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

**Chiara Sabbadin <sup>1</sup> , Alessandra Andrisani <sup>2</sup> , Gabriella Donà 3 , Elena Tibaldi <sup>3</sup> , Anna Maria Brunati <sup>3</sup> , Stefano Dall'Acqua <sup>4</sup> , Eugenio Ragazzi <sup>4</sup> , Guido Ambrosini <sup>2</sup> , Decio Armanini 1,\* and Luciana Bordin 3,\***


**Citation:** Sabbadin, C.; Andrisani, A.; Donà, G.; Tibaldi, E.; Brunati, A.M.; Dall'Acqua, S.; Ragazzi, E.; Ambrosini, G.; Armanini, D.; Bordin, L. Endometriosis Susceptibility to Dapsone-Hydroxylamine-Induced Alterations Can Be Prevented by Licorice Intake: In Vivo and In Vitro Study. *Int. J. Mol. Sci.* **2021**, *22*, 8476. https://doi.org/10.3390/ijms22168476


Academic Editor: Christopher L. Gentile

Received: 30 June 2021 Accepted: 3 August 2021 Published: 6 August 2021

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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 (T<sup>0</sup> ) and after (T<sup>1</sup> ) 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.

**Keywords:** endometriosis; dapsone; DDS-NHOH; red blood cell; glycyrrhetinic acid
