We propose that a molecular link between the exaggerated dysfunctional repair response in overuse tendinopathies and the subsequent orchestration of effective tendon healing is the control of the production and persistence of reactive oxygen species within the intracellular and extracellular milieu of the tendon tissue. Reactive oxygen production and the ensuing cellular response can be strongly influenced by lifestyle factors such as the intensity and frequency of exercise.

“Reactive oxygen species” (ROS; also referred to as active oxygen species, AOS; reactive oxygen intermediates, ROI) is a collective term for both radical and non-radical but reactive species derived from oxygen. A free radical, is “any species capable of independent existence that contains one or more unpaired electrons”.¹ The presence of such unpaired electron(s) often imparts considerable reactivity. Commonly detected and potentially physiologically relevant ROS include the superoxide anion, hydrogen peroxide (H₂O₂), the hydroxyl radical, singlet oxygen, and peroxyl radicals. A further and inter-related group are the reactive nitrogen species (RNS)—for example, peroxynitrite.¹

ROS are continually produced during normal cell metabolism. The mitochondrial respiratory chain, NADPH-cytochrome P₄₅₀ enzymes in the endoplasmic reticulum, phagocytic cells, lipoxygenase, and cyclo-oxygenase are also sources of basal ROS production.¹ Trauma and environmental and physiological stimuli may enhance ROS production.¹

Traditionally, ROS are viewed as imposing cellular/tissue damage through lipid peroxidation, protein modification, DNA strand cleavage, and oxidative base modification, although the relative reactivity and susceptibility of the molecular targets vary. Thus, ROS production is implicated in numerous aspects of pathophysiology including tumorigenesis, coronary heart disease, autoimmune disease, overuse exercise related damage to muscle, and impairment of fracture healing.^1,2

This association with cellular damage and pathology has predisposed much of the literature to consider decreased …