Oxidative Stress and Nitrosative Stress: Complications

The following are the major sequelae that may be contributed to by oxidative stress or nitrosative stress:

Oxidative stress has effects on:

  • Mitochondria (“power plants of the cells”) (see below for nitrosative stress).
  • Enzymes (“metabolic accelerators”; enzymes of the citric acid cycle, the respiratory chain, and biotin synthase, which have iron as a cofactor, lose their functionality due to oxidants that release iron to the outside)
  • Vessels (see below for hypertension / high blood pressure).
  • Neurons
    • Disruption of mitochondrial function → limitation of energy production within the neuron → limitation of axonal transport of cell structural proteins.
    • Impairment of excitation conduction (due to stress-induced damage to membrane and protein structures of neurons) → neurodegenerative diseases.

Nitrosative stress has effects on:

Mitochondria

  • Nitric oxide radical (NO.) reversibly inhibits cytochrome C oxidase, an enzyme of the mitochondrial respiratory chain. This effect is physiological and serves to control oxidative phosphorylation, i.e., ATP synthesis. In case of a strong increase of superoxide radicals (O2-.) NO. combines with O2-. and the extremely cytotoxic peroxynitrite anion (ONOO-) is formed, which irreversibly inhibits cytochrome C oxidase! This results in irreversible damage to energy production. Consequently, it comes by O2-. and ONOO- to the destruction of the inner mitochondrial membrane and thus to the cell death.

Free radicals damage the further:

  • Elastin
  • Fatty acids; lipids from which cell membranes and other organelles such as mitochondria as well as lysosomes (cell organelles) are built are oxidized, this is called lipid peroxidation (oxidative degradation of lipids)
  • Carbohydrates
  • Collagen
  • Mucopolysaccharides (components of many biological macromolecules).
  • Proteins – oxidation of proteins

Furthermore, the free radicals also react with the cell nucleus and DNA (genetic information). The result of this oxidative DNA damage are, for example, point mutations and enzyme disorders, which lead to significant disruption of cellular functions and thus metabolic processes. ROS-related mutations also increase with age. This particularly affects the mitochondria.Free radicals increase the risk of numerous diseases:

Eyes and eye appendages (H00-H59).

  • Cataract (cataract)

Blood, blood-forming organs – immune system (D50-D90).

  • Autoimmune diseases, unspecified
  • Immune system disorders

Endocrine, nutritional and metabolic diseases (E00-E99).

Cardiovascular system (I00-I99).

  • Apoplexy (stroke)
  • Atherosclerosis (arteriosclerosis; hardening of the arteries)
  • Coronary heart disease (CHD)
  • Myocardial infarction (heart attack)

Infectious and parasitic diseases (A00-B99).

  • Inflammation, unspecified

Mouth, esophagus (food pipe), stomach, and intestines (K00-K67; K90-K93).

Musculoskeletal system and connective tissue (M00-M99).

  • Rheumatic diseases

Neoplasms – tumor diseases (C00-D48)

  • Tumor diseases

Psyche – nervous system (F00-F99; G00-G99)

Genitourinary system (N00-N99)

  • Male subfertility (attributed to oxidative stress in 30-80% of cases) Oxidative stress and male infertility see below.

Further

  • Aging processes

However, free radicals are not only harmful metabolic products. They also have their good sides: For example, they serve the immune defense, because granulocytes and macrophages (phagocytes) harness the effect of free radicals by destroying bacteria with their help. Another important role free radicals probably play in apoptosis (programmed cell death) this is important for the endogenous suppression of tumor diseases.

Pro oxidative stress!

  • Reactive oxygen species (ROS) led to extended lifespan in studies of various model organisms:
    • ROS serve as a signal for endogenous defense mechanisms → results in increased stress resistance and lifespan.

Free Radical Theory of Aging (FRTA) vs Mitohormesis.

  • Free Radical Theory of Aging (FRTA)
  • Free radicals are the cause of the aging process (Harman, 1956).
  • Damage to cells, DNA or lipids causes the complex aging process.
  • Hormesis (Greek : “stimulation”, “impetus”).
  • Small doses of harmful substances can have a positive effect on the organism (Paracelsus, 1493 – 1541).

Physiological formation (eg, sports) of free radicals in the mitochondria favors health-promoting effects in the organism.

Are antioxidants now superfluous?

  • Maintaining a balance of prooxidant and antioxidant processes.
  • Physiological influence of antioxidants necessary
  • Micronutrients (vital substances) in the low dose range up to 3 times RDA (Recommended Dietary Allowances) are safe in terms of negative suppression of oxidative stress! (Positive effects of oxidative stress are not suppressed in this dose range).