Definition of Oxidative Stress

How is oxidative stress generated?

The organisms Aerobes use oxygen to fulfill their biological functions through enzymatic and non-enzymatic reactions. The mitochondria is an organelle where oxygen is consumed by reducing it to water, generating chemical species. unstable and therefore reactive like free radicals, which tend to oxidize cell structures (biomolecules). In the presence of this basal oxidant system, there is a basal antioxidant defense system made up of enzymes and other proteins that eliminate, delay and/or prevent the generation and accumulation of reactive species and that are generally found in lower concentration than pro-oxidant molecules.

When the oxidizing system overwhelms the antioxidant system, it is said that the

cell enters into stress, since the main biomolecules such as DNA, proteins and lipids tend to be targets of reactive molecules, generating an imbalance in the homeostasiscell phone and therefore cell injury characterized by edema (swelling) and vacuolization, this type of injury is reversible, however, when the oxidative insult is unsustainable, it leads to irreversible injury resulting in death of the plant. cell.

Another source of generation of reactive molecules is from cells of the immune response (neutrophils and macrophages) whose activation leads to the generation of these molecules, mainly during processes inflammatory.

reactive molecules

The main reactive molecules are those derived from oxygen, since they are the most abundant in biological systems and which are commonly known as reactive oxygen species (ROS) and which includes both free and non-free radicals. radicals. Free radicals are chemical species that have been removed or donated a hydrogen atom or a electron, which gives it instability and therefore high reactivity since they will seek to gain stability by stealing or donating an atom of hydrogen or electron to another chemical species converting it into a free radical and in this way trigger reactions of oxidation-reduction. Non-radical reactive species are stable molecules, however they favor the oxidation of other atoms or molecules, such as hydrogen peroxide ((H₂EITHER₂).

The ROS that stand out the most are the superoxide anion (O2^•-), which is the first metabolic product of oxidative phosphorylation generated in the mitochondria; the hydroxyl radical (^•OH) that is generated from the Fenton reaction, which occurs in the presence of hydrogen peroxide and transition metals such as iron; hydrogen peroxide (H₂EITHER₂) that is generated as a product of the activity of the enzyme superoxide dismutase on the superoxide anion (O2^•-); the hydroperoxide (ROOH) which is the product of the oxidation of biomolecules.

Also, there are molecules that function as messengers in the transduction of cellular signals, as is the case of nitric oxide (NO) that at moderate concentrations it fulfills various physiological functions, but that when there is an increase in oxidative stress, it can generate other reactive species known as reactive nitrogen species (ERN) such as peroxynitrine (ONOO-)

There are different diseases that are generated from the increase in oxidative stress caused by different stimuli. Among the most studied are cancer, cardiovascular, neurological, respiratory disease, arthritis rheumatoid disease, liver and kidney toxicity, among others, however, it continues to be a field with a lot of scope for explore.

Biotransformation of xenobiotics

All the substances that we consume or to which we are exposed enter our system through different routes (inhaled, oral, sublingual, tonic, intramuscular, intravenous, intraperitoneal, intragastric) and are sent into the bloodstream where they are distributed to all compartments of the our body, passing through the liver, which is the main metabolizing organ of xenobiotics (substances that enter our system and come from the Exterior).

Among its functions, the liver has the ability to biotransform xenobiotics, that is, it changes the chemical structure of the compound through various oxidation and conjugation reactions in order to obtain a more water-soluble product, which favors its elimination. However, during these chemical modifications, reactive metabolites are generated which, depending on the magnitude of the exposition, can cause an increase in oxidative stress. Exposure can be acute (high doses/concentrations) or chronicle (for a long period of time). The xenobiotics that most commonly cause liver toxicity (hepatotoxicity) are Non-Steroidal Anti-Inflammatory Drugs (NSAIDs).