The Toxic Effects And Mechanisms Of Micro- And Nano-Plastics On The Intestine

In recent years,the health risks of micro-and nano-plastics have attracted increasing attention,and some previous studies have found that they may pose potential health risks to the human intestine.The intestinal tract plays a very important role in protecting human health.Intestinal epithelium and a variety of immune cells including macrophages on the surface of intestinal epithelium and the mucus secreted by them constitute the physical barrier and immune barrier of the intestine,respectively.The pathways and mechanisms of intestinal toxicity caused by micro-plastics and nano-plastics are crucial to clarify the intestinal health risks of micro-and nano-plastics.At present,most studies focus on the toxic effects of microand nano-plastics on the intestine using animal experiments,and the research on the pathways of toxic effects and their toxicological mechanisms is not comprehensive and systematic enough.Based on the progress and shortcomings of current research,this study investigated whether micro-and nano-plastics pose a threat to intestinal health by destroying the physical and/or immune barriers of the intestine.Both in vivo animal models and in vitro cell models were used to study the intestinal toxicity of micro-and nano-plastics.It mainly includes the following four aspects:(1)The damage of micro-and nano-plastics to organs of mice was studied.The PS microspheres with sizes of 3 μm and 80 nm were used as the model of micro-plastics and nano-plastics,respectively.The results showed that micro-and nano-plastics had obvious damage to the colon tissue of mice.Compared with microplastics,nano-plastics had more obvious damage to the intestinal tissue of mice.Histological damage was observed in kidney,liver,spleen,lung and heart of mice exposed to microplastics and nano-plastics were no obvious.(2)The toxic effects of micro-and nano-plastics on the intestinal physical barrier of mice and the possible toxicological mechanism were explored.Mouse colon cancer cell line CT26.WT was used as a model of intestinal epithelial cells,PS-MP with particle size of 3 μm was used as a model of micro-plastics,PS-NPs with particle size of 80 nm and 20 nm were used as a model of nano-plastics.The results showed that micro-plastics and nano-plastics reduced cell viability in a size-dependent manner.Apoptosis was the main mode of cell death induced by micro/nano-plastics in CT26.WT cells.When n-acetyl-L-cysteine(NAC)as an antioxidant was employed,the cytotoxic induced by PS-M/NPs were attenuated.The value of hazard quotient(HQ)showed that the risk of harm to the intestine far exceeds the margin of safety with reported PS-M/NPs concentrations from dietary exposure.The study highlights the potential risks of micro-and nano-plastics to the intestinal physical barrier.(3)The risk of micro-and nano-plastics ingesting on human intestinal health was studied,and explored a measure to reduce the toxicity of micro/nano-plastics on human intestine.Using human colon carcinoma cells Caco-2 as a human intestinal in vitro model.By examining the effects of the four PS plastic particles with different sizes on cell viability and cell apoptosis,we found that micro-plastics and nano-plastics exhibited cytotoxicity in a sizedependent manner(with cytotoxicity in the range of 3 μm < 0.3 μm < 80 nm < 20 nm).Additionally,we identified oxidative stress as a possible mechanism of cytotoxicity.Furthermore,we found catechins in green tea significantly reduced micro/nano-plasticsinduced cytotoxicity in human intestinal cells.HQ value was calculated based on the reported levels of microplastics in tea made from plastic teabags and human whole blood.The results showed that the harm of human current exposure level of microplastics to human intestinal physical barrier is far beyond the safety margin,highlighting the potential health risks of daily intake and human current exposure level of micro-and nano-plastics to intestinal health.(4)The effects of micro/nano-plastics on the immune barrier function and the possible toxicological mechanism were explored.Using mouse macrophages RAW264.7 cells as in vitro model,The PS microspheres with sizes of 3 μm and 80 nm were used as the model of micro-plastics and nano-plastics,respectively.The results of proteomic analysis showed that the effects of micro-and nano-plastics on macrophage included biological processes,cellular components and molecular functions.And micro-and nano-plastics might be significant interfered with pathways related to inflammatory responses.Micro-and nano-plastics have toxic effects on macrophages by inducing apoptosis,and the possible mechanism is inducing oxidative stress in cells.Micro/nano-plastics induced pro-inflammatory effects by polarizing macrophages into M1.In addition,we found that nano-plastics had a greater adverse effect on macrophages than micro-plastics.Impaired function of macrophages may affect their regulatory function in the immune response,leading to the occurrence and development of inflammation in the body,which may lead to or aggravate other diseases related to intestinal inflammationThis study clarified that the harmful pathway of micro/nano plastics on intestinal health was by destroying the physical and immune barriers of the intestine,explored the toxicological mechanism of the toxic effect of micro-and nano-plastics on intestinal health,and provided a feasible protective measure for reducing the intestinal toxicity of micro-and nano-plastics.This study provides a scientific basis and theoretical basis for the potential risks of micro-and nano-plastics on human intestinal health.