Abstract
A metabonomic approach based on ultra performance liquid chromatography coupled with mass spectrometry (UPLC/MS) was used to study the hepatotoxicity of ricinine in rats. Potential biomarkers of ricinine toxicity and toxicological mechanism were analyzed by serum metabonomic method. The significant differences in the metabolic profiling of the control and treated rats were clear by using the principal components analysis (PCA) of the chromatographic data. Significant changes of metabolite biomarkers like phenylalanine, tryptophan, cholic acid, LPC and PC were detected in the serum. These biochemical changes were related to the metabolic disorders in amino acids and phospholipids. This research indicates that UPLC/MS-based metabonomic analysis of serum samples can be used to predict the hepatotoxicity and further understand the toxicological mechanism induced by ricinine. This work shows that metabonomics method is a valuable tool in drug mechanism study.
Highlights
Ricinus communis, a large red and green leaved castor bean plant, can be found in tropical and subtropical climates throughout the world, which has the therapeutic effect on considered anodyne, antidote, bactericide, cathartic, expectorant, insecticide, et al The castor seed contains about 40% oil, 1–5% ricin, and 0.3–0.8% ricinine [1,2,3,4,5].Ricinine (Nr- methyl-3-cyano-4-methoxy-2-pyridone) is a toxic alkaloid that is derived from the leaves and seeds of the castor bean plant [6,7]
Analysis of ricinine by 1H-NMR The ricinine was indentified by 1H-NMR (Bruker Biospin, Germany). 1H-NMR (300 Hz, DMSO): d8.10 (1H, d, J = 7.8 Hz, 6-H), 6.43 (1H, dd, J = 7.8 Hz and J = 1.8 Hz, 5-H), 3.98 (3H, s, OCH3), 3.43 (3H, s, CH3)
The hepatocytes were in vacuolar degeneration and some nucleus were dissolved in the middle dose group
Summary
Ricinine (Nr- methyl-3-cyano-4-methoxy-2-pyridone) is a toxic alkaloid that is derived from the leaves and seeds of the castor bean plant [6,7]. Metabonomics based on the analysis of entire pattern of low molecular weight compounds rather than focusing on individual metabolites, indicates a general procedure that gives information on whole organism functional integrity over time following exposition of a perturbation. It could be defined as an attempt to measure the variation in the metabolites that are presented within cell, biofluid or tissue during the genetic modification or physiological stimulus. It has been considered to have a brighter future in the research of metabonomics
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