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

• 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 (H 2 S) as the third endogenous gaseous mediator had protective effects in multiple physiological and pathological conditions. However, the protective role of H 2 S in microplastics-induced hepatotoxocity remain unclear. In this study, our data showed that H 2 S 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, H 2 S 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. [ABSTRACT FROM AUTHOR]