Integrative analysis of proteomic and metabonomics data for identification of pathways related to Rhizoma Paridis-induced hepatotoxicity

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.Rhizoma Paridis, the roots of the Paris polyphylla Smith var. (Franch.), was first recorded in 'Shennong Herb' and Li Shizhen's 'Compendium of Materia' . The prepared Rhizoma Paridis has remarkable therapeutic effects on fractures, parotitis, hemostasis, snake bite, and abscess in the clinic for thousands of years. In addition, modern pharmacology indicated that Raw Rhizoma Paridis has beneficial impact on anti-tumor, immunity adjustment, analgesia, and anti-inflammation 1-3 . However, clinical researches regarding adverse reactions caused by Rhizoma Paridis and its preparations 4 , especially hepatotoxicity, have attracted significant attention in recent years 5 . 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 .Recently, omic technologies are becoming important in vitro and in vivo tools for identifying potential hepatotoxicity mechanisms. 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 1

A discovery-based proteomics approach identifies protein disulphide isomerase (PDIA1) as a biomarker of β cell stress in type 1 diabetes

“…Among the top proteins upregulated in diabetes resistant mice and down-regulated in diabetic mice were IAPP and antioxidant-1 (ATOX1), a copper chaperone shown to be protective against hydrogen peroxide and superoxide mediated-oxidative stress. 46 Other key proteins showing this pattern of expression were proteasome subunit beta 10 (PSB10), which is involved in the maintenance of protein homeostasis, 47 coactosin like protein (COTL1), an F-actin-binding protein that plays a role in cellular growth, 48 and S100A4, which functions as an intracellular cytosolic calcium sensor. 49 , 50

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A discovery-based proteomics approach identifies protein disulfide isomerase (PDIA1) as a biomarker of β cell stress in type 1 diabetes

“…Among the top proteins upregulated in diabetes resistant mice and down-regulated in diabetic mice were IAPP and antioxidant-1 (ATOX1), a copper chaperone shown to be protective against hydrogen peroxide and superoxide mediated-oxidative stress (34). Other key proteins showing this pattern of expression were proteasome subunit beta 10 (PSB10), which is involved in the maintenance of protein homeostasis (35), coactosin like protein (COTL1), an F-actin-binding protein that plays a role in cellular growth (36); and S100A4, which functions as an intracellular cytosolic calcium sensor (37, 38).…”

Safety of high‐dose Puerariae Lobatae Radix in adolescent rats based on metabolomics

“…The liver, kidney, breast, testis, epididymis, ovary, and uterus tissues of the high‐dose group were fixed, dehydrated, embedded, sectioned, and hematoxylin and eosin (HE)‐stained. Sections were examined under a microscope at 40× and 100× (Liu et al., 2014; Zhao et al., 2020).…”