The role of oxidative stress in thepathogenesis of multiple sclerosis: The need for effectiveantioxidant therapy

Abstract. Accumulating data indicate that oxidative stress (OS)plays a major role in the pathogenesis of multiple sclerosis(MS). Reactive oxygen species (ROS), leading to OS, generated inexcess primarily by macrophages, have been implicated asmediators of demyelination and axonal damage in both MS andexperimental autoimmune encephalomyelitis (EAE), its animalmodel. ROS cause damage to cardinal cellular components such aslipids, proteins and nucleic acids (e. g., RNA, DNA), resultingin cell death by necrosis or apoptosis. In addition, weakenedcellular antioxidant defense systems in the central nervoussystem (CNS) in MS, and its vulnerability to ROS effects mayincrease damage. Thus, treatment with antioxidants mighttheoretically prevent propagation of tissue damage and improveboth survival and neurological outcome. Indeed, severalexperimental studies have been performed to see whether dietaryintake of several antioxidants prevents or reduces theprogression of EAE. Although a few antioxidants showed someefficacy in these studies, little information is available onthe effect of treatments with such compounds in patients withMS. Well-designed clinical studies using antioxidant intake, aswell as investigations based on larger cohorts studied over alonger periods of time, are needed in order to assess whetherantioxidant intake together with other conventional treatments,might be beneficial in treating MS.