Dimethyl Fumarate Alleviates Dextran Sulfate Sodium-Induced Colitis, through the Activation of Nrf2-Mediated Antioxidant and Anti-inflammatory Pathways.

Oxidative stress and chronic inflammation play critical roles in the pathogenesis of ulcerative colitis (UC) and inflammatory bowel diseases (IBD). A previous study has demonstrated that dimethyl fumarate (DMF) protects mice from dextran sulfate sodium (DSS)-induced colitis via its potential antioxidant capacity, and by inhibiting the activation of the NOD-, LRR- and pyrin domain-containing protein 3 (NLRP3) inflammasome. This study aims to clarify the nuclear factor erythroid 2-related factor 2/antioxidant responsive element (Nrf2/ARE) pathway pharmacological activation and anti-inflammatory effect by DMF, through focusing on other crucial antioxidant enzymes and inflammatory mediator, including glutamate-cysteine ligase catalytic subunit (GCLC), glutathione peroxidase (GPX) and cyclooxygenase-2 (COX-2), in a DSS-induced colitis mouse model. The oral administration of DMF attenuated the shortening of colons and alleviated colonic inflammation. Furthermore, the expression of key antioxidant enzymes, including GCLC and GPX, in the colonic tissue were significantly increased by DMF administration. In addition, protein expression of the inflammatory mediator, COX-2, was reduced by DMF administration. Our results suggest that DMF alleviates DSS-induced colonic inflammatory damage, likely via up-regulating GCLC and GPX and down-regulating COX-2 protein expression in colonic tissue

Endogenous Antioxidants: A Review of their Role in Oxidative Stress

Oxidative stress (OxS) constitutes a disturbance caused by an imbalance between the generation of free radicals and antioxidant system, which causes damage to biomolecules. This, in turn, may lead the body to the occurrence of many chronic degenerative diseases. Therefore, it is very important to know the functioning of those endogenous (and exogenous) antioxidants systems to prevent such diseases. Due to evolutionary conditions in living beings, among other functions have been developed and selected defense systems against the deleterious action of free radicals. Such systems are intrinsic in cells (at level intracellular and extracellular) and act together with the dietary exogenous antioxidants. All these antioxidant systems have very important role in preserving the oxide/reduction equilibrium in the cell. To understand the role of the transcription factor Nrf2 in regulating the processes of antioxidant defense, it must also know the role of many of the endogenous antioxidants that occur because of its activation. Therefore, this chapter makes a literature review of the most important general aspects of endogenous antioxidant systems, which will provide another point of view from which to approach the study and treatment of many chronic degenerative diseases, such as diabetes, hypertension, and Parkinson