IMR Press / FBL / Volume 27 / Issue 8 / DOI: 10.31083/j.fbl2708230
Open Access Original Research
Cellular Respiration in Thymic Fragments from Mice
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1 Department of Microbiology and Immunology, College of Medicine and Health Sciences, UAE University, 15551 Al Ain, Abu Dhabi, United Arab Emirates
2 Department of Pediatrics, College of Medicine and Health Sciences, UAE University, 15551 Al Ain, Abu Dhabi, United Arab Emirates
*Correspondence: asouid@uaeu.ac.ae (Abdul-Kader Souid)
Academic Editor: Mateusz Maciejczyk
Front. Biosci. (Landmark Ed) 2022, 27(8), 230; https://doi.org/10.31083/j.fbl2708230
Submitted: 18 May 2022 | Revised: 8 July 2022 | Accepted: 18 July 2022 | Published: 29 July 2022
(This article belongs to the Special Issue Mitochondrial Dysfunction in Acute and Chronic Neurodegeneration)
Copyright: © 2022 The Author(s). Published by IMR Press.
This is an open access article under the CC BY 4.0 license.
Abstract

Background: This report aims to detail the use of the phosphorescence oxygen analyzer for in vitro investigation of thymic responses to pharmaceutical agents, in particular immunosuppressants and immunomodulators. Sirolimus (a highly specific inhibitor of the ‘molecular target of rapamycin’, mTOR) and ozanimod (an agonist of the sphingosine 1-phosphate receptor, recently approved for treatment of multiple sclerosis and ulcerative colitis) are used for this purpose. Methods: Thymic fragments from mice were placed in glass vials containing phosphate-buffered saline, bovine albumin, and Pd(II) meso-tetra (sulfophenyl) tetrabenzoporphyrin. The vials were sealed from air, and the cellular oxygen consumption was monitored as function of time. Results: The decline of dissolved oxygen concentration with time (d[O2]/dt) was linear; thus, its rate (thymocyte respiration) was expressed as μM O2 min-1. Cyanide inhibited respiration, confirming the oxygen consumption was in cytochrome oxidase. In age-matched mice, the rate of thymocyte respiration (mean ± SD, in μM O2 min-1 mg-1) was 0.046 ± 0.011 (median = 0.043, range = 0.028 to 0.062, n = 10). In thymic fragments from littermates, this rate was inhibited in the presence of sirolimus (16% lower) or ozanimod (29% lower). Conclusions: Thymocyte respiration can serve as a surrogate biomarker for studying the mode-of-action and the cytotoxicity of immunotoxins and immunosuppressants.

Keywords
thymus
mTOR
sirolimus
ozanimod
cellular respiration
cellular bioenergetics
immunosuppressants
immunotoxins
Figures
Fig. 1.
Funding
31M470/College of Medicine & Health Sciences UAE University
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