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dcyphr | Tissue accumulation of microplastics in mice and biomarker responses suggest widespread health risks of exposure

Abstract 

    Microplastics (MPs) are of great environmental and health concern. They have been found in oceans, rivers, sediments, sewages, soil, and table salt. This study looks at the effect of MPs on mammalian systems. The tissue distribution, accumulation, and tissue specific health risk of MPs in mice were tested. This study shows that MPs accumulate in the kidneys, liver, and gut. The accumulation is dependent upon the MP’s size. The tissues showed biomarkers that suggested disturbances of energy, lipid metabolism, and oxidative stress. Interestingly, blood markers for neurotoxicity were also altered. This study shows new insights into the potential toxicity from MP exposure. 


Introduction

    MPs are a plastic particle with a diameter less than 5 mm. They can be produced to be this small on purpose. This is what is used in detergent, cosmetics, sunscreens, and as drug delivery systems. The second method of production for MPs is through the mechanical breakdown of larger pieces of plastic. The human population is at risk through direct exposure and exposure by transport up the food chain. Hence, there is the possibility for the accumulation of MPs to cause increased damage as time progresses. 

Previous studies have documented the accumulation  of MPs in aquatic organisms. The results indicate a species specific pattern of accumulation. For instance 8-10 micrometer MPs can be found in crab gill and gut, 10 micrometer MPs can be found in the circulatory system of mussels, and 5 micrometer MPs can accumulate in the liver of zebrafish. Most studies look at the effect of MPs on marine animals, but this study hopes to investigate the accumulation and potential health effects of MPs on mammals. This will act as a better indicator for what the health risk may be for humans. 


Methods 

MPs particles 

Two different plastic types were used. One was a fluorescent polystyrene particle that could glow once excited. This was used to test tissue accumulation and distribution. The other type of particle was used to test for toxicity. Both types of MP tested in this experiment had two sizes: 5 micrometers and 20 micrometers. 


Tissue accumulation of MPs in mice 

75 Mice were randomly assigned to 15 cages. Therefore, 5 mice were placed into 15 cages. One cage was a negative control that did not receive any MP in their diet. Two groupings of 7 cages each received a treatment with the 5 micrometer or 20 micrometer fluorescent microplastic. Then one cage of five mice from each of the 5 micrometer and 20 micrometer groups was sacrificed at 1,2,4,7,14,21, and 28 days after exposure to the MPs. To test retention of MPs after exposure another 10 mice were randomly assigned to two cages with 5 in each. They were exposed to the two different sizes of fluorescent MPs for 28 days. Then, the exposure was terminated one week after 28 days and the mice were sacrificed to collect tissue samples. 


Biological analyses 

To test for toxicity the presence and concentration of certain biomarkers were detected using commercial testing kits. 


Results 

Accumulation and distribution of MPs in mice tissues 

    Both particle sizes were found in the liver, kidney, and gut of the exposed mice. The MP concentration started to taper off around 14 days into exposure. 20 micrometer MPs were highest only in the liver. The 5 micrometer MPs were found in the highest concentration in both the kidney and gut. The concentrations in the kidney and gut were significantly higher than that of the 20 micrometer MPs. However, less than 5 micrometer MPs were retained after exposure were terminated. 


Adverse consequences of MPs in mice 

    No significant changes in food consumption were found between the negative control and MPs exposed group. No differences were seen in final body weight or liver weight between control and treatment groups. However, there was a significant change in liver weight for the high concentration of 5 micrometer MPs group. 


Histological lesions induced by MPs 

Inflammation and lipid droplets were discovered in the mice treated with the plastic meant for toxicology testing. 


Biological variations induced by MPs 

There was a significant decrease in ATP levels and lactate dehydrogenase (LDH) activity. The effects were dependent upon the concentration of microplastic exposed. Lipid metabolism decreased while the amount of oxidative stress increased. Surprisingly, there was no significant differences between biomarkers used between the 5 micrometer and 20 micrometer treatment groups. 


Discussion 

    MPs have been transmitted through the aquatic food chain and into the human diet. Other studies show that MPs have been found in non-marine foods such as salt, sugar, beer, and honey. There is no data exploring if these dietary exposures are enough to cause accumulation in a mammalian system as it does with aquatic species. The results of this study indicate that MPs accumulate in the digestive system, but can also be transported through the circulatory system to other tissues. 

    This study also shows that the relative concentration of certain MPs is dependent upon their size. The 5 micrometer MPs accumulated in greater concentration in the gut than the 20 micrometer MPs. Meanwhile, the 20 micrometer MPs was consistently distributed amongst all tissues. 


Energy metabolism 

Reduced ATP concentration was observed with a sharp increase in lactate dehydrogenase activity in the liver. These two factors are related to energy content of the liver. These results display an energy deficiency in mice, which were confirmed by decreased relative weight of liver despite higher eating. MPs could inhibit the normal absorption of food and reduce digestion.

 

Lipid metabolism 

    Analysis of the liver tissue shows an accumulation of lipid droplets in the liver of mice treated with MPs. Lipid droplets play an important role in lipid storage in liver cells. Their presence is often used to signify inflammatory conditions. 


Oxidative stress 

    Biomarkers that indicate early oxidative stress were discovered. The biomarkers observed are created to reduce the effect of reactive oxygen species (ROS). Otherwise the ROS would cause detrimental effects to the surrounding tissues. The results of this study show that there could be an imbalance in antioxidant defense in the MPs treatment group. 


Neurotoxic responses 

    The levels of specific neurotransmitters were reduced. This indicates a potential neurotoxic response from MP exposure.