Bisphenol A (BPA) continuously leaches from consumer products and accumulates in the human body, with detectable levels in urine. Emerging evidence suggests potential associations between prolonged BPA exposure and subclinical nephrotoxicity accompanied by metabolic dysregulation, though the gene regulatory mechanisms underlying these associations remain insufficiently characterized. In this study, bioinformatics analyses were employed to systematically reveal the potential transcriptional regulation of chronic renal injury due to BPA exposure. Complementary positron emission tomography/computed tomography (PET/CT) imaging revealed pronounced renal inflammatory responses and localized tissue damage in murine models following 6-week oral BPA administration. Histopathological examination of the kidney revealed exfoliation of renal tubular epithelial cells, with collagen fibers and mucus deposits. Further multi-omics integration (transcriptomic-metabolomic) analysis identified significant perturbations in cortisol biosynthesis, aldosterone regulation, and MAPK signaling cascades induced by BPA exposure. These findings were further validated through molecular docking studies and MAPK inhibitor intervention studies in cellular models. In summary, a critical pathway in BPA-induced renal injury involves the modulation of 11β-hydroxysteroid dehydrogenase type 2 (11β-HSD2) expression, which is mediated by p38 MAPK. This process impacts cortisol metabolism and aldosterone synthesis, suggesting that the biosynthesis of renal steroid hormones is intricately linked to MAPK regulation in renal injury following BPA exposure. Our findings furnish a theoretical foundation for elucidating the mechanisms underlying BPA-induced nephrotoxicity and contribute a holistic viewpoint to environmental health risk assessments.

Ketamine has recently become an anesthetic drug used in human and veterinary clinical medicine for illicit abuse worldwide, but the detection of illicit abuse and inference of time intervals following ketamine abuse are challenging issues in forensic toxicological investigations. Here, we developed methods to estimate time intervals since ketamine use is based on significant metabolite changes in rat serum over time after a single intraperitoneal injection of ketamine, and global metabolomics was quantified by ultra-performance liquid chromatography-quadrupole-time-of-flight mass spectrometry (UPLC-Q-TOF–MS). Thirty-five rats were treated with saline (control) or ketamine at 3 doses (30, 60, and 90 mg/kg), and the serum was collected at 21 time points (0 h to 29 d). Time-dependent rather than dose-dependent features were observed. Thirty-nine potential biomarkers were identified, including ketamine and its metabolites, lipids, serotonin and other molecules, which were used for building a random forest model to estimate time intervals up to 29 days after ketamine treatment. The accuracy of the model was 85.37% in the cross-validation set and 58.33% in the validation set. This study provides further understanding of the time-dependent changes in metabolites induced by ketamine abuse.