Efforts Towards Repurposing of Antioxidant Drugs and Active Compounds for Multiple Sclerosis Control.

Multiple Sclerosis (MS) is a degenerative disorder of the central nervous system (CNS) with complicated etiology that has not been clearly analyzed until nowadays. Apart from anti-inflammatory, immune modulatory and symptomatic treatments, which are the main tools towards MS control, antioxidant molecules may be of interest. Oxidative stress is a key condition implicated in the disease progression. Reactive species production is associated with immune cell activation in the brain as well as in the periphery, accounting for demyelinating and axonal disruptive processes. This review refers to research articles, of the last decade. It describes biological evaluation of antioxidant drugs, and molecules with pharmaceutical interest, which are not designed for MS treatment, however they seem to have potency against MS. Their antioxidant effect is accompanied, in most of the cases, by anti-inflammatory, immune-modulatory and neuroprotective properties. Compounds with such characteristics are expected to be beneficial in the treatment of MS, alone or as complementary therapy, improving some clinical and mechanistic aspects of the disease. This review also summarizes some of the pathobiological characteristics of MS, as well as the role of oxidative stress and inflammation in the progression of neurodegeneration. It presents known drugs and bioactive compounds with antioxidant, and in many cases, pleiotropic activity that have been tested for their efficacy in MS progression or the experimentally induced MS. Antioxidants may offer reduction or prevention of the disease symptoms and progression. Thus, their results may, combined with already applied treatments, be beneficial for the development of new molecules or the repurposing of drugs and supplements that are used with other indication so far.

[Pathophysiological mechanisms of major mental disorders related to cardiovascular disease].

Although the relationship of mental health with cardiovascular dysfunction is not a recent finding, scientific data has appeared approximately at the middle of the last century. Firstly, depression was studied as a risk factor for premature death in cases of cardiovascular disease (CVD). Much later, the mechanism of psychosis and schizophrenia in the development of CVD were studied, as it was observed that most premature deaths in schizophrenia were related to cardiovascular disease. This interaction is supported both by epidemiological data and by the associated mechanisms. Inflammation, oxidative and biologic stress, and hormonal and neurotransmitter disorders in coagulation, tissue perfusion, vascular dysfunction and genetic factors get involved in these mental disorders. The combination of these pathophysiological mechanisms and the general risk factors for CVD (sex, age, smoking, systolic blood pressure, body weight, glucose levels) leads, to some extent, to increased rates of comorbidity and mortality. Patients with severe mental disorders are often not monitored and do not receive appropriate treatment for cardiovascular risk factors. In studies of patients with comorbid coronary heart disease and depression, there were signs of cardiovascular dysfunction, including increased heart rate, mainly in stress, QT prolongation and ventricular arrhythmia. At the same time, there is a dose-response relationship between the severity of depression and cardiovascular risk, with the presence of even mild symptoms of untreated depression involving some cardiovascular risk. In addition, improving the symptoms of depression through medication has been associated with increased survival. Moreover, the causes of increased mortality in patients with schizophrenia are similar to those of the general population with metabolic syndrome and diabetes mellitus, while failure to receive antipsychotic medication could lead to obesity, insulin resistance, dyslipidemia and hypertension. These data could be used as a source for future anti-inflammatory therapeutic approaches, but also for the appropriate selection of therapeutic agents, by taking a more holistic view of the patient's comorbidity. The interdisciplinary collaboration and liaison - consultation psychiatry are important factors for the timely prevention, recognition and treatment of potent complications of the cardiovascular system in mentally ill patients. The aim of this review was to present the pathophysiological mechanisms of serious mental disorders, such as depression, bipolar disorder, and schizophrenia that may be related to the development of CVD.

Lipoic acid. Kinetics and pluripotent biological properties and derivatives.

Lipoic acid (LA) is globally known and its supplements are widely used. Despite its importance for the organism it is not considered a vitamin any more. The multiple metabolic forms and the differences in kinetics (absorption, distribution and excretion), as well as the actions of its enantiomers are analysed in the present article together with its biosynthetic path. The proteins involved in the transfer, biotransformation and activity of LA are mentioned. Furthermore, the safety and the toxicological profile of the compound are commented, together with its stability issues. Mechanisms of lipoic acid intervention in the human body are analysed considering the antioxidant and non-antioxidant characteristics of the compound. The chelating properties, the regenerative ability of other antioxidants, the co-enzyme activity and the signal transduction by the implication in various pathways will be discussed in order to be elucidated the pleiotropic effects of LA. Finally, lipoic acid integrating analogues are mentioned under the scope of the multiple pharmacological actions they acquire towards degenerative conditions.