Cadmium (Cd) exposure in adult animals can result in multi-organ damages and gut microbiota disturbance. However, Cd's consequences on health and gut microbiota during adolescence are obscure. In the present study, three-week-old SD rats were exposed to Cd at doses of 0, 0.25, 1, and 4 mg/kg body weight for eight weeks, and the changes of liver, kidney, and ovary function, as well as gut microbiota and its metabolomics profile, were analyzed. After transplantation of fecal bacteria from the 4 mg/kg Cd-treated group into age-matched rats (4 mg/kg-Cd recipients), the organ function and inflammatory reaction were evaluated. The results indicated that Cd perturbed gut microbiota composition, significantly decreased the abundance of Prevotella and Lachnoclostridium but increased Escherichia coli_Shigella. The fecal metabolome profile was altered and was closely correlated with some specific genera. These changes were accompanied by the inflammatory response, dyslipidemia, kidney dysfunction, and abnormal estrogen level. In 4 mg/kg-Cd recipients, the serum triglyceride (TG), lipopolysaccharide (LPS), and inflammatory cytokines were increased with the expressions of IL-1β, IL-6, TNF-α genes up-regulated in liver and kidney. Overall, this study demonstrated that Cd exposure during adolescence could cause disturbance of gut microbiota, dysfunction of liver, kidney, and ovary, which may be correlated with the activation of Cd-induced inflammatory response.

As the most commonly used plasticizer, Di-(2-ethylhexyl)-phthalate (DEHP) exists everywhere in the environment due to the widespread use of polyvinyl chloride (PVC) in human life, and it is also a recognized environmental pollutant. Studies have proved the hepatotoxicity of DEHP, however the mechanism has not been adequately explored, especially the role of the reactive oxygen species (ROS) in it. In the present study, 21 day-old ICR mice were administered DEHP with dose of 0, 125, 250, and 375 mg/kg/day for 28 days by intragastrical gavage. After contamination, histopathology displayed that liver tissue were damaged mildly with the effect of DEHP; a significant increase of the serum liver function index (including aspartate transaminase (AST) and alanine transaminase (ALT)) were observed. Additionally, the level of lipid peroxidation markedly rise, especially ROS and malondialdehyde (MDA), but the activation of superoxide dismutase (SOD) was obviously decreased in mice liver. In addition, DEHP promoted the phosphorylation of JNK and p38MAPK proteins in mice liver, as well as increased the expression of p53 protein and decreased the level of DNA methylation in the p53 gene promoter region. These results indicated that the hepatotoxicity of mice caused by DEHP may be through activating the JNK/p38MAPK/p53 signaling pathway and further promoting the generation of ROS to induce lipid peroxidation in liver, and the role of DNA methylation may be inevitable.