Rapid Lipidomics Analysis of Oxidised Phosphatidylcholines in Carbon Tetrachloride-Induced Acute Hepatic Injury in Mice and Their Regulation by Rhodiola crenulata Oligomeric Proanthocyanidins.

Abstract

RATIONALE: Acute hepatic injury (AHI) is a severe liver disorder that can be aggravated by oxidative stress and inflammatory responses. Oxidative stress initiates lipid peroxidation, generating a spectrum of oxidised phosphatidylcholines (oxPCs). OxPCs are commonly identified by their positional and isomeric variations. However, their structural diversity and chemical reactivity make their identification challenging. Oligomeric proanthocyanidins (OPCs) are bioactive metabolites of Rhodiola crenulata, well-known for their potential therapeutic antioxidant and anti-inflammatory effects. However, the study of alterations in oxPCs profiles associated with AHI and their regulation on Rhodiola crenulata OPC pre-treatment remains unexplored. METHODS: An induced carbon tetrachloride (CCl) AHI mouse model was constructed, and hepatic damage was assessed using biochemical and histochemical assays of the serum. An inbuilt library was developed utilising electron ionisation mass spectroscopy coupled with data-dependent scanning (ESI-DD/MS) to characterise the oxPC. Multivariate data analysis and high-resolution MS/MS fragmentation patterns enabled the identification and quantification of potential oxPC biomarkers of AHI. RESULTS: The targeted lipidomics workflow enabled the detection and quantification of 45 oxPCs, including 11 full-chain oxPCs, and 34 truncated aldehyde/carboxylate-containing oxPC subclasses. Semi-quantification of the oxPCs demonstrated an extensive accumulation of truncated oxPCs in the model, whereas OPC pre-treatment significantly suppressed the oxPC formation. The antioxidant biomarkers and hepatocellular morphology were improved, indicating the hepatoprotective effects of OPC. CONCLUSION: This study reveals that a comprehensive oxPC species profiling provides sensitive biomarkers of lipid peroxidation. By mitigating oxidative stress, restoring antioxidant enzymes and suppressing oxPCs formation, OPC demonstrates hepatoprotective effects.