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[Lipid metabolism study of sodium norcantharidate in LO2 hepatocytes based on lipidomics]
Li-Juan Zhao1, Nan Si1, Bo Gao2
1Institute of Chinese Materia Medica,China Academy of Chinese Medical Sciences Beijing 100700,China.
Abstract:
In order to find the endogenous potential biomarkers of in vitro hepatic injury caused by NCTD-Na and elucidate the mechanism of hepatic injury of NCTD-Na,ultra-high performance liquid chromatography coupled quadrupole time-of-flight mass spectrometry(UPLC-Q-TOF-MS/MS) was used for lipidomics detection.Multivariate statistical analysis was used to study the endogenous lipid metabolic changes of human normal liver cells LO2 injury after the treatment with sodium norcantharidate(NCTD-Na).The results showed that the half maximal inhibitory concentration(IC50) of NCTD-Na was 0.034 mmol·L-1.A total of 280 differential metabolites were found between the control group and the low-dose group,with VIP > 2.0 and P<0.05.At the same time,a total of 273 differential metabolites were found between the control group and the high-dose group,with VIP > 2.0 and P<0.05.Cell metabolite profiles showed clear separation among control group,the low-dose group and the high-dose group,and 111 differential metabolites were found,with VIP > 2.0,P<0.05,RSD<30% and in a dose-dependent manner.It was found that most of the above differential metabolites were lipid metabolites after the analysis of simple preparnation methods and database search.A total of 32 potential biomarkers were identified,including 3 phosphatidylcholine(PC),5 lysophosphatidylcholine(Lyso PC),3 ceramide(Cer),1 sphingomyelin(SM),1 phosphatidylethanolamine(PE),10 lysophosphatidylethanolamine(LysoPE),4 diacylglycerol(DG),1 Phosphatidic acid(PA),1 lysophosphatidic acid(Lyso PA),1 phosphatidyl glycerol(PG),1 fatty acid hydroxy fatty acid(FAHFA) and 1 phosphatidylserine(PS).The changes of PCs,Cers,SM,PE and DGs were closely related liver protection,DNA methylation and self-repair in hepatocytes,apoptosis,methylation and detoxification of carcinogens,as well as lipid peroxides production process.Also,they had impact on the proliferation of hepatocytes,differentiation and gene transcription disorders.Cells stimulated by NCTD-Na could promote the production of PA as well as the synthesis and catabolism of FAHFA in a variety of ways.The levels of Lyso PCs,LysoPEs and Lyso PA were correlated with PCs,PE and PA;PE and PS might have valgus during apoptosis,triggering phagocytosis.
Insights
This study identified 32 potential lipid biomarkers for in vitro hepatic injury caused by sodium norcantharidate (NCTD-Na). These biomarkers, including phosphatidylcholines and ceramides, reveal mechanisms of liver cell damage and potential pathways for protection.
Area of Science:
- Biochemistry
- Toxicology
- Metabolomics
Background:
- Sodium norcantharidate (NCTD-Na) can induce in vitro hepatic injury.
- Understanding the endogenous biomarkers and mechanisms of NCTD-Na-induced liver injury is crucial for developing protective strategies.
Purpose of the Study:
- To identify potential endogenous biomarkers of in vitro hepatic injury induced by NCTD-Na.
- To elucidate the underlying mechanisms of NCTD-Na-induced hepatic injury.
Main Methods:
- Ultra-high performance liquid chromatography coupled quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS/MS) was employed for lipidomics detection.
- Multivariate statistical analysis was used to analyze endogenous lipid metabolic changes in human normal liver cells (LO2) treated with NCTD-Na.
Main Results:
- The half maximal inhibitory concentration (IC50) of NCTD-Na was determined to be 0.034 mmol·L-1.
- Significant differences in metabolite profiles were observed between control and NCTD-Na treated groups, with 111 differential lipid metabolites identified in a dose-dependent manner.
- Thirty-two potential lipid biomarkers were identified, including phosphatidylcholines (PCs), ceramides (Cers), and lysophosphatidylcholines (Lyso PCs), among others.
Conclusions:
- The identified lipid biomarkers, such as PCs, Cers, and sphingomyelins (SMs), are closely associated with hepatocyte protection, DNA methylation, apoptosis, and detoxification processes.
- NCTD-Na treatment influences lipid metabolism, affecting hepatocyte proliferation, differentiation, and gene transcription.
- Specific lipid changes, like increased phosphatidic acid (PA) and altered lysophospholipids, provide insights into the mechanisms of NCTD-Na-induced liver injury and potential therapeutic targets.
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