants. To date, MPs have been found in the atmosphere, soil, water, and even in human samples, posing a non-negligible threat to humans. Furthermore, multiple heavy metals have been found to co-exist with MPs or be absorbed by MPs. This leads to a widespread concern about their combined toxicity, which is currently elusive. Herein, we investigated the single or combined toxic effects of polystyrene MPs (PS-MPs) and cadmium chloride (CdCl) on the liver and hepatocytes. After co-incubation, cadmium (Cd) can be absorbed by PS-MPs, resulting in physiochemical alterations of PS-MPs. In vivo and in vitro experiments revealed that PS-MPs solely or together with CdCl induced ferroptosis in hepatocytes, a newly defined programmed cell death characterized by lipid oxidation and iron accumulation. PS-MPs exerted more ferroptotic effect on hepatocytes than CdCl, and combined exposure to PS-MPs and CdCl enhanced their ferroptotic effect, mainly by stimulating reactive oxygen species (ROS) production and inhibiting antioxidant activity. Upon single or combined exposure to PS-MPs and CdCl, the induction of ferroptosis in hepatocytes can be inhibited by N-acetyl-cysteine (NAC, an ROS scavenger), deferoxamine (DFO, an iron chelator), and particularly ferrostatin-1 (Fer-1, a specific ferroptosis inhibitor). Fer-1 efficiently rescued the cell viability of hepatocytes upon exposure to PS-MPs and CdCl through enhancing the antioxidant system via upregulating GPX4 and SLC7A11. These findings would contribute to an in-depth understanding of the single and combined toxicity of microplastics and cadmium.
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Liver Injury Induced by Exposure to Polystyrene Microplastics Alone or in Combination with Cadmium in Mice Is Mediated by Oxidative Stress and Apoptosis
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Researchers exposed mice to polystyrene microplastics alone and combined with cadmium over eight weeks to study liver damage. Both exposures caused liver injury through oxidative stress and programmed cell death, but the combination of microplastics and cadmium produced more severe effects. The study suggests that microplastics may worsen the toxic impact of heavy metals on the liver when both are present together.
Synergistic effect of PS-MPs and Cd on male reproductive toxicity: Ferroptosis via Keap1-Nrf2 pathway
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A mouse study found that microplastics and the heavy metal cadmium work together to cause more severe damage to male reproductive organs than either pollutant alone. The combination triggered a form of cell death called ferroptosis by disrupting a key protective pathway in the body. This is the first study to show this synergistic reproductive harm, suggesting that microplastics can make other environmental toxins more dangerous.
Co-exposure to environmentally relevant concentrations of cadmium and polystyrene nanoplastics induced oxidative stress, ferroptosis and excessive mitophagy in mice kidney
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A mouse study found that combined exposure to cadmium (a toxic metal) and polystyrene nanoplastics caused more kidney damage than either pollutant alone. The combination triggered a harmful chain reaction involving oxidative stress, iron buildup, and excessive breakdown of cellular energy factories called mitochondria. This is significant because people are often exposed to both nanoplastics and heavy metals simultaneously, and their combined effects may be worse than expected.
Activation of pyroptosis and ferroptosis is involved in the hepatotoxicity induced by polystyrene microplastics in mice
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Researchers exposed mice to polystyrene microplastics and found that the particles caused significant liver damage, including structural changes and impaired function. The study identified two specific cell death pathways, pyroptosis and ferroptosis, as key mechanisms driving the liver injury. These findings suggest that microplastic exposure may harm liver health through multiple biological pathways that warrant further investigation.
Transcriptomic and Metabolomic Analysis Reveals That Polystyrene Microplastics Exacerbate Cadmium-Induced Liver Damage in Mice Associated with AMPK-FOXO-Mediated Energy Metabolism Dysregulation
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A new mouse study found that microplastics can make cadmium (a toxic heavy metal found in some foods and pollution) even more damaging to the liver than cadmium alone—causing worse liver injury, more inflammation, and disrupted energy production inside liver cells. This matters because we're regularly exposed to both microplastics and heavy metals in our environment and food, and this research suggests these pollutants may combine to harm our health in ways that studying them separately wouldn't reveal. While this was done in mice and not humans, it raises important questions about the real-world risks of everyday exposure to multiple pollutants at once.
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