This study reveals the existence of oxidative stress (reactive oxygen species (ROS)) in non-nervous organs and tissues in multiple sclerosis (MS) by means of a model of experimental autoimmune encephalomyelitis (EAE) in rats. This model reproduces a similar situation to MS, as well as its relationship with intestinal microbiota starting from the changes in bacterial lipopolysaccharide levels (LPS) in the outer wall of the gram-negative bacteria. Finally, the administration of extra-virgin olive oil (EVOO), hydroxytirosol (HT), and oleic acid (OA) exert beneficial effects. Twenty-five Dark Agouti two-month-old male rats, weighing around 190 g, were distributed into the following groups: Control, EAE (experimental autoimmune encephalomyelitis group), EAE + EVOO, EAE + HT, and EAE + OA. The glutathione redox system with the EAE was measured in heart, kidney, liver, and small and large intestines. The LPS and the correlation with oxidative stress in the small and large intestines were also investigated. The results showed that (1) the oxidative damage in the EAE model affects non-nervous organs and tissues; (2) The LPS is related to inflammatory phenomena and oxidative stress in the intestinal tissue and in other organs; (3) The administration of EVOO, HT, and OA reduces the LPS levels at the same time as minimizing the oxidative damage; (4) EVOO, HT, and OA improve the disease’s clinical score; and (5) on balance, EVOO offers a better neuroprotective effect.

Background: Multiple sclerosis (MS) is an autoimmune neurodegenerative disease with a higher prevalence in women. While puberty appears to act as a trigger for MS, menopause has no clear effects on disease progression. Many studies have shown that transcranial magnetic stimulation (TMS) is a potential antioxidant treatment for MS, but the sexual hormones have been identified as a potential factor affecting TMS response by affecting cortical excitability and possibly clinical outcomes. Methods: The aim of this study was to test the effect of estrogen, progesterone, and testosterone hormonal supplementation as adjuvants to TMS treatment of experimental autoimmune encephalomyelitis (EAE), an experimental model of MS. The effects of the three hormones were also tested as replacement therapy in ovariectomized rats treated with TMS. Clinical signs of the disease, as well as disease-induced oxidative stress and antioxidant defenses of the glutathione system, were evaluated. Results: TMS alone, without supplements or replacement therapies, is effective against oxidative stress caused by EAE. Estrogen and progesterone replacement therapy is useful to enhance the role of TMS in ovariectomized rats, activating antioxidant defenses and improving clinical signs of the disease. Conclusions: TMS is effective in the treatment of MS, but its role could be enhanced, using hormone replacement therapy with estrogens and/or progesterone.

Transcranial magnetic stimulation (TMS) is a non-invasive brain stimulation method with neuromodulatory capacity in neurodegenerative diseases such as multiple sclerosis (MS). Its therapeutic value is linked to its activity against oxidative stress by activation of antioxidant defenses. The sex hormones, estrogens (E), progesterone (P) and testosterone (T), have demonstrated their power as adjuvants to TMS, improving cortical excitability. The aim of this study was to evaluate the effect of these hormones as adjuvants to extremely low-frequency electromagnetic fields (ELFEFs) in the treatment of experimental autoimmune encephalomyelitis (EAE), the experimental model of MS. The effect of these hormones as replacement therapy was also evaluated in ovariectomized rats treated with ELFEFs. Sixty-five female Dark Agouti rats were divided into 13 groups (5 rats/group), in which biomarkers of oxidative stress and the glutathione redox cycle in non-nervous organs (kidney, liver, heart, intestines and blood) were analyzed. The results show that ELFEFs alone are more effective against oxidative stress. However, P and E were more effective than ELFEFs, both as adjuvants and in hormone replacement therapy, in activating the glutathione system. Therefore, it could be concluded that sex hormones play an important role against MS, enhancing the antioxidant effect of ELFEFs.