title: The combination of N-acetyl cysteine, alpha-lipoic acid, and bromelain shows high anti-inflammatory properties in novel in vivo and in vitro models of endometriosis.
abstract: To evaluate the efficacy of an association of N-acetyl cystein, alpha-lipoic acid, and bromelain (NAC/LA/Br) in the treatment of endometriosis we set up a new in vivo murine model. We explored the anti-inflammatory and proapoptotic effect of this combination on human endometriotic endothelial cells (EECs) and on endothelial cells isolated from normal uterus (UtMECs). We implanted fragments of human endometriotic cysts intraperitoneally into SCID mice to evaluate the efficacy of NAC/LA/Br treatment. UtMECs and EECs, untreated or treated with NAC/LA/Br, were activated with the proinflammatory stimulus TNF-α and their response in terms of VCAM1 expression was evaluated. The proapoptotic effect of higher doses of NAC/LA/Br on UtMECs and EECs was measured with a fluorogenic substrate for activated caspases 3 and 7. The preincubation of EECs with NAC/LA/Br prior to cell stimulation with TNF-α prevents the upregulation of the expression of the inflammatory "marker" VCAM1. Furthermore NAC/LA/Br were able to induce EEC, but not UtMEC, apoptosis. Finally, the novel mouse model allowed us to demonstrate that mice treated with NAC/LA/Br presented a lower number of cysts, smaller in size, compared to untreated mice. Our findings suggest that these dietary supplements may have potential therapeutic uses in the treatment of chronic inflammatory diseases like endometriosis.
authors.affiliation: Institute for Maternal and Child Health, IRCCS Burlo Garofolo, 34137 Trieste, Italy.
authors.forename: C
authors.initials: C
authors.lastname: Agostinis
authors.affiliation: Department of Life Sciences, University of Trieste, Via Valerio 28, 34127 Trieste, Italy.
authors.forename: S
authors.initials: S
authors.lastname: Zorzet
authors.affiliation: Institute for Maternal and Child Health, IRCCS Burlo Garofolo, 34137 Trieste, Italy.
authors.forename: R
authors.initials: R
authors.lastname: De Leo
authors.affiliation: Institute for Maternal and Child Health, IRCCS Burlo Garofolo, 34137 Trieste, Italy.
authors.forename: G
authors.initials: G
authors.lastname: Zauli
authors.affiliation: Institute for Maternal and Child Health, IRCCS Burlo Garofolo, 34137 Trieste, Italy ; Department of Medical, Surgical and Health Sciences, University of Trieste, Ospedale di Cattinara, Strada di Fiume 447, 34149 Trieste, Italy.
authors.forename: F
authors.initials: F
authors.lastname: De Seta
authors.affiliation: Department of Life Sciences, University of Trieste, Via Valerio 28, 34127 Trieste, Italy.
authors.forename: R
authors.initials: R
authors.lastname: Bulla
mesh_terms: D000111:Acetylcysteine / Q000008:administration & dosage*; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage*; D017209:Apoptosis; D001963:Bromelains / Q000008:administration & dosage*; D002478:Cells, Cultured; D004195:Disease Models, Animal; D004715:Endometriosis / Q000188:drug therapy*; D042783:Endothelial Cells / Q000187:drug effects; D005260:Female; D006801:Humans; D007249:Inflammation / Q000378:metabolism; D051379:Mice; D016513:Mice, SCID; D008856:Microscopy, Fluorescence; D008063:Thioctic Acid / Q000008:administration & dosage*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D014599:Uterus / Q000166:cytology; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism
chemical_list: D000893:Anti-Inflammatory Agents; D014409:Tumor Necrosis Factor-alpha; D019010:Vascular Cell Adhesion Molecule-1; D008063:Thioctic Acid; D001963:Bromelains; D000111:Acetylcysteine