Microplastic-induced hepatic adverse effects evaluated in advanced quadruple cell human primary models following three weeks of repeated exposure

Nano and microplastics are defined as particles smaller than 100 nm and 5 mm respectively. The widespread production and use of plastics in everyday life has resulted in significant accumulation of plastic debris in the environment. Over the last two decades there are increased concerns regarding the potential entry and accumulation of plastics in the human body with ingestion being one of the most important routes of exposure. However, the magnitude and nature of potential toxic effects of plastic exposure to human health is not yet fully understood. The liver is the body's principal detoxification organ and critically to this study recognized as the main accumulation site for particulates. In this study as the first of its kind the health impacts of long term low repeated polystyrene microplastics (1 and 5 μm) exposure was investigated in a functionally active 3D liver microtissue model, composed of primary human hepatocytes, Kupffer cells, sinusoidal endothelial cells and hepatic stellate cells. The highlight from the data includes microplastic-induced dose (3.125-25 μg/ml) and time dependent (up to 504 h) increase in cell death and inflammation manifested by enhanced release of IL6, IL8 and TNF-α. The exposure to repeated dosing of the plastics also resulted in notable pathology manifested as aberrant tissue architecture, such as dilated bile canaliculi and large lipid droplets inside the hepatic cells. This toxicity matched extremely well to the accumulation of the materials with the cells of microtissue predominately in the organ macrophages. This study highlights the real issue and danger of microplastic exposure with potential for long-term accumulation and adverse effects of non-biodegradable plastics within the liver.