Total Oxidative Stress (TOS) reflects the overall burden of oxidant molecules circulating in the body and is considered one of the most important indicators of the body's redox balance. A central role in its generation is played by Reactive Oxygen Species (ROS), which are naturally produced during normal cellular metabolism and participate in essential physiological processes, including cell signaling and host defense against invading pathogens.
The term Reactive Oxygen Species (ROS) describes several reactive molecules and free radicals derived from molecular oxygen. The production of oxygen-based radicals is the bane of all aerobic species. These molecules, produced as byproducts during mitochondrial electron transport in aerobic respiration or by oxidoreductase enzymes and metal-catalyzed oxidation, can cause several deleterious effects. It was initially thought that only phagocytic cells were responsible for ROS production as part of host cell defense mechanisms. Recent work has demonstrated that ROS play a role in cell signaling, including apoptosis, gene expression, and activation of signaling cascades. It should be noted that ROS can serve as both intra- and intercellular messengers.
Detoxification of reactive oxygen species is paramount to the survival of all aerobic life forms. As such, several defense mechanisms have evolved to meet this need and to balance the production and removal of ROS. An imbalance toward the pro-oxidative state is often referred to as “Oxidative stress.”
Cells have a variety of defense mechanisms to ameliorate the harmful effects of ROS. Superoxide dismutase (SOD) catalyzes the conversion of two superoxide anions into a molecule of hydrogen peroxide (H2O2) and oxygen (O2). In the peroxisomes of eukaryotic cells, the enzyme catalase converts H2O2 to water and oxygen, thereby completing the detoxification initiated by SOD. Glutathione peroxidase is a group of selenium-containing enzymes that catalyze the degradation of hydrogen peroxide and organic peroxides to alcohols.
Several small-molecule antioxidants, not enzymes, play a role in detoxification. Glutathione may be the most important intracellular defense against the deleterious effects of reactive oxygen species. Vitamin C, or ascorbic acid, is a water-soluble molecule capable of reducing ROS, while vitamin E (α-tocopherol) is a lipid-soluble molecule that has been suggested as playing a similar role in membranes.
ROS and Diseases
Researchers have been trying to elucidate the mechanisms and roles of ROS in disease since their identification. ROS influence diseases mainly through their roles as signaling molecules and oxidants that affect cell survival and oxidative damage. ROS could also drive immunity through immunological defense and maintain metabolic balance or heat dissipation.
ROS can function as intermediates in varying pathways, but they are also widely regarded as etiologic factors for diseases, including cancer, inflammation, and organ injuries. Evidence suggests that scavenging ROS in pathological conditions may reduce cell damage and control the pathological process.
The ROS have both positive and negative impacts on various diseases:
- Cancer positive impact: Impair tumorigenesis, apoptosis
- Cancer negative impact: High metastasis, canceration, radioresistance, carcinogenesis
- Inflammatory diseases' positive impact: Prevent experimental autoimmune encephalomyelitis, support the immune system, and macrophage killing
- Inflammatory diseases' negative impact: Inflammatory bowel diseases, parasite-caused organic damage, periodontitis, tendinopathy, bronchitis, emphysema, rheumatoid arthritis
- Neurologic diseases' positive impact: Synaptic plasticity, neuronal development
- Neurologic diseases' negative impact: Movement disorder, neuron apoptosis, neurotoxicity, retardation
- Vascular diseases' positive impact: Relaxation of cerebral arteries, blood flow homeostasis, and wound repair
- Vascular diseases negative impact: Hypertension, vascular injury, ischemia-reperfusion damage, retinal dysfunction, pneumoconiosis, atherosclerosis, and acute respiratory distress syndrome
- Organ failure positive impact: Respiratory plasticity, sensory plasticity
- Organ failure negative impact: Liver failure, renal failure, heart failure
- Diabetes's negative impact: Insulin resistance
- Aging positive impact: Muscle cell development, muscle remodeling
- Aging negative impact: Sarcopenia, muscular dystrophy, DNA damage
- Infertility's negative impact: Damage to spermatogenesis, ovarian toxicity
