Potential Antioxidant Multitherapy against Complications Occurring in Sepsis

Abstract

Septic shock currently represents one of the main causes of mortality in critical patient units with an increase in its incidence in recent years, and it is also associated with a high burden of morbidity in surviving patients. Within the pathogenesis of sepsis, oxidative stress plays an important role. The excessive formation of reactive oxygen species (ROS) leads to mitochondrial damage and vasomotor dysfunction that characterizes those patients who fall into septic shock. Currently, despite numerous studies carried out in patients with septic shock of different causes, effective therapies have not yet been developed to reduce the morbidity and mortality associated with this pathology. Despite the contribution of ROS in the pathophysiology of sepsis and septic shock, most studies performed in humans, with antioxidant monotherapies, have not resulted in promising data. Nevertheless, some interventions with compounds such as ascorbate, N-acetylcysteine, and selenium would have a positive effect in reducing the morbidity and mortality associated with this pathology. However, more studies are required to demonstrate the efficacy of these therapies. Taking into account the multifactorial features of the pathophysiology of sepsis, we put forward the hypothesis that a supplementation based on the association of more than one antioxidant compound should result in a synergistic or additive effect, thus improving the beneficial effects of each of them alone, potentially serving as a pharmacological adjunct resource to standard therapy to reduce sepsis complications. Therefore, in this review, it is proposed that the use of combined antioxidant therapies could lead to a better clinical outcome of patients with sepsis or septic shock, given the relevance of oxidative stress in the pathogenesis of this multi-organ dysfunction.

Keywords: antioxidants; multitherapies; oxidative stress; sepsis; septic shock.

Figure 1

Schematization of oxidative stress mediated endothelial and mitochondrial dysfunction in sepsis pathogenesis, and antioxidant protection. eNOS: endothelial nitric oxide synthase; GSH: glutathione; GSH-Px: glutathione peroxidase; iNOS: induced nitric oxide synthase; LPO: lipid peroxidation; NAC: n-acetylcysteine; NOX: NADPH oxidase; ROS: reactive oxygen species; Se: selenium; uNOS: uncoupled nitric oxide synthase; Vit C: vitamin C; Vit E: vitamin E.