**6.5 Effects on the liver and lipid metabolism**

As mentioned above, when responding to oral exposure to MP and NP, multiple groups showed that the gut microbiota is altered, as well as serum and hepatic markers of amino acid and lipid synthesis and metabolism, as well as liver inflammation [38, 83, 127]. Exposure to these particles produces hepatocellular edema and infiltration of inflammatory cells with increased production of IL-1β and TNF-α; hepatotoxic injury also occurs, whose elevation of serum markers of liver function depends on concentration, exposure time, and particle size; mice exposed to 250 nm Polyurethane (PUR) particles for 10 days showed elevated serum levels of alanine transferase (ALT), alkaline phosphatase (ALP), IL-6, and TNF-α, hepatic vascular congestion, and hepatocyte vacuolization [152]. Subsequently, the exposure was brought about with a mixture of PS particles of 1.4 and 10 μm by the oral probe in triple transgenic reporter mice (HOTT) with heme oxygenase-1 (HO-1), which expressed a LacZ indicator sensitive to oxidative stress and pro-inflammatory processes.

Effects that depend on the concentration of particles [122]. The liver is the main site where lipid metabolism occurs; it is sensitive to pathologies such as NASH, which manifests as an accumulation of fatty vesicles combined with cholesterol and high-circulation triglycerides. The MP and NP alter these performances in rodents. Hepatic distension increased hepatic triglycerides, total cholesterol,

and decreased expression of peroxisome proliferator-activated receptor alpha (PPARα) and peroxisome proliferator-activated receptor gamma (PPARɣ) has been observed. The lipid-sensitive nuclear receptor PPARα regulates catabolism and fatty acid elimination, and some studies concluded that it may have anti-inflammatory effects by suppressing the nuclear factor-kappa B (NF-κB) [153, 154]. Thus, the regulation of PPARα is reduced, predicting the potential development of NASH. It is understood that changes in lipid metabolism depend on particle size, as mentioned above.
