scholarly journals Metabolomics reveal alterations in arachidonic acid metabolism in Schistosoma mekongi after exposure to praziquantel

2021 ◽  
Vol 15 (9) ◽  
pp. e0009706
Author(s):  
Peerut Chienwichai ◽  
Phornpimon Tipthara ◽  
Joel Tarning ◽  
Yanin Limpanont ◽  
Phiraphol Chusongsang ◽  
...  
Keyword(s):  
Arachidonic Acid ◽  
Molecular Mechanisms ◽  
Acid Metabolism ◽  
Arachidonic Acid Metabolism ◽  
Drug Of Choice ◽  
Schistosoma Mekongi ◽  
Metabolomic Data ◽  
High Doses ◽  
Novel Target

Background Mekong schistosomiasis is a parasitic disease caused by the blood-dwelling fluke Schistosoma mekongi. This disease contributes to human morbidity and mortality in the Mekong region, posing a public health threat to people in the area. Currently, praziquantel (PZQ) is the drug of choice for the treatment of Mekong schistosomiasis. However, the molecular mechanisms of PZQ action remain unclear, and Schistosoma PZQ resistance has been reported occasionally. Through this research, we aimed to use a metabolomic approach to identify the potentially altered metabolic pathways in S. mekongi associated with PZQ treatment. Methodology/Principal findings Adult stage S. mekongi were treated with 0, 20, 40, or 100 μg/mL PZQ in vitro. After an hour of exposure to PZQ, schistosome metabolites were extracted and studied with mass spectrometry. The metabolomic data for the treatment groups were analyzed with the XCMS online platform and compared with data for the no treatment group. After low, medium (IC50), and high doses of PZQ, we found changes in 1,007 metabolites, of which phosphatidylserine and anandamide were the major differential metabolites by multivariate and pairwise analysis. In the pathway analysis, arachidonic acid metabolism was found to be altered following PZQ treatment, indicating that this pathway may be affected by the drug and potentially considered as a novel target for anti-schistosomiasis drug development. Conclusions/Significance Our findings suggest that arachidonic acid metabolism is a possible target in the parasiticidal effects of PZQ against S. mekongi. Identifying potential targets of the effective drug PZQ provides an interesting viewpoint for the discovery and development of new agents that could enhance the prevention and treatment of schistosomiasis.

Activity of dipyrone on intraplatelet arachidonic acid metabolism: An in vitro study

1989 ◽  
Vol 21 (1) ◽  
pp. 43-50 ◽  
Author(s):  
R ABBATE ◽  
S PINTO ◽  
A GORI ◽  
R PANICCIA ◽  
M COPPO ◽  
...  
Keyword(s):  
Arachidonic Acid ◽  
Acid Metabolism ◽  
In Vitro Study ◽  
Arachidonic Acid Metabolism ◽  
Vitro Study

scholarly journals Endogenous peroxidase in the nuclear envelope and endoplasmic reticulum of human monocytes in vitro: association with arachidonic acid metabolism

Blood ◽  
1984 ◽  
Vol 64 (2) ◽  
pp. 491-498 ◽  
Author(s):  
W Deimann ◽  
M Seitz ◽  
D Gemsa ◽  
HD Fahimi
Keyword(s):  
Endoplasmic Reticulum ◽  
Protein Synthesis ◽  
Arachidonic Acid ◽  
Nuclear Envelope ◽  
Culture Medium ◽  
Acid Metabolism ◽  
Arachidonic Acid Metabolism ◽  
Substantial Decrease ◽  
Prostaglandin E

Abstract he development of peroxidase (PO) reaction in the nuclear envelope (NE) and endoplasmic reticulum (ER) of monocytes differentiating in vitro and its relationship with arachidonic acid metabolism were studied. The PO, as visualized by the diaminobenzidine (DAB) technique, appeared in the NE and ER of the majority of monocytes within 24 hours of culture, with a substantial decrease thereafter. The influence of three major groups of agents--inhibitors of PO, of prostanoids, and of protein biosynthesis--upon the development of the PO reaction was examined. When aminotriazole, a PO inhibitor, was added to the culture medium, the appearance of PO was suppressed in the monocytes. The cyclooxygenase blocker, indomethacin, however, did not influence the development of PO. Also the blockers of protein synthesis, puromycin, cycloheximide, and actinomycin D, did not affect the appearance of PO. The prostanoids released from the monocytes, ie, prostaglandin E and thromboxane B2, were determined by radioimmunoassay and showed a time sequence of secretion that corresponded to the appearance of PO in the cells: a marked increase within the first 24 hours with a substantial decrease thereafter. The presence of the PO inhibitors aminotriazole and sodium azide in the culture medium produced a suppression of prostanoid release from the monocytes comparable with that of indomethacin. The data suggest that the PO in the NE and ER of differentiating monocytes in vitro (1) is associated with arachidonic acid metabolism, and (2) is not formed by de novo protein synthesis but rather by an activation process.

scholarly journals The influence of albumin and calcium on human platelet arachidonic acid metabolism

Blood ◽  
1980 ◽  
Vol 55 (3) ◽  
pp. 418-423 ◽  
Author(s):  
MJ Stuart ◽  
JM Gerrard ◽  
JG White
Keyword(s):  
Arachidonic Acid ◽  
Acid Metabolism ◽  
Human Platelet ◽  
Arachidonic Acid Metabolism ◽  
Albumin Concentration ◽  
Arachidonic Acid Release ◽  
Acid Release ◽  
External Calcium ◽  
Platelet Thromboxane

Abstract The effects of in vitro changes in calcium and albumin on human platelet arachidonic acid metabolism were evaluated. Hypoalbuminemia enhanced the conversion of released 14C-arachidonic acid from prelabeled platelet phospholipids to the metabolites of the platelet cyclooxygenase and lipoxygenase pathways. This effect was, however, associated with a decreased release of arachidonic acid in the presence of hypoalbuminemia, such that the overall conversion of released 14C- arachidonic acid to platelet thromboxane B2 was similar in the presence of physiologic albumin concentration (3.5 g/dl) or at decreased albumin concentrations of 0.7 and 0.0 g/dl. External calcium was shown to be important for optimal platelet arachidonic acid release, with maximal release occurring at 1 mM calcium.

scholarly journals Integrating 3-omics data analyze rat lung tissue of COPD states and medical intervention by delineation of molecular and pathway alterations

2017 ◽  
Vol 37 (3) ◽  
Author(s):  
Jiansheng Li ◽  
Peng Zhao ◽  
Liping Yang ◽  
Ya Li ◽  
Yange Tian ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Arachidonic Acid ◽  
Energy Metabolism ◽  
Molecular Mechanisms ◽  
Acid Metabolism ◽  
Inflammatory Responses ◽  
Medical Intervention ◽  
Arachidonic Acid Metabolism ◽  
Chronic Obstructive ◽  
Therapeutic Effects

Chronic obstructive pulmonary disease (COPD) is a serious health problem. However, the molecular pathogenesis of COPD remains unknown. Here, we explored the molecular effects of cigarette smoke and bacterial infection in lung tissues of COPD rats. We also investigated therapeutic effects of aminophylline (APL) on the COPD rats and integrated transcriptome, proteome, and metabolome data for a global view of molecular mechanisms of COPD progression. Using molecular function and pathway analyses, the genes and proteins regulated in COPD and APL-treated rats were mainly attributed to oxidoreductase, antioxidant activity, energy and fatty acid metabolism. Furthermore, we identified hub proteins such as Gapdh (glyceraldehyde-3-phosphate dehydrogenase), Pkm (pyruvate kinase isozymes M1/M2), and Sod1 (superoxide dismutase 1), included in energy metabolism and oxidative stress. Then, we identified the significantly regulated metabolic pathways in lung tissues of COPD- and APL-treated rats, such as arachidonic acid, linoleic acid, and α-linolenic acid metabolism, which belong to the lipid metabolism. In particular, we picked the arachidonic acid metabolism for a more detailed pathway analysis of transcripts, proteins, and metabolites. We could observe an increase in metabolites and genes involved in arachidonic acid metabolism in COPD rats and the decrease in these in APL-treated rats, suggesting that inflammatory responses were up-regulated in COPD rats and down-regulated in APL-treated rats. In conclusion, these system-wide results suggested that COPD progression and its treatment might be associated with oxidative stress, lipid and energy metabolism disturbance. Additionally, we demonstrated the power of integrated omics for the elucidation of genes, proteins, and metabolites’ changes and disorders that were associated with COPD.

The molecular biology of mammalian arachidonic acid metabolism

1991 ◽  
Vol 260 (2) ◽  
pp. L13-L28 ◽  
Author(s):  
E. Sigal
Keyword(s):  
Arachidonic Acid ◽  
Acid Metabolism ◽  
Recombinant Dna ◽  
Biological Activities ◽  
Biological Effects ◽  
Arachidonic Acid Metabolism ◽  
Bioactive Metabolites ◽  
Wide Range

The metabolism of arachidonic acid by cyclooxygenase and lipoxygenase enzymes results in a wide range of oxidized products with potent biological activities. These metabolites, which include the prostaglandins and leukotrienes, have been implicated in the pathogenesis of a variety of inflammatory diseases. Research over the last decade has focused primarily on the elucidation of the chemical structure of the metabolites and their biological effects in vitro and in vivo. Recently, research on the enzymes that produce these bioactive metabolites through oxidization of arachidonic acid has intensified. Recombinant DNA techniques have enabled investigators to determine the nucleotide sequences for several of the enzymes in the arachidonic acid cascade. The resulting cDNAs are now being used to further investigate the biochemical and biological features of arachidonic acid metabolism. The purpose of this paper is to review how the cDNAs for these enzymes were obtained, what information they convey, and how they are being applied in current research.

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