Polystyrene microplastics exposure aggravates acute liver injury by promoting Kupffer cell pyroptosis

To investigate the long-term effects of polystyrene (PS) exposure on acute liver injury. The carbon tetrachloride-induced acute injury mouse model was subjected to long-term PS exposure. Pyroptosis was inhibited by knocking out Gsdmd in mice or treating with the Gsdmd inhibitor necrosulfonamide (NSA) to evaluate the effect of PS on liver injury. Kupffer cells were used as a cellular model to examine the effects of PS on cell pyroptosis, lactate dehydrogenase release rate, structural integrity (propidium iodide staining), and inflammatory factor levels. In mice, PS exposure exacerbated acute liver injury, which was mitigated upon Gsdmd knockout (KO) or NSA treatment along with the downregulation of tissue inflammatory response. In vitro studies demonstrated that PS promoted Kupffer cell pyroptosis, which was suppressed upon Gsdmd KO or NSA treatment along with the alleviation of inflammation. These results suggest that long-term PS exposure exacerbates acute liver injury by promoting Kupffer cell pyroptosis, which is one of the hepatotoxic mechanisms of PS.