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Chemical carcinogenicity of neodymium nitrate in AML12 hepatocytes: Dose-response metabolomics and sensitive
Ning Wang1, Da-Sheng Lu1, Jing Leng1
1Shanghai Municipal Center for Disease Control and Prevention, Institute of Chemical Toxicity Identification / National Health Commission Food Safety Risk Assessment and Standard Development Key Laboratory / National Environmental Protection Key Laboratory of Environmental Health Impact Assessment for Emerging Pollutants, Shanghai, China.
Abstract:
This study aims to investigate the chemical carcinogenic toxicity of neodymium nitrate (Nd(NO3)3) in mouse hepatocytes AML12 using dose-response metabolomics. Specifically, our objectives are to: Identify key metabolites that respond to Nd(NO3)3 exposure. Elucidate the mechanisms underlying Nd(NO3)3-induced liver toxicity. Provide a scientific basis for risk assessment of Nd(NO3)3 exposure. AML12 cells were exposed to different concentrations of Nd(NO3)3 (0, 0.2, 0.4, and 0.8 µM) for 24 h. Metabolite changes were analyzed using UPLC-MS, and differential metabolites (DMs) were identified. Key metabolic pathways affected by Nd(NO3)3 include amino acid metabolism, nucleotide metabolism, and energy metabolism. Significant changes in these pathways suggest that Nd(NO3)3 induces metabolic disturbances that may lead to cytotoxicity. We identified potential biomarkers, such as UDP-N-acetylglucosamine, L-glutathione, and glycine, which exhibit dose-dependent responses. These findings provide insights into the mechanisms of Nd(NO3)3-induced chemical carcinogenicity and offer a scientific basis for risk assessment. Future research should further explore the toxicity and mechanisms in in vivo settings. CONCLUSION: Our study reveals that Nd(NO3)3 induces metabolic disturbances in AML12 hepatocytes, leading to potential cytotoxicity. The identified potential biomarkers, such as UDP-N-acetylglucosamine, L-glutathione, and glycine, provide a basis for early detection and risk assessment of Nd(NO3)3 exposure. Further in vivo studies are needed to explore the long-term effects and mechanisms of Nd(NO3)3 toxicity.
Insights
Neodymium nitrate (Nd(NO₃)₃) exposure causes metabolic disturbances in mouse liver cells, potentially leading to toxicity. Identified biomarkers like UDP-N-acetylglucosamine aid in risk assessment for Nd(NO₃)₃.
Area of Science:
- Hepatotoxicity
- Metabolomics
- Chemical Carcinogenicity
Background:
- Neodymium nitrate (Nd(NO₃)₃) is a chemical compound with potential toxicological implications.
- Understanding its effects on liver cells is crucial for risk assessment.
Purpose of the Study:
- Investigate the chemical carcinogenic toxicity of Nd(NO₃)₃ in mouse hepatocytes (AML12 cells).
- Identify key metabolites and elucidate mechanisms of Nd(NO₃)₃-induced liver toxicity.
- Provide a scientific basis for risk assessment of Nd(NO₃)₃ exposure.
Main Methods:
- Dose-response metabolomics analysis of AML12 cells exposed to varying Nd(NO₃)₃ concentrations (0-0.8 µM).
- Ultra-Performance Liquid Chromatography-Mass Spectrometry (UPLC-MS) for metabolite profiling.
- Identification of differential metabolites (DMs) and affected metabolic pathways.
Main Results:
- Nd(NO₃)₃ exposure significantly altered amino acid, nucleotide, and energy metabolism in AML12 cells.
- Potential biomarkers, including UDP-N-acetylglucosamine, L-glutathione, and glycine, showed dose-dependent responses.
- Metabolic disturbances suggest potential Nd(NO₃)₃-induced cytotoxicity.
Conclusions:
- Nd(NO₃)₃ induces metabolic disturbances and potential cytotoxicity in hepatocytes.
- Identified biomarkers (UDP-N-acetylglucosamine, L-glutathione, glycine) can aid in early detection and risk assessment.
- Further in vivo studies are warranted to investigate long-term effects and mechanisms.
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