Effect of Endotoxemia Induced by Intraperitoneal Injection of Lipopolysaccharide on the Mg isotopic Composition of Biofluids and Tissues in Mice.

Rosa Grigoryan,Roosmarijn E Vandenbroucke,Frank Vanhaecke,Elien Van Wonterghem,Marta Costas-Rodríguez

doi:10.3389/fmed.2021.664666

Rosa Grigoryan, Roosmarijn E Vandenbroucke + Show 3 more

Open Access

https://doi.org/10.3389/fmed.2021.664666

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Abstract

Endotoxemia induced in vivo in mice by intraperitoneal injection of lipopolysaccharide (LPS) leads to (neuro)inflammation and sepsis. Also the homeostasis of mineral elements can be altered through mechanisms that still are poorly understood. The isotopic composition of Mg and the concentrations of the minor elements Ca, K, Mg, Na, P, and S were determined in biological fluids and tissues of young (14–28 weeks) and aged (40–65 weeks) LPS-injected mice and age-matched controls to reveal potential effects of the LPS-induced infection. Blood plasma of young and aged LPS-injected mice showed a heavy Mg isotopic composition, as well as elevated Mg and P concentrations, compared to matched controls. The plasma Mg isotopic composition was correlated with the P concentration in aged mice. Also the liver Mg isotopic composition was strongly affected in the young and aged LPS-injected mice, while for aged mice, an additional effect on the urine Mg isotopic composition was established. These observations were hypothetically associated with liver inflammation and/or hepatotoxicity, and reduced urinary Mg excretion, respectively. Also a regional endotoxin-induced difference was observed in the brain Mg isotopic composition for the aged mice only, and was attributed to potential disruption of the blood-brain barrier.

Highlights

Lipopolysaccharide (LPS) is a structural component of the outer membrane (OM) of Gramnegative bacteria (GNB), which consists of three main components—lipid A, the core oligosaccharide, and the O-polysaccharide or O-antigen [1]
The Mg isotopic composition was not correlated with the Mg mass fraction, but showed correlation with the P concentration
adenosine triphosphate (ATP) depletion induced by the LPS may contribute to an enrichment in the heavier Mg isotopes in the blood plasma

Summary

Introduction

Lipopolysaccharide (LPS) is a structural component of the outer membrane (OM) of Gramnegative bacteria (GNB), which consists of three main components—lipid A (which is held responsible for the toxicity of the endotoxin), the core oligosaccharide, and the O-polysaccharide or O-antigen [1]. The administration of LPS in vivo is a well-established experimental model of endotoxemia, inducing (neuro)inflammation and sepsis in mice [3]. Various molecular changes have been found to occur under such circumstances, depending on the animal model, age and/or LPS treatment applied, i.e., a single vs systemic dose, type of injection (subcutaneous, intraperitoneal, or intracerebroventricular), the LPS concentration administered and the duration of the treatment [6,7,8]. The endotoxemia-induced toxicity leads to injuries in several organs, liver, kidneys, lungs, and brain [11]. The liver plays a major role in the infection, as it takes up the infused LPS after the injection, rendering it the major localization of the LPS [12], and has the ability to clear the LPS to prevent it from entering into the systemic blood stream [13]. Detection and monitoring of endotoxemia can play an important role in evaluating the progression of such disease [14]

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