Oxidative stress

Oxidative stress is the state in which a cell produces more reactive oxygen species than its antioxidant systems can neutralise, so the surplus reacts with lipids, proteins, and DNA and damages them. It is a matter of balance rather than of the presence of reactive species: those molecules are made continuously and are needed for normal signalling.

Where the reactive species come from

Most arise as a by-product of energy production. Electrons leaking from the transport chain in the mitochondria react with oxygen to form superoxide. Immune cells make more of them deliberately — the respiratory burst that kills engulfed bacteria. Ultraviolet light, pollutants, heavy metals, and some drugs add to the load.

The main species are superoxide, hydrogen peroxide, the hydroxyl radical, and peroxynitrite. Hydrogen peroxide is comparatively stable and doubles as a signalling molecule; the hydroxyl radical reacts with whatever it touches first.

The defences

• Superoxide dismutase converts superoxide to hydrogen peroxide.
• Catalase and glutathione peroxidase convert hydrogen peroxide to water.
• Glutathione, the most abundant intracellular antioxidant, is the reducing agent those enzymes spend and regenerate.
• Vitamins C and E intercept radicals in aqueous and lipid compartments respectively, and are themselves regenerated by glutathione.
• NRF2, a transcription factor, senses oxidation and turns up the whole set.

What the damage looks like

Lipid peroxidation stiffens and perforates membranes; oxidised proteins lose function and aggregate; oxidised DNA bases cause mutations. Sustained oxidative stress is linked with atherosclerosis, neurodegeneration, chronic inflammation, and the accumulation of senescent cells.

Why more antioxidant is not automatically better

Reactive oxygen species are part of normal signalling — including the adaptive response to exercise. Several large trials of high-dose antioxidant supplements found no benefit, and some found harm. Suppressing the signal can blunt the adaptation it was meant to protect.

Why peptides care

• Glutathione is the central endogenous antioxidant itself, taken orally, intravenously, or by injection for antioxidant and liver support. It is one of the few compounds catalogued here that is permitted under WADA rules as a substance, though intravenous infusion above the volume limit of WADA method M2.2 is restricted whatever is infused.
• BPC-157 is reported in preclinical tendon work to improve cell survival under oxidative stress, alongside its broader cytoprotective profile.

Related concepts

The organelles that generate most reactive species are covered in mitochondria; the coenzyme that supports part of the antioxidant machinery has its own article at NAD+.