Experiments were conducted on mices to study the effect of strain MRe-600 Escherichia coli endotoxin, rifampicin, and their combination at the level of cytochrome p-450, b5, aminopyrine N-demethylase and aniline-r-hydroxylase activity in the liver, absorptive activity and oxygen dependent metabolism of macrophages, and free-radical processes in the liver. It was found that rifampicin removes the endotoxin-induced depression of microsomal oxidation in the liver, but potentiates the stimulating effect of the endotoxin on macrophageal absorptive activity and the "respiratory outburst" in these cells. The oxidative equilibrium in the liver in this case does not change.
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Arch Toxicol
January 2025
School of Chemistry and Chemical Engineering, Guangxi University, Nanning, Guangxi, 530004, People's Republic of China.
Over the past decade, fentanyl-type new psychoactive substances (F-NPS) have emerged as the most representative synthetic opioids in third-generation drugs. These substances are characterized by their "low" fatal dose and parent drug levels in biological matrices, "fast" rates of derivatization and metabolism, and "many" derivatization sites and analogs. The low levels of parent fentanyl NPS in biological matrices complicate their detection, necessitating the use of characteristic metabolites as biomarkers for forensic analysis.
View Article and Find Full Text PDFJ Agric Food Chem
January 2025
Key Laboratory of Entomology and Pest Control Engineering, College of Plant Protection, Southwest University, Chongqing 400715, China.
This study systemically investigated the enantioselective bioaccumulation and degradation of etoxazole (ETZ) in earthworms along with the transcriptome and oxidative stress responses to ETZ enantiomer exposure. Based on the M-shaped bioaccumulation trends for ETZ enantiomers, -ETZ was found to be preferentially bioaccumulated in earthworms. Sublethal toxicity analysis showed that -ETZ induced greater changes in protein content, malondialdehyde content, detoxifying metabolic enzyme activity, and oxidative stress in earthworms, compared to those induced by -ETZ.
View Article and Find Full Text PDFPLoS One
December 2024
Therapeutic Development Branch, Division of Preclinical Innovation, National Center for Advancing Translational Sciences, National Institute of Health, Rockville, Maryland, United States of America.
R-VK4-116 is currently being developed as a medication to treat opioid use disorder (OUD). To characterize in vitro safety properties of R-VK4-116, metabolic stability in hepatocytes or liver microsomes, metabolite identification, metabolism/transporter-mediated drug interactions, lysosomal perturbation, mitochondrial toxicity, off-target enzyme effects, cellular and nuclear receptor functional assays, electrophysiological assays, CiPA, KINOMEscanTM, plasma protein binding, phospholipidosis and steatosis assays were performed. Overall, R-VK4-116 was metabolically stable in hepatocytes and microsomes.
View Article and Find Full Text PDFJ Pharm Biomed Anal
December 2024
Department of Natural Medicine and Pharmacognosy, School of Pharmacy, Qingdao University, Qingdao 266021, PR China. Electronic address:
Higenamine (HG), a naturally occurring benzyltetrahydroisoquinoline alkaloid, has been revealed a variety of biological activities and is extensively utilized in dietary supplements. Currently, HG is under investigation in phase I clinical trials, however, the liver metabolism of HG has so far not been fully elucidated. The present study aimed to identify reactive metabolites of HG using ultrahigh-performance liquid chromatography-tandem mass spectrometry.
View Article and Find Full Text PDFClin Transl Sci
December 2024
Division of Pharmacotherapy and Experimental Therapeutics, University of North Carolina at Chapel Hill Eshelman School of Pharmacy, Chapel Hill, North Carolina, USA.
Venetoclax is a first-in-class orally administered B-cell lymphoma-2 inhibitor used to treat chronic lymphocytic leukemia (CLL). Venetoclax is primarily metabolized in the liver by cytochrome P450 (CYP) 3A4 to its major metabolite M27, via M5, and M2, M3, and M4 via oxidation. Although venetoclax is a breakthrough in CLL treatment, managing drug safety and toxicity remains a clinical challenge.
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