Hidrox® and Endometriosis: Biochemical Evaluation of Oxidative Stress and Pain

Abstract

Endometriosis is a gynecological and painful condition affecting women of reproductive age. It is characterized by dysfunctional endometrium-like implants outside of the uterine cavity. The purpose of this study was to evaluate the effects of Hidrox®, an aqueous extract of olive pulp containing hydroxytyrosol, on endometriotic lesions associated with pro-oxidative alterations and pain-like behaviors. Endometriosis was induced by intraperitoneal injection of uterine fragments, and Hidrox® was administered daily. At the end of the 14-day treatment, behavioral alterations were assessed and hippocampal tissues were collected. Laparotomy was performed, and the endometrial implants were harvested for histological and biochemical analysis. Hidrox® treatment reduced endometriotic implant area, diameter and volumes. Vehicle-treated rats showed lesional fibrosis, epithelial–mesenchymal transition and fibroblast–myofibroblast transdifferentiation, angiogenesis and pro-oxidative alterations in the peritoneal cavity. Hidrox® treatment reduced the aniline blue-stained area, α-smooth muscle actin (α-sma) and CD34 positive expressions. Moreover, it reduced mast cell recruitment into the lesions, myeloperoxidase activity and lipid peroxidation and increased superoxide dismutase (SOD) activity and glutathione levels in the endometrial explants. In the peritoneal fluid, Hidrox® treatment reduced interleukin (IL)-1β, IL2, IL6, tumor necrosis factor-α (TNF-α) and vascular endothelial grow factor (VEGF) levels increased by the disease. Hidrox® administration also reduced peripheral and visceral sensibility as shown by the behavioral tests (open field test, hot plate test, elevated plus maze test and acetic-acid-induced abdominal contractions). Animals treated with Hidrox® also showed reduced blood–brain barrier permeability and mast cell infiltration in the hippocampus, as well as astrocyte and microglia activation and brain oxidative status restoring brain-derived neurotrophic factor (BDNF) protein expression and increasing Nuclear factor erythroid 2-related factor 2 (Nfr2) nuclear translocation. In conclusion, Hidrox® displayed potential ameliorative effects on endometriotic implants and related pain-induced behaviors due to its potent antioxidative properties.

The effects of adalimumab on the rat autotransplantation endometriosis model: A placebo-controlled randomized study

“…28 It has been hypothesized that eliminating oxidative stress may reduce the histopathological grade in endometrial implants and many studies have been conducted on this subject. 27,29,30 Proinflammatory cytokines such as IL-1, IL-6, IL-8, and TNF-α have also been shown to play a role in the pathology of endometriosis. 31 It has been demonstrated that there is an increase in TNF-α levels in the peritoneal fluids of women with endometriosis.…”

Wnt/β-Catenin Pathway in Experimental Model of Fibromyalgia: Role of Hidrox®

“…Additionally, ROS overproduction by microglia is suggested to be a main cause of neuronal damage and dysfunction inducing derangement of neuronal redox signaling circuits or direct oxidative damage [27,48]. Much evidence supports the role of oxidative stress in the progress of FM [5,49].…”

“…The dose and route of HD treatment were chosen based on previous studies [26][27][28]. At the end of the experiment, the L4-L6 region of the spinal cord from each rat was collected for all analyses.…”

Unveil the pain of endometriosis: from the perspective of the nervous system

“…149). The formation of an immune oxidative environment within the hippocampus of endometriosis rats is one of the mechanisms leading to pain sensitisation, whereas the elevated oxidative state in the hippocampus was correlated with a lower level of BDNF (Refs 150, 151). Astrocytes and microglia are thought to be responsible for many inflammatory processes in affected brains, including secretion of inflammatory mediators and stimulation of the innate immune system (Ref.…”