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1.
Biomed Chromatogr ; 38(6): e5859, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38618996

ABSTRACT

The clinical effectiveness of nux-vomica in treating rheumatism and arthralgia is noteworthy; however, its nephrotoxicity has sparked global concerns. Hence, there is value in conducting studies on detoxification methods based on traditional Chinese medicine compatibility theory. Blood biochemistry, enzyme-linked immunosorbent assay, and pathological sections were used to evaluate both the nephrotoxicity of nux-vomica and the efficacy of the Jian Pi Tong Luo (JPTL) compound in mitigating this toxicity. Kidney metabolomics, using ultra-high-performance liquid chromatography-quadrupole-time-of-flight-MS (UPLC-Q-TOF-MS), was applied to elucidate the alterations in small-molecule metabolites in vivo. In addition, network pharmacology analysis was used to verify the mechanism and pathways underlying the nephrotoxicity associated with nux-vomica. Finally, essential targets were validated through molecular docking and western blotting. The findings indicated significant nephrotoxicity associated with nux-vomica, while the JPTL compound demonstrated the ability to alleviate this toxicity. The mechanism potentially involves nux-vomica activating the "PTGS2/CYP2C9-phosphatidylcholine-arachidonic acid metabolic pathway." This study establishes a scientific foundation for the clinical use of nux-vomica and lays groundwork for further research and safety assessment of toxic Chinese herbal medicines.


Subject(s)
Arachidonic Acid , Cyclooxygenase 2 , Drugs, Chinese Herbal , Kidney , Animals , Drugs, Chinese Herbal/pharmacology , Drugs, Chinese Herbal/chemistry , Kidney/drug effects , Kidney/metabolism , Arachidonic Acid/metabolism , Male , Cyclooxygenase 2/metabolism , Molecular Docking Simulation , Cytochrome P-450 CYP2C9/metabolism , Cytochrome P-450 CYP2C9/genetics , Chromatography, High Pressure Liquid/methods , Rats, Sprague-Dawley , Rats , Metabolomics/methods , Mice
2.
Sci Total Environ ; 822: 153622, 2022 May 20.
Article in English | MEDLINE | ID: mdl-35124035

ABSTRACT

Given the decline of freshwater resources in recent years, the accessible space for freshwater aquaculture is rapidly shrinking, and aquaculture in saline-alkaline water has become a critical approach to meet the rising demand. However, the molecular mechanism behind the adverse effects of saline-alkaline water on fish and the regulatory mechanism in fish tolerance remains unclear. Here, adult crucian carp (Carassius auratus) were exposed to 60 mmol/L NaHCO3 for 30 days. It was observed that long-term carbonate alkalinity (CA) exposure not only caused gill oxidative stress but also changed the levels of several physiological parameters associated with ammonia transport, including blood ammonia, urea nitrogen (BUN), glutamine (Gln), and glutamine synthetase (GS). According to the metabolomics study, differential metabolites (DMs) engaged in various metabolic pathways, such as glycerophospholipid metabolism, sphingolipid metabolism, and arachidonic acid metabolism. In addition, transcriptomics data showed that differentially expressed genes (DEGs) were closely related to ammonia transport, apoptosis, and immunological response. In general, comprehensive multi-omics and biochemical analysis revealed that crucian carp might adopt Rh glycoprotein as a carrier to mediate ammonia transport and increase glutamine and urea synthesis under long-term high saline-alkaline stress to mitigate the adverse effects of blocked ammonia excretion. Simultaneously, saline-alkaline stress caused the destruction of the antioxidant system and the disorder of lipid metabolism in the crucian carp gills, which induced apoptosis and immunological response. To our knowledge, this is the first study to investigate fish's molecular and metabolic mechanisms under saline-alkaline stress using integrated metabolomics, transcriptomics, and biochemical assays. Overall, the results of this study provided new insights into the molecular mechanism behind the adverse effects of saline-alkaline water on fish and the regulatory mechanism in fish tolerance.


Subject(s)
Carps , Ammonia/metabolism , Ammonia/toxicity , Animals , Fresh Water/chemistry , Gills/metabolism , Goldfish/metabolism
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