Combined exposure to lead and microplastics increased risk of glucose metabolism in mice via the Nrf2/NF‐κB pathway

Abstract The purpose of this study was to explore the effects of combined lead (Pb) and two types of microplastic (MP) (polyvinyl chloride [PVC] and polyethylene [PE]) exposure on glucose metabolism and investigate the role of the nuclear factor erythroid 2‐related factor 2 (Nrf2)/nuclear factor‐kappa B (NF‐κB) signaling pathway in mediating these effects in mice. Adult C57BL/6J mice were randomly divided into four groups: control, Pb (100 mg/L), MPs (containing 10 mg/L PE and PVC), and Pb + MPs, each of which was treated with drinking water. Treatments were conducted for 6 weeks. Co‐exposure to Pb + MPs exhibited increase glycosylated serum protein levels, insulin resistance, and damaged glucose tolerance compared with the control mice. Additionally, treatment with Pb + MPs caused more severe damage to hepatocytes than when exposed to them alone concomitantly, exposed to Pb + MPs exhibited improved the levels of interleukin‐6, tumor necrosis factor‐alpha, and malondialdehyde, but reduced superoxide dismutase, glutathione peroxidase, and catalase assay in livers. Furthermore, they increase the Kelch‐like ECH‐associated protein 1 (Keap1) and phosphorylated p‐NF‐κB protein levels but reduced the protein levels of heme oxygenase‐1 and Nrf2, as well as increased Keap1 mRNA and Nrf2 mRNA. Co‐exposure to Pb + MP impacts glucose metabolism via the Nrf2 /NF‐κB pathway.