Endometriosis Susceptibility to Dapsone-Hydroxylamine-Induced Alterations Can Be Prevented by Licorice Intake: In Vivo and In Vitro Study.

Chiara Sabbadin,Stefano Dall’Acqua,Anna Maria Brunati,Luciana Bordin,Decio Armanini,Guido Ambrosini,Gabriella Donà,Alessandra Andrisani,Eugenio Ragazzi,Elena Tibaldi

doi:10.3390/ijms22168476

Chiara Sabbadin, Stefano Dall’Acqua + Show 8 more

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https://doi.org/10.3390/ijms22168476

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Abstract

Endometriosis, an estrogen-dependent chronic gynecological disease, is characterized by a systemic inflammation that affects circulating red blood cells (RBC), by reducing anti-oxidant defenses. The aim of this study was to investigate the potential beneficial effects of licorice intake to protect RBCs from dapsone hydroxylamine (DDS-NHOH), a harmful metabolite of dapsone, commonly used in the treatment of many diseases. A control group (CG, n = 12) and a patient group (PG, n = 18) were treated with licorice extract (25 mg/day), for a week. Blood samples before (T0) and after (T1) treatment were analyzed for: i) band 3 tyrosine phosphorylation and high molecular weight aggregates; and ii) glutathionylation and carbonic anhydrase activity, in the presence or absence of adjunctive oxidative stress induced by DDS-NHOH. Results were correlated with plasma glycyrrhetinic acid (GA) concentrations, measured by HPLC–MS. Results showed that licorice intake decreased the level of DDS-NHOH-related oxidative alterations in RBCs, and the reduction was directly correlated with plasma GA concentration. In conclusion, in PG, the inability to counteract oxidative stress is a serious concern in the evaluation of therapeutic approaches. GA, by protecting RBC from oxidative assault, as in dapsone therapy, might be considered as a new potential tool for preventing further switching into severe endometriosis.

Highlights

One of the most common gynecological pathologies in reproductive age women is endometriosis, characterized by the presence of endometrial-like tissue in the uterine cavity [1,2].Both heme and cellular debris contribute consistently to the formation of local [3]and systemic [4] inflammation status, promoting the increased production of reactive oxygen species (ROS) and reactive nitrogen species, cytokines, growth factors, and prostaglandins [5].The presence of oxidative stress status markers in circulating red blood cells (RBCs) has been recently pointed out as a systemic feature of endometriosis [4]
Being the activity of carbonic anhydrase (CA) strictly depending on its monomerization [36], a CA activity assay was performed, with PG RBC exhibiting almost six times higher values compared to CG RBC
Sci. 2021, 22, 8476 amount of the 30 kDa band of CA increased to 24% and 49%, in CG and PG RBC, respectively, (p < 0.001), with a parallel activity increase

Summary

Introduction

One of the most common gynecological pathologies in reproductive age women is endometriosis, characterized by the presence of endometrial-like tissue in the uterine cavity [1,2] Both heme and cellular debris contribute consistently to the formation of local [3]. The presence of oxidative stress status markers in circulating red blood cells (RBCs) has been recently pointed out as a systemic feature of endometriosis [4]. Due to their fundamental role in oxygen transport, RBCs are exposed to the oxidant threat, which represents a limiting factor of the lifespan of RBCs because no new proteins can be synthesized [6]. Besides ensuring deformability, which is determined by membrane protein-protein and lipid-protein interactions, membranes provide cellular ion exchange and the expression of aging-related epitopes for RBC senescence recognition and removal

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