Chronic oral exposure to cadmium causes liver inflammation by NLRP3 inflammasome activation in pubertal mice

Cadmium (Cd) is a potentially toxic trace element frequently existed in foods, water, and air, threatening liver function from its continuous bioaccumulation and induction of oxidative stress and inflammation. However, the hepatotoxicity of Cd during puberty remains unclear. In this study, pubertal mice were given cadmium chloride at a dose of 5.0 mg/kg·bw by gavage, and the liver damage was investigated at different treatment points of 10, 20, and 30 days. After Cd exposure, there is an obvious inflammatory hepatocyte infiltration accompanied by more apoptotic cells at 20 days and an increase in alanine aminotransferases and aspartate aminotransferases in circulation at 30 days. Additionally, the soaring TNF-α and MCP-1 were found in liver, and the mRNA expression of pro-inflammatory cytokines (IL-1α, IL-1β, and IL-18) and anti-inflammatory cytokines (TGF-β, IL-10, and IL-13) were both significantly upregulated. Moreover, the activated M1 and M2 macrophages were confirmed in charge of these cytokines release. Most importantly, the data validated a pivotal role of NOD-like receptor pyrin domain containing 3 (NLRP3) inflammasome in Cd-induced inflammation in liver at puberty. Collectively, our results suggested that low-dose Cd oral exposure can cause liver inflammation via activation of NLRP3 inflammasome and give rise to severe liver injury at puberty. [Display omitted] •Chronic exposure to Cd caused hepatocyte inflammatory infiltration at puberty.•Cd increased both pro-inflammatory and anti-inflammatory cytokines in liver at puberty.•Cd can activate both M1 and M2 macrophages in liver at puberty.•NLRP3 inflammasome is responsible for Cd-induced inflammation in liver at puberty.