Keap1-Nrf2 pathway up-regulation via hydrogen sulfide mitigates polystyrene microplastics induced-hepatotoxic effects

[Display omitted] •Polystyrene microplastics (mic-PS) accumulated in the liver of mice.•Mic-PS induced inflammation, apoptosis and oxidative stress in mice.•NaHS ameliorated hepatic injury induced by mic-PS exposure.•NaHS reduced micro-Ps-induced hepatic ROS by facilitating nuclear accumulation of Nrf2.•Upregulation of HO-1 and NQO1 involved in positive effects of NaHS. Microplastics, which are new types of environmental pollutants, are recently receiving widespread attention worldwide. Hydrogen sulfide (H2S) as the third endogenous gaseous mediator had protective effects in multiple physiological and pathological conditions. However, the protective role of H2S in microplastics-induced hepatotoxocity remain unclear. In this study, our data showed that H2S significantly suppressed inflammation, apoptosis and oxidative stress induced by polystyrene microplastics (mic-PS) (20 mg/kg b.w.) in the liver. Strikingly, although mic-PS exposure increased the expression of nuclear factor-E2-related factor (Nrf2), it did not influence the levels of heme oxygenase-1 (HO-1) and NAD(P)H: quinone oxidoreductase 1 (NQOl) in the L02 hepatocytes. Immunofluorescence assay showed that sodium hydrosulfide (NaHS) reduced micro-Ps-induced hepatic apoptosis by facilitating nuclear accumulation of Nrf2. Simultaneously, flow cytometry also showed that NaHS could prevent mic-PS-induced accumulation of reactive oxygen species (ROS) by increasing the expression of HO-1 and NQO1. Furthermore, inhibition of HO-1 could reverse the hepatic protective effects of NaHS during mic-PS exposure. Mechanistically, H2S elevating the HO-1 and NQO1 expression by facilitating nuclear accumulation of Nrf2, and consequently reducing mic-PS-induced hepatic apoptosis and inflammation. This study unveils the hepatotoxic effects of MPs and suggest NaHS have protective effects on mic-PS-induced liver damage.