**5. Conclusions**

Endometriosis RBC membranes are characterized by high oxidative levels, which impairs the RBC response to a potential high oxidant therapy, such as in the case of DDS, commonly used for the treatments of leprosy, malaria, and autoimmune diseases. DDS-NHOH, a DDS metabolite, exasperates the oxidative status of the patients' RBCs. The resulting condition leads to a premature RBC removal from circulation as an index of reduced RBC life-span due to the overwhelming oxidative assault [24]. It is also involved in a potential further worsening of patients' conditions by increasing the oxidative stress

which, in turn, may also trigger genetic/epigenetic cell transformation [38,39]. The DDS-NHOH-related further drop in the total glutathione content was also responsible for the serious increase of CA activity, thus bringing new concerns for the development of further complications, such as glaucoma [45].

After licorice intake, the GSH loss was clearly reduced, showing a net improvement of the cell anti-oxidant defenses, as confirmed by the related reduction of CA monomerization and activation. A similar protective effect of GA also mitigated DDS-NHOH induced side effects by lowering membrane sensitivity to oxidative stress and preserving the cell GSH content.

In conclusion, the results demonstrate that licorice intake prevented/ameliorated the oxidative stress generated by a strong oxidizing agent, a byproduct of a commonly used therapy, in RBCs already seriously struggling with an endometriosis-related inflammatory status—but it is far from being an endometriosis therapy. Our study represents a promising pilot study that would request further investigations to better evaluate licorice potential in inflammatory diseases.

**Supplementary Materials:** The following are available online at https://www.mdpi.com/article/10 .3390/ijms22168476/s1.

**Author Contributions:** Conceptualization D.A. and L.B.; data curation, C.S., A.A., G.D., E.T., A.M.B., S.D., E.R. and L.B.; formal analysis, C.S., A.A., G.D., E.T., A.M.B., E.R., D.A. and L.B.; funding acquisition, D.A.; investigation, C.S., A.A.,G.D., S.D. and L.B.; methodology, C.S., A.A., G.D., E.T., A.M.B., S.D., E.R., D.A. and L.B.; project administration, D.A. and L.B.; supervision, G.A. and D.A.; validation, E.R.; writing—original draft, C.S., A.A., G.D., E.T., A.M.B., S.D., E.R., G.A., D.A. and L.B.; writing—review and editing, C.S., A.A., G.D., E.R., G.A., D.A. and L.B. All authors have read and agreed to the published version of the manuscript.

**Funding:** This work was supported by the Italian Ministero dell'Università e della Ricerca Scientifica e Tecnologica (MURST, grant N. 60A06-0558/12). Doctors C. Sabbadin and G. Donà were partially supported by grants from Katjes Fassin GmbH + Co. KG, Emmerich (Germany).

**Institutional Review Board Statement:** This study was conducted in accordance with the ethical standards of the Ethics Committee for Research and Clinical Trials of our University (Em. n. 7, 13 February 2012) and with the Helsinki Declaration.

**Informed Consent Statement:** Informed consent was obtained from all subjects involved in the study.

**Data Availability Statement:** The data presented in this study are available in the article.

**Conflicts of Interest:** The authors declare no conflict of interest.
