Abstract
Clinical reports on hepatotoxicity that arise from Rhizoma Paridis have recently received widespread attention. Because the hepatotoxicity mechanism is little understood, this research strived to investigate the hepatotoxicity mechanism of Rhizoma Paridis extracts based on iTRAQ quantitative proteomics and metabonomics. The extraction solutions were administrated to rats for 7 days by gavage, and the hepatotoxicity was assessed through quantification of biochemical indexes and Oil red O staining. Additionally, the mechanism of hepatotoxicity was investigated by metabonomics based upon GC-MS and iTRAQ quantitative proteomics. The biochemical and histopathological analysis stood out that Rhizoma Paridis extract could induce liver injury, which was proved by the formation of fat droplets, the changes of mitochondrial structure, and biochemical parameters. The iTRAQ proteomics and metabonomics revealed that Rhizoma Paridis-induced hepatotoxicity was chiefly connected with the abnormal activity of mitochondrion function, which brought about oxidative stress injuries and inflammation, finally causing cell apoptosis. Collectively, we have provided previously uncharacterized hepatotoxic mechanism induced by Rhizoma Paridis and a reference to ensure its safe use in the future.
Highlights
Clinical reports on hepatotoxicity that arise from Rhizoma Paridis have recently received widespread attention
In accordance with the result of metabolomics, iTRAQ quantitative proteomics, the liver histopathology, the biochemical index, we found that Rhizoma Paridis-induced hepatotoxicity can be attributed to the imbalance of energy and lipid metabolism, so that mediated a procession of pathological responses including inflammation, oxidative stress injury, and apoptosis, engendering liver injury
Previous evidence indicates that fat accumulation mediated the oxidative stress injury, inflammation, www.nature.com/scientificreports and apoptosis that are involved in Rhizoma Paridis-induced hepatotoxicity
Summary
Clinical reports on hepatotoxicity that arise from Rhizoma Paridis have recently received widespread attention. The Chinese Pharmacopoeia clearly describes its hypotoxicity and reminds the patient and doctor to note the possible problems of orally ingesting Rhizoma Paridis and its drug preparations in high doses or over prolonged periods and when taken with other liver-damaging drugs Despite these warnings, the mechanisms remained little known[6]. The proteomics can identify the differentially expressed proteins that occur in a specific function, which may involve disease- or disorder-related changes in transcription, translation, transport, degradation, and covalent modification[7,8] Metabolomics is another powerful technology for identifying a number of low-molecular-weight endogenous metabolites and assessing the dynamic variations in the biological samples www.nature.com/scientificreports in response to different stimuli[9,10]. Our data provided cognizance of the rational clinical application of Rhizoma Paridis and supported a promising strategy for detoxifying
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