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
Agostinis C,Zorzet S,De Leo R,Zauli G,De Seta F,Bulla R
Published May 12, 2015Mediators of Inflammation, 2015(1), 918089
Agostinis, C., Zorzet, S., De Leo, R., Zauli, G., De Seta, F., & Bulla, R. (2015). 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. Mediators of inflammation, 2015(1), 918089. https://doi.org/10.1155/2015/918089
Agostinis C, Zorzet S, De Leo R, Zauli G, De Seta F, Bulla R. 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. Mediators Inflamm. 2015;2015(1):918089. doi:10.1155/2015/918089
Agostinis, Chiara, et al. "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." Mediators of inflammation, vol. 2015, no. 1, 2015, pp. 918089.
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Mice given NAC, lipoic acid, bromelain had fewer endometriosis cysts
A 2015 study found that mice given a mix of three supplements grew fewer endometriosis cysts. The mix was N-acetyl cysteine, alpha-lipoic acid and bromelain. Human endometriosis tissue was injected into the abdomen of mice. Seven got the mix and 9 did not. Human cell tests came next.
Key Findings
All 9 untreated mice grew at least 1 cyst, and some grew up to 4.
Among the 7 treated mice, 4 had no visible cyst and 3 had 1 cyst. The authors report a statistically significant difference in cyst number.
Cysts in untreated mice were larger than cysts in treated mice.
In cells from 5 patients, the combination gave a statistically significant but incomplete drop in the inflammation marker VCAM1. In the same cell tests, each ingredient alone gave little or no drop.
In cell tests at higher amounts, the combination triggered cell death in endometriosis endothelial cells and had no effect on endothelial cells from normal uterus.
Interpretation
The study is preclinical: dish experiments plus a small mouse experiment lasting 21 days. The mice received added estrogen and implanted human tissue. The results describe these models. The experiments used mice and cells, and no women took the supplements. The authors call for a further study comparing the combination with standard therapies. PiZeta Pharma, whose product the mixture was modeled on, donated funds for the work.
RRM Context
The paper's introduction names surgical removal of lesions as the first-line step. Restorative reproductive medicine endorses excision as the surgical standard. Counting cysts in mice tells us about lesion growth in animals. Evidence on disease progression in women comes from human studies.
Our editorial summary of this paper, not the article's abstract.
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.
The sector of the market that deals with contraception offers a long list of different contraceptive methods. Within the estroprogestinic choice, the routes of administration are oral, transdermic and vaginal one. Even though efficacy is comparable with these methods, secondary and adverse effects are directly involved in the acceptability of the method. This was a prospective comparative study. During 1 year, we enrolled 60 asymptomatic women who voluntarily requested combined oral contraception (COC) or combined contraceptive vaginal ring (CCVR group). After a baseline study of vaginal milieu prior to starting hormonal contraception, we performed a follow-up. For each woman, we examined vaginal pH; quantification of leukocytes, lactobacilli, Candida and cocci on saline microscopy fluid; Gram stain with Nugent score and the presence of vaginal infection [culture for Trichomonas vaginalis, albicans and nonalbicans Candida, Group B Streptococcus (GBS)]. At the end of follow-up, there was a little change of vaginal milieu in both groups. We noted an increase of lactobacilli in the CCVR users and an increase of GBS in COC users. CCVR compared to COC users showed an increase of the number of lactobacilli in vaginal flora. It means that an increase of leukorrhea in that group could be protective in terms of prevention of vaginal imbalance/infection.
Anastasi E et al., 2023·International journal of environmental research and public health·Free full text on PubMed Central
Endometriosis is a chronic, estrogen-dependent, inflammatory disease, whose pivotal symptoms are dysmenorrhea, dyspareunia, and chronic pelvic pain (CPP). Besides the usual medical treatments, recent evidence suggests there are potential benefits of oral N-acetylcysteine (NAC) on endometriotic lesions and pain. The primary objective of this prospective single-cohort study was to confirm the effectiveness of NAC in reducing endometriosis-related pain and the size of ovarian endometriomas. The secondary objective was to assess if NAC may play a role in improving fertility and reducing the Ca125 serum levels. Patients aged between 18-45 years old with a clinical/histological diagnosis of endometriosis and no current hormonal treatment or pregnancy were included in the study. All patients received quarterly oral NAC 600 mg, 3 tablets/day for 3 consecutive days of the week for 3 months. At baseline and after 3 months, dysmenorrhea, dyspareunia and CPP were assessed using the Visual Analog Scale score (VAS), while the size of the endometriomas was estimated through a transvaginal ultrasound. Analgesics (NSAIDs) intake, the serum levels of Ca125 and the desire for pregnancy were also investigated. Finally, the pregnancy rate of patients with reproductive desire was evaluated. One hundred and twenty patients were recruited. The intensity of dysmenorrhea, dyspareunia and CPP significantly improved (p < 0.0001). The use of NSAIDs (p = 0.001), the size of the endometriomas (p < 0.0001) and the serum levels of Ca125 (p < 0.0001) significantly decreased. Among the 52 patients with reproductive desire, 39 successfully achieved pregnancy within 6 months of starting therapy (p = 0.001). Oral NAC improves endometriosis-related pain and the size of endometriomas. Furthermore, it decreases Ca125 serum levels and may improve fertility in patients with endometriosis.
The role of natural killer (NK) cells in the decreased cellular immunity of women with endometriosis was investigated. DESIGN, SETTING, Thirty-four women were investigated prospectively before a CO2-laser laparoscopy for infertility and/or pain at the University Hospital Gasthuisberg. Endometriosis was scored blindly. The cytotoxicity, directed against the endometrium, was mediated by NK cells because this cytotoxicity could be removed by treating the effector cells with the NK-specific anti-Leu-11b monoclonal antibody. Consequently, we evaluated prospectively in those women the lymphocyte-mediated cytotoxicity toward NK sensitive (K562-assay) and autologous endometrial target cells. The NK activity (K562-assay) and the cytotoxicity against autologous endometrial cells were similarly decreased in women with endometriosis and correlated with the severity of the disease. Using heterologous effector cells, the decreased chromium release in women with endometriosis was less pronounced but still present. The decreased cytotoxicity to endometrial cells in women with endometriosis is mainly because of a defect in NK activity but is also partially because of a resistance of the endometrium to NK cytotoxicity.
Arangia A et al., 2023·Int J Mol Sci·Free full text on PubMed Central
A chronic, painful, and inflammatory condition known as endometriosis is defined by the extra-uterine development of endometrial tissue. The aim of this study was to evaluate the beneficial effects of fisetin, a naturally occurring polyphenol that is frequently present in a variety of fruits and vegetables. Uterine fragments were injected intraperitoneally to cause endometriosis, and fisetin was given orally every day. At 14 days of treatment, laparotomy was performed, and the endometrial implants and peritoneal fluids were collected for histological, biochemical, and molecular analyses. Rats subjected to endometriosis presented important macroscopic and microscopic changes, increased mast cell (MC) infiltration, and fibrosis. Fisetin treatment reduced endometriotic implant area, diameter, and volumes, as well as histological alterations, neutrophil infiltration, cytokines release, the number of MCs together with the expression of chymase and tryptase, and diminished α smooth muscle actin (α-sma) and transforming growth factor beta (TGF β) expressions. In addition, fisetin was able to reduce markers of oxidative stress as well as nitrotyrosine and Poly ADP ribose expressions and increase apoptosis in endometrial lesions. In conclusion, fisetin could represent a new therapeutic strategy to control endometriosis perhaps by targeting the MC-derived NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome pathway and oxidative stress.
Lete I et al., 2018·European journal of obstetrics, gynecology, and reproductive biology
To assess the impact of an antioxidant preparation with N-acetyl cysteine, alpha lipoic acid and bromelain on endometriosis-associated pelvic pain. Multicenter, open-label, non-comparative clinical trial in a representative sample of women with endometriosis-associated pelvic pain. In total, 398 patients with a mean age of 34.6 ± 7.2 years were treated with a combination of N-acetyl cysteine, alpha lipoic acid and bromelain for 6 months. At baseline, 92.7% of the patients had pain intensity > 4 on the visual analogue scale (VAS); at 3 months of treatment, this percentage decreased to 87.2% (p = 0.074) and at 6 months the percentage was 82.7% (p < 0.05). Women with endometriosis who wish to become pregnant and are treated with a preparation containing N-acetyl cysteine, alpha lipoic acid and bromelain experienced a significant improvement in endometriosis-associated pelvic pain and required lower intake of rescue analgesics.
Endometriosis › Medical Management › Pain Management · Therapeutics › Supplements and Botanicals › Antioxidant Supplements · General Gynecology › Pelvic Pain › Chronic Pelvic Pain
R De Leo, F De Seta
PMID 25960622 25960622 DOI 10.1155/2015/918089 10.1155/2015/918089 Agostinis et al. 2015, Agostinis 2015
Cite this article
Agostinis, C., Zorzet, S., De Leo, R., Zauli, G., De Seta, F., & Bulla, R. (2015). 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. Mediators of inflammation, 2015(1), 918089. https://doi.org/10.1155/2015/918089
Agostinis C, Zorzet S, De Leo R, Zauli G, De Seta F, Bulla R. 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. Mediators Inflamm. 2015;2015(1):918089. doi:10.1155/2015/918089
Agostinis, Chiara, et al. "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." Mediators of inflammation, vol. 2015, no. 1, 2015, pp. 918089.
