F-53B mediated ROS affects uterine development in rats during puberty by inducing apoptosis.

Perfluoroalkyl and polyfluoroalkyl substances (PFASs), as pollutants, can cause palpable environmental and health impacts around the world, as endocrine disruptors, can disrupt endocrine homeostasis and increase the risk of diseases. Chlorinated polyfluoroalkyl ether sulfonate (F-53B), as a substitute for PFAS, was determined to have potential toxicity. Puberty is the stage when sexual organs develop and hormones change dramatically, and abnormal uterine development can increase the risk of uterine lesions and lead to infertility. This study was designed to explore the impact of F-53B on uterine development during puberty. Four-week-old female SD rats were exposed to 0.125 and 6.25 mg/L F-53B during puberty. The results showed that F-53B interfered with growth and sex hormone levels and bound to oestrogen-related receptors, which affected their function, contributed to the accumulation of reactive oxygen species, promoted cell apoptosis and inhibited cell proliferation, ultimately causing uterine dysplasia.

Co-exposure with cadmium elevates the toxicity of microplastics: Trojan horse effect from the perspective of intestinal barrier.

Microplastics (MPs) have been shown to adsorb heavy metals and serve as vehicles for their environmental transport. To date, insufficient studies have focused on enterohepatic injury in mice co-exposed to both MPs and cadmium (Cd). Here, we report that Cd adsorption increased the surface roughness and decreased the monodispersity of PS-MPs. Furthermore, exposure to both PS-MPs and Cd resulted in a more severe toxic effect compared to single exposure, with decreased body weight gain, shortened colon length, and increased colonic and hepatic inflammatory response observed. This can be attributed to an elevated accumulation of Cd resulting from increased gut permeability, coupled with the superimposed effects of oxidative stress. In addition, using 16 S sequencing and fecal microbiota transplantation, it was demonstrated that gut microbiota dysbiosis plays an essential role in the synergistic toxicity induced by PS-MPs and Cd in mice. This study showed that combined exposure to MPs and Cd induced more severe intestinal and liver damage in mice compared to individual exposure, and provided a new perspective for a more systematic risk assessment process related to MPs exposure.

Indole-3-acetamide from gut microbiota activated hepatic AhR and mediated the remission effect of Lactiplantibacillus plantarum P101 on alcoholic liver injury in mice.

Alcoholic liver disease is a prevalent condition resulting from excessive alcohol consumption, characterized by hepatic lipid accumulation and inflammation. This study delved into the protective effects and mechanisms of L. plantarum P101 on alcoholic liver injury in mice. As a result, L. plantarum P101 intervention reduced ALT and AST release, indicative of hepatocyte injury alleviation, while enhancing the activity of the antioxidant enzymes SOD and CAT. A reduction in pro-inflammatory cytokine TNF-α and an increase in anti-inflammatory cytokine IL-10 levels were observed in the L. plantarum P101-intervened mouse liver, signifying reduced inflammation within the mice. Furthermore, L. plantarum P101 intervention altered the gut microbial composition, primarily marked by an increase in Bacteroidota abundance, along with significant enrichment of beneficial bacteria, including Coprostanoligenes, Blautia and Lactiplantibacillus. Correlation analysis unveiled connections between serum tryptophan metabolites and the altered gut microbiota genera, suggesting that gut microbiota-driven effects may extend to extraintestinal organs through their metabolites. Intriguingly, serum indole-3-acetamide (IAM) was elevated by L. plantarum P101-regulated gut microbiota. Subsequently, the role of IAM in ameliorating alcoholic injury was explored using HepG2 cells, where it bolstered cell viability and attenuated EtOH-induced oxidative damage. Concomitantly, IAM activated the gene and protein expression of AhR in cells. Likewise, hepatic AhR expression in mice subjected to L. plantarum P101 significantly up-regulated, possibly instigated by gut microbiota-mediated IAM. Collectively, L. plantarum P101 orchestrates a modulation of gut microbiota and its metabolites, particularly IAM, to activate AhR, thereby alleviating alcoholic liver injury.