Bisphenol A (BPA) is a globally utilized industrial chemical and is commonly used as a monomer of polycarbonate plastics and epoxy resins. Recent research reveals that BPA could cause potential adverse biological effects and liver dysfunction. However, the underlying mechanisms of BPA-induced hepatoxicity and gut dysbiosis remain unclear and deserve further study. In this study, male Sprague Dawley rats were exposed to different doses (0, 30, 90, and 270 mg/kg bw) of BPA by gavage for 30 days. The results showed that the high dose of BPA decreased superoxide dismutase (SOD), glutathione (GSH), and increased malondialdehyde (MDA) levels. Moreover, a high dose of BPA caused a significant increase in serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), total cholesterol (TC), and low-density lipoprotein cholesterol (LDL-C), while high-density lipoprotein cholesterol (HDL-C) was significantly decreased in BPA-treated rats. The gene expression of PGC-1α and Nrf1 were decreased in the liver of high doses of BPA-administrated rats, as well as the protein levels of SIRT1, PGC-1α, Nrf2, and TFAM. However, the protein expression of IL-1β was significantly increased in BPA-treated rats. In addition, BPA weakened the mitochondrial function of hepatocytes and promoted cell apoptosis in the liver by up-regulating the protein levels of Bax, cleaved-Caspase3, and cleaved-PARP1 while down-regulating the Bcl-2 in the liver. More importantly, a high dose of BPA caused a dramatic change in microbiota structure, as characterized at the genus level by increasing the ratio of Firmicutes to Bacteroidetes (F/B), and the relative abundance of Proteobacteria in feces, while decreasing the relative abundance of Prevotella_9 and Ruminococcaceae_UCG-014, which is positively correlated with the content of short-chain fatty acids (SCFAs). In summary, our data indicated that BPA exposure caused hepatoxicity through apoptosis and the SIRT1/PGC-1α pathway. BPA-induced intestinal flora and SCFA changes may be associated with hepatic damage. The results of this study provide a new sight for the understanding of BPA-induced hepatoxicity.

Environmental di(2-Ethylhexyl) phthalate (DEHP) is widely used in various industries as a plasticizer, and has been reported to induce reproductive and developmental toxicities in organisms. The purpose of this study was to evaluate the detoxification capacity of Lycium barbarum polysaccharides (LBP) and wolfberry juice (WJ) against DEHP-induced hepatotoxicity. Two groups of rats were purchased to study two different intervention method experiments: LBP (50, 100, 200 mg/kg·bw) intervention before DEHP (2000 mg/kg·bw) exposure, and LBP (200 mg/kg·bw) or WJ (8 mL/kg·bw) intervention after DEHP (3000 mg/kg·bw) exposure. The rats were exposed to DEHP once, while the intervention lasted for seven days. At the end of the intervention, enzyme-linked immunosorbent assay (ELISA) was used to measure the related index. The LBP intervention before DEHP exposure experiment (the first experimental method) found that LBP group rats showed a strong capacity toward DEHP detoxification, evidenced by the significant upregulation of activities and concentrations of the partner retinoid, X receptor alpha (RXRα), and downstream regulators Cytochrome P4502E1 (CYP2E1), Cytochrome P4503A1 (CYP3A1), Glutathione S-Transferase Pi (GSTpi), and UDP-glucuronosyltransferase 1 (UGT1) in a dose-dependent manner. The LBP and WJ intervention after DEHP exposure experiment (the second intervention experiment) found that WJ could downregulate pregnane X receptor (PXR), and upregulate downstream regulators, CYP2E1, CYP3A1, and Glutathione S-Transferase (GST) with the extension of intervention time, to alleviate the toxicity of DEHP. However, the intervention effect of WJ was more obvious than that of LBP. These results suggested that LBP and WJ might be effective detoxification agents against DEHP-induced toxic effects, by activating PXR and PXR-related detoxifying enzymes.

Cadmium (Cd) is a frequent environmental pollutant associated with biological toxicity that can harm female reproduction. Anthocyanins have been reported to reduce the toxicity of Cd. In the present study, the protective effects and underlying mechanisms of malvidin-3-O-glucoside (M3G) against the toxicity of Cd on female reproduction in KGN cells (human ovarian granulosa-like tumor cells) were investigated. After treating cells with 10 µmol/L cadmium chloride, the results showed that M3G lessened Cd-induced KGN cell cytotoxicity better than malvidin and malvidin-3,5-O-diglucoside. Additionally, M3G significantly decreased the Cd-induced generation of reactive oxygen species, inhibited the Cd-induced arrest of the G2/M phase of the cell cycle, and increased estradiol (E2) production. According to transcriptomic results, M3G reduced the abnormal expression of genes that responded to estrogen. Additionally, M3G promoted the endogenous synthesis and secretion of E2 by controlling the expression of CYP17A1 and HSD17B7. The current findings indicated that M3G is of great potential to prevent Cd-induced female reproductive impairment as a dietary supplement.

Patulin, an emerging mycotoxin with high toxicity, poses great risks to public health. Considering the poor antibody production in patulin immunization, this study focuses on the four-dimensional data-independent acquisition (4D-DIA) quantitative proteomics to reveal the immune response of patulin in rabbits. The rabbit immunization was performed with the complete developed antigens of patulin, followed by the identification of the immune serum. A total of 554 differential proteins, including 292 up-regulated proteins and 262 down-regulated proteins, were screened; the differential proteins were annotated; and functional enrichment analysis was performed. The differential proteins were associated with the pathways of metabolism, gene information processing, environmental information processing, cellular processes, and organismal systems. The functional enrichment analysis indicated that the immunization procedures mostly resulted in the regulation of biochemical metabolic and signal transduction pathways, including the biosynthesis of amino acid (glycine, serine, and threonine), ascorbate, and aldarate metabolism; fatty acid degradation; and antigen processing and presentation. The 14 key proteins with high connectivity included G1U9T1, B6V9S9, G1SCN8, G1TMS5, G1U9U0, A0A0G2JH20, G1SR03, A0A5F9DAT4, G1SSA2, G1SZ14, G1T670, P30947, P29694, and A0A5F9C804, which were obtained by the analysis of protein–protein interaction networks. This study could provide potential directions for protein interaction and antibody production for food hazards in animal immunization.