Comparative Study of Lipid Profile for Mice Treated with Cyclophosphamide by HPLC-HRMS and Bioinformatics

Overview

Journal Metabolites

Publisher MDPI

Date 2025 Jan 24

PMID 39852402

Authors

Ekaterina Demicheva

Fernando Jonathan Polanco Espino

Pavel Vedeneev

Vadim Shevyrin

Aleksey Buhler

Elena Mukhlynina

Olga Berdiugina

Alicia Del Carmen Mondragon

Alberto Cepeda Saez

Aroa Lopez-Santamarina

Alejandra Cardelle-Cobas

Olga Solovyova

Irina Danilova

Jose Manuel Miranda

Elena Kovaleva

Affiliations

Soon will be listed here.

Abstract

Immunodeficiency conditions, which are characterized by reduced immune activity that promotes the development of chronic diseases, are needed for efficient monitoring. A promising area of monitoring and early diagnosis of immunodeficiency diseases is the determination of metabolic biomarkers in the blood. In this work, we identified a set of lipid biomarkers of immunodeficiency states by performing high-performance liquid chromatography-high-resolution mass spectrometry (HPLC-HRMS) analysis of blood plasma samples from mice and processing them with bioinformatics approaches. Potential biomarkers were selected through statistical analysis and further validated by MS/MS. As a result, 15 lipids were confirmed and selected as potential biomarkers of immunodeficiency states. The selected biomarkers can be further studied and serve as promising targets for the early diagnosis of immunodeficiency diseases.

References

Zhou Q, Gao J, Sun X, Du J, Wu Z, Liang D . Immunomodulatory Mechanisms of Tea Leaf Polysaccharide in Mice with Cyclophosphamide-Induced Immunosuppression Based on Gut Flora and Metabolomics. Foods. 2024; 13(18). PMC: 11431025. DOI: 10.3390/foods13182994. View

Matyash V, Liebisch G, Kurzchalia T, Shevchenko A, Schwudke D . Lipid extraction by methyl-tert-butyl ether for high-throughput lipidomics. J Lipid Res. 2008; 49(5):1137-46. PMC: 2311442. DOI: 10.1194/jlr.D700041-JLR200. View

de Jonge M, Huitema A, Rodenhuis S, Beijnen J . Clinical pharmacokinetics of cyclophosphamide. Clin Pharmacokinet. 2005; 44(11):1135-64. DOI: 10.2165/00003088-200544110-00003. View

Ibrahim K, Darwish S, Mantawy E, El-Demerdash E . Molecular mechanisms underlying cyclophosphamide-induced cognitive impairment and strategies for neuroprotection in preclinical models. Mol Cell Biochem. 2023; 479(8):1873-1893. PMC: 11339103. DOI: 10.1007/s11010-023-04805-0. View

Wegner M, Schiffmann S, Parnham M, Geisslinger G, Grosch S . The enigma of ceramide synthase regulation in mammalian cells. Prog Lipid Res. 2016; 63:93-119. DOI: 10.1016/j.plipres.2016.03.006. View

OConnor A, Brasher C, Slatter D, Meckelmann S, Hawksworth J, Allen S . LipidFinder: A computational workflow for discovery of lipids identifies eicosanoid-phosphoinositides in platelets. JCI Insight. 2017; 2(7):e91634. PMC: 5374061. DOI: 10.1172/jci.insight.91634. View

Conroy M, Andrews R, Andrews S, Cockayne L, Dennis E, Fahy E . LIPID MAPS: update to databases and tools for the lipidomics community. Nucleic Acids Res. 2023; 52(D1):D1677-D1682. PMC: 10767878. DOI: 10.1093/nar/gkad896. View

Libiseller G, Dvorzak M, Kleb U, Gander E, Eisenberg T, Madeo F . IPO: a tool for automated optimization of XCMS parameters. BMC Bioinformatics. 2015; 16:118. PMC: 4404568. DOI: 10.1186/s12859-015-0562-8. View

Fobofou S, Savidge T . Microbial metabolites: cause or consequence in gastrointestinal disease?. Am J Physiol Gastrointest Liver Physiol. 2022; 322(6):G535-G552. PMC: 9054261. DOI: 10.1152/ajpgi.00008.2022. View

10.

Prince J, Marcotte E . Chromatographic alignment of ESI-LC-MS proteomics data sets by ordered bijective interpolated warping. Anal Chem. 2006; 78(17):6140-52. DOI: 10.1021/ac0605344. View

11.

Trifonova O, Maslov D, Balashova E, Lokhov P . Current State and Future Perspectives on Personalized Metabolomics. Metabolites. 2023; 13(1). PMC: 9863827. DOI: 10.3390/metabo13010067. View

12.

Shirani K, Hassani F, Razavi-Azarkhiavi K, Heidari S, Riahi Zanjani B, Karimi G . Phytotrapy of cyclophosphamide-induced immunosuppression. Environ Toxicol Pharmacol. 2015; 39(3):1262-75. DOI: 10.1016/j.etap.2015.04.012. View

13.

Tsugawa H, cajka T, Kind T, Ma Y, Higgins B, Ikeda K . MS-DIAL: data-independent MS/MS deconvolution for comprehensive metabolome analysis. Nat Methods. 2015; 12(6):523-6. PMC: 4449330. DOI: 10.1038/nmeth.3393. View

14.

Smith C, Want E, OMaille G, Abagyan R, Siuzdak G . XCMS: processing mass spectrometry data for metabolite profiling using nonlinear peak alignment, matching, and identification. Anal Chem. 2006; 78(3):779-87. DOI: 10.1021/ac051437y. View

15.

Cengiz M . Hematoprotective effect of boron on cyclophosphamide toxicity in rats. Cell Mol Biol (Noisy-le-grand). 2018; 64(5):62-65. View

16.

Xu J, Fang H, Chong Y, Lin L, Xie T, Ji J . Cyclophosphamide Induces Lipid and Metabolite Perturbation in Amniotic Fluid during Rat Embryonic Development. Metabolites. 2022; 12(11). PMC: 9693482. DOI: 10.3390/metabo12111105. View

17.

Zhu R, Wang Y, Zhang L, Guo Q . Oxidative stress and liver disease. Hepatol Res. 2012; 42(8):741-9. DOI: 10.1111/j.1872-034X.2012.00996.x. View

18.

Levesque J, Hendy J, Takamatsu Y, Simmons P, Bendall L . Disruption of the CXCR4/CXCL12 chemotactic interaction during hematopoietic stem cell mobilization induced by GCSF or cyclophosphamide. J Clin Invest. 2003; 111(2):187-96. PMC: 151860. DOI: 10.1172/JCI15994. View

19.

Chen S, Inui S, Aisyah R, Nakashima R, Kawaguchi T, Hinomoto M . Role of Gpcpd1 in intestinal alpha-glycerophosphocholine metabolism and trimethylamine N-oxide production. J Biol Chem. 2024; 300(12):107965. PMC: 11652876. DOI: 10.1016/j.jbc.2024.107965. View

20.

Jeelani R, Khan S, Shaeib F, Kohan-Ghadr H, Aldhaheri S, Najafi T . Cyclophosphamide and acrolein induced oxidative stress leading to deterioration of metaphase II mouse oocyte quality. Free Radic Biol Med. 2017; 110:11-18. PMC: 6854673. DOI: 10.1016/j.freeradbiomed.2017.05.006. View