MRNA expression profiles analysis of crocin mitigated triptolide-induced toxicity in mouse liver tissues
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE202175 | GEO | 2022/05/06
REPOSITORIES: GEO
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Project description:Triptolide (TP), the major active component in Tripterygium wilfordii Hook. f. (Tripterygium Glycosides), contributes to treat rheumatoid arthritis and anticancer activities. However, the organ toxicity, especially nephrotoxicity and hepatotoxicity limit its clinical application. To fully understand the mechanism underlying the triptolide induced toxicity, iTRAQ based proteomics and targeted fatty acids analysis were performed. In the present study, mouse were treated with LD50 dose of triptolide, and plasma, liver and kidney tissues were harvested before drug administration (0 h) and after drug administration (0.5 h, 1 h, 2 h, 8 h, 16 h). The blood biochemical levels (ALT, AST, BUN and CRE) were used to evaluated the toxicity of triptolide. 2D-LC-MS/MS approach was used to compare different proteins among groups 0h, 1h, 2h and 8 h. Functional annotation of different proteins in liver between different groups reveals that the top 3 pathways influenced by the TP were acute phase response signaling, antigen presentation pathway and FXR/RXR activation, the molecular and cellular functions which was mainly effected were lipid metabolism and small molecule biochemistry. In kidney, the pathway including LPS/IL-1 Mediated Inhibition of RXR Function, EIF2 Signaling, acute phase response signaling, and LXR/RXR Activation were mainly affected. The proteomics data implicated that fatty acids (FAs) may involve in the organ toxicity induced by TP. Then targeted fatty acids analysis was carried out to determinate the concentration between the different groups (0.5 h, 1 h, 2 h, 8 h, 16 h) by HPLC-MRM. We found that fatty acids in liver (C17:0, C18:0, C18:2, C18:3, C20:0, C20:3, C20:4, C22:1, C22:2, C22:3, C22:4, C22:5, C22:6, C24:0, C24:1, C24:2, C24:3, C24:4, C24:5, C24:6) show significant difference among groups, while in kidney, FAs (C12:0, C12:1, C14:0, C14:1, C16:1, C16:2) show significant difference. P450 protein family show significant change in different group, protein CYP4A14 demonstrate change in both kidney and liver tissues. By combing proteomics and targeted FAs analysis, we deeply investigated the mechanism underlying the TP induced organ toxicity, and the results may provide deeply insight into prevention or intervention in the TP clinical usage and improving its safety.
2018-07-05 | PXD005434 | Pride
Project description:Triptolide has been shown to exert various pharmacological effects on systemic autoimmune diseases and cancers. However, its severe toxicity, especially reproduction toxicity, prevents wide clinical use for those people with fertility needs. Noncoding RNAs including lncRNAs and cicrRNAs are regulatory molecules that mediate a wide variety of physiological activities, which are critical for spermatogenesis, and their dysregulation might lead to male infertility. However, whether they are involved in triptolide-induced reproduction toxicity is fully unknown. Here, after exposure of mice to triptolide for 35 day, the total RNAs were used to investigate lncRNAs/cicrRNAs/mRNAs expression profiles by strand-specific RNA sequencing at the transcriptome level to help determine any RNA-related mechanisms in triptolide-induced toxicity. The results showed that triptolide significantly decreased the testicular weight, damaged testis and sperm morphology, reduced sperm motility and density. Furthermore, there's a remarkable deformity in sperm head and tail in triptolide-exposed mice. At the transcriptome level, the triptolide-treated mice exhibited aberrant expression profiles for lncRNAs/cicrRNAs/mRNAs, many of them were dysregulated. Gene ontology and pathway analyses revealed that the functions of differentially expressed lncRNA targets, cicrRNAs cognate genes and mRNAs were closely linked with many processes involved in spermatogenesis. Additionally, many newly identified lncRNAs /cicrRNAs displayed inducible expression, suggesting that they might be good candidate markers for triptolide-induced male reproductive toxicity. This study gives us an insight into understanding the reproductive system toxicity of triptolide and reminds us to strengthen the research on increasing efficacy and decreasing toxicity of triptolide.
2020-03-23 | GSE126857 | GEO
Project description:mRNA expression profiles analysis of crocin mitigated triptolide-induced toxicity in mouse liver tissues
| PRJNA834884 | ENA
Project description:Triptolide or triptonide, major bioactive components isolated from the traditional Chinese herb Tripterygium wilfordii Hook f. (TWHF), have been shown to exert various pharmacological effects on systemic autoimmune disease. However, the severe toxicity, especially reproduction toxicity, of triptolide or triptonide prevents wide clinical use for those people with fertility needs. Long noncoding (lnc) RNAs are critical for spermatogenesis, and their dysregulation might lead to male infertility. However, whether they are involved in triptolide or triptonide -induced reproduction toxicity is unknown. Here we found that exposure of spermatocyte cell line (GC2) to triptolide or triptonide led to reduction in cell viability and induced cell apoptosis and autophagy. Then the total RNAs of triptolide or triptonide -treated GC2 cells were used to investigate lncRNA expression profiles by strand-specific RNA sequencing at the transcriptome level to help determine any RNA-related mechanisms in triptolide or triptonide-induced toxicity. Gene ontology and pathway analyses showed that the functions of differentially expressed lncRNA targets and mRNAs were closely linked with many processes involved in spermatogenesis.
2022-03-01 | GSE127662 | GEO
Project description:Expression data from treatment of actinomycin D (2.5uM) and triptolide (500 nM) on MCF7 cells for 2, 4 and 6 hours. We used microarrays to explore the mechanism of triptolide action.
2011-10-18 | GSE28662 | GEO
Project description:Pancreatic cancer is characterized by heavy desmoplasia. Triptolide and its water-soluble pro-drug Minnelide are extremely efficient against pancreatic cancer in animal models. However, the effects of triptolide on pancreatic cancer stromal cells are largely unknown. The aim of this project is to indentify potential cellular functions that are affected by triptolide in pancreatic cancer associated fibroblasts.
2016-11-01 | GSE74490 | GEO
Project description:Chronic inflammation plays important role in lung cancer development. Recently, we found that anti-inflammation drugs aspirin and triptolide when combined showed synergistic effect in suppressing lung cancer development. In this study, we aim to use gene microarray to define the genes and pathways that are affected by aspirin, triptolide individually or in combination.
2017-06-01 | GSE99514 | GEO
Project description:Significant occupational and environmental exposures to hexavalent chromium, a metal with broad toxicity potential in humans, have been reported. In order to understand the mechanisms of dermal toxicity induced by hexavalent chromium, global gene expression profiling of human dermal fibroblasts exposed to a toxic concentration of potassium dichromate was performed. Microarray analysis of the gene expression profile in the fibroblasts treated with potassium dichromate identified significant differential expression of approximately 1,200 transcripts compared with the control cells. Hierarchical cluster analysis of the gene expression profile demonstrated a clear separation of the treated cells from the control group of cells. Functional categorization of the differentially expressed genes identified the enrichment of genes involved in several cellular processes, including apoptosis and oxidative stress, in the fibroblasts exposed to hexavalent chromium. Induction of apoptosis and generation of hydroxyl radicals indicative of oxidative stress in the dermal fibroblasts in response to their exposure to hexavalent chromium were independently confirmed by TUNEL assay and electron spin resonance (ESR) analysis, respectively. The potassium dichromate-induced cytotoxicity, differential gene expression, apoptosis, and oxidative stress were significantly blocked by the addition of ferrous sulfate, an agent known for its ability to reduce hexavalent chromium to the insoluble and therefore impermeable trivalent form, to the cell culture medium. Taken together, our data provide insights into the potential mechanisms underlying the dermal toxicity of hexavalent chromium and suggest a definite role for apoptosis and oxidative stress in Cr(VI)-induced cytotoxicity in human dermal fibroblasts. 16 samples were analyzed in this experiment. Exponentially growing human dermal fibroblasts (3x105 cells) were cultured in T25 cell culture flasks. When the cells were approximately 70% confluent, hexavalent potassium dichromate (5µM) was added to the medium with or without 40µM ferrous sulfate. Following 16 hours of culturing at 37oC, total RNA was isolated for gene expression studies. Details of the samples are: Control 4 Samples: Cr(0)-1, Cr(0)-2, Cr(0)-3, Cr(0)-4 Cr 5 µM 4 Samples: Cr(5)-5, Cr(5)-6, Cr(5)-7, Cr(5)-8 FeSO4 40 µM 4 Samples: Fe(40)-9, Fe(40)-10, Fe(40)-11, Fe(40)-12 Cr 5 µM + FeSO4 40 µM 4 Samples: Cr(5)+Fe(40)-13,Cr(5)+Fe(40)-14, Cr(5)+Fe(40)-15, Cr(5)+Fe(40)-16
2011-07-30 | E-GEOD-16349 | biostudies-arrayexpress
Project description:Triptolide possesses immunosuppressive activity and its efficacy is commonly believed to be related to the suppression of T cells. However, the underlying mechanism is still not well documented and most of the previous study adopted tumor cell lines of immune system as model cells in mechanism research, these cells’ signal transduction pathway can not reflect the real situation of immune system. In this study, we investigated the immunosuppressive mechanism of triptolide on T cell activation and proliferation using mouse primary T lymphocytes. These effects were analyzed along with activation of the TCR and AP-1 pathway. We used microarrays to detail the global programme of gene expression underlying stimulation and triptolide treatment. Mouse primary T cells stimulated with anti-CD3/CD28 antibodies treated with triptolide or not treated with triptolide were selected for RNA extraction and hybridization on Affymetrix microarrays.
2012-12-29 | E-GEOD-32315 | biostudies-arrayexpress
Project description:Analyses of mirna transcript levels following exposure to the drug triptolide in vitro and prodrug minnelide in xenograft pancreatic tumor mouse models. Response of pancreatic adenocarcinoma cell lines to minelide in vitro and exposure to its prodrug triptolide in SCID mouse tumors derived from the same cell lines.
2013-11-12 | E-GEOD-46188 | biostudies-arrayexpress