Monoammonium Glycyrrhizinate/Glycine/Cysteine Hydrochloride

Bisphenol P (BPP) has been detected in human biological samples; however studies on its nephrotoxicity are scarce. Given the susceptibility of kidneys to endocrine-disrupting chemicals, there is an urgent need to investigate the renal toxicity of BPP. This study aimed to evaluate the effects of different concentrations of BPPs on the kidneys of C57BL/6 mice and elucidate the underlying mechanisms of renal damage using a combination of mouse renal transcriptomic data and human renal proximal tubular epithelial cells (HK-2). Mice were exposed to BPP (0, 0.3, 30, 3000 μg/kg bw/d) via gavage for 5 weeks. Renal injury was assessed based on changes in body and kidney weights, serum renal function indices, and histopathological examination. Transcriptomic analysis identified differentially expressed genes and pathways, whereas cellular assays were used to measure cell viability, reactive oxygen species (ROS), apoptosis, and the expression of key genes and proteins. The results show that BPP exposure induces renal injury, as evidenced by increased body weight, abnormal renal function indices, and renal tissue damage. Transcriptomic analysis revealed alterations in genes and pathways related to oxidative stress, p53 signaling, autophagy, and apoptosis. Cellular experiments confirmed that BPP induces oxidative stress and apoptosis. Furthermore, BPP exposure significantly inhibits autophagy, potentially exacerbating apoptosis and contributing to kidney injury. Treatment with a ROS inhibitor (N-Acetylcysteine, NAC) mitigated BPP-induced autophagy inhibition and apoptosis, implicating oxidative stress as a key factor. BPP exposure may lead to renal injury through excessive ROS accumulation, oxidative stress, inflammatory responses, autophagy inhibition, and increased apoptosis. The effects of NAC highlight the role of oxidative stress in BPP-induced nephrotoxicity. These findings enhance our understanding of BPP-induced nephrotoxicity and underscore the need to control BPP exposure to prevent renal disease. This study emphasized the importance of evaluating the safety of new Bisphenol A analogs, including BPP, in environmental toxicology.

To compensate for drug response variability, drug metabolism phenotypes are determined based on the results of genetic testing, and if necessary, drug dosages are adjusted. In some cases, discrepancies between predicted and observed phenotypes (phenoconversion) may occur due to drug–drug interactions caused by concomitant medications. We conducted a prospective, exploratory study to evaluate the risk of CYP2C19 phenoconversion in genotyped healthy volunteers exposed to CYP2C19 inhibitors. Three groups of volunteers were enrolled: CYP2C19 g‐RM, g‐NM, and g‐IM (g‐ for genetically predicted). All volunteers received as CYP2C19 phenotyping substrate 10 mg omeprazole (OME) alone at the control session and in co‐administration with CYP2C19 inhibitors: voriconazole 400 mg and fluvoxamine 50 mg in second and third study sessions, respectively. Phenoconversion occurred in over 80% of healthy volunteers, with variations among genotypic groups, revealing distinct proportions in response to fluvoxamine and voriconazole. Statistically significant differences were observed in mean metabolic ratios between CYP2C19 intermediate metabolizers (g‐IMs) with *1/*2 and *2/*17 genotypes, with the *2/*17 group exhibiting lower ratios, and distinctions were noted between genotypic groups, emphasizing the impact of genetic variations on drug metabolism. When reclassified according to CYP2C19 baseline‐measured phenotype into p‐RM, p‐NM, and p‐IM (p‐ for measured phenotype), we observed 100% phenoconversion of p‐RMs and a significant phenotype switch in p‐NMs, p‐IMs, and p‐PMs after fluvoxamine and voriconazole, and complete phenoconversion of p‐IMs to p‐PMs on both inhibitors, emphasizing the impact of genetic variations on the vulnerability to CYP2C19 phenoconversion and the importance of considering both genotyping and phenotyping in predicting drug response.