Achieving the balance between ROS and antioxidants: when to use the synthetic antioxidants

Abstract

Free radical damage is linked to formation of many degenerative diseases, including cancer, cardiovascular disease, cataracts, and aging. Excessive reactive oxygen species (ROS) formation can induce oxidative stress, leading to cell damage that can culminate in cell death. Therefore, cells have antioxidant networks to scavenge excessively produced ROS. The balance between the production and scavenging of ROS leads to homeostasis in general; however, the balance is somehow shifted towards the formation of free radicals, which results in accumulated cell damage in time. Antioxidants can attenuate the damaging effects of ROS in vitro and delay many events that contribute to cellular aging. The use of multivitamin/mineral supplements (MVMs) has grown rapidly over the past decades. Some recent studies demonstrated no effect of antioxidant therapy; sometimes the intake of antioxidants even increased mortality. Oxidative stress is damaging and beneficial for the organism, as some ROS are signaling molecules in cellular signaling pathways. Lowering the levels of oxidative stress by antioxidant supplements is not beneficial in such cases. The balance between ROS and antioxidants is optimal, as both extremes, oxidative and antioxidative stress, are damaging. Therefore, there is a need for accurate determination of individual's oxidative stress levels before prescribing the supplement antioxidants.

Figure 1

Model antioxidative/oxidative balance of an adult person—the balance is slightly moved towards the increased ROS production (dashed line). The physiological balance is represented by the dashed line and not the dotted line (geometrical balance), since slight pro-oxidative balance is necessary for optimal immune system and cell signaling processes.

Figure 2

Oxidative stress due to severe disturbance between ROS formation and antioxidative defenses (the physiological balance is represented by the dashed line).

Figure 3

Severe disturbance between antioxidative defenses and ROS leads to a state of increased “antioxidative stress.”

Figure 4

The optimal situation: the physiological balance between the ROS production and antioxidative defenses prevents the accumulation of damage by ROS and enables enough ROS for signaling. Enzymatic and nonenzymatic antioxidants can neutralize ROS and RNS and decrease oxidative stress and restore the balance.

Scheme 1

Methods of oxidative stress determination. (8-OHG) = 8-hydroxyguanosine; 4-HNE = 4-Hydroxynonenal; MDA = malondialdehyde; PCC = protein carbonyl content; AGE = advanced glycation end products; AOPP = advanced oxidation protein products.

Scheme 2

Oxidative and “antioxidative” stress: causes, consequences and methods for its control.