Oxidative stress explained
Reactive Oxygen Species
Organisms that live under aerobic conditions depend on oxygen for respiration. Although respiration is essential for life and necessary to generate energy, it is also harmful due to the formation of reactive oxygen species (ROS). ROS are highly reactive compounds derived from oxygen capable of damaging cellular macromolecules such as DNA, proteins and lipids. Examples of ROS include hydroxyl radical, superoxide, hydrogen peroxide and peroxynitrite. Although ROS are molecules that can exert huge damage, ROS also play an important role in various biological processes. Indeed, ROS can act as mediators and regulators of cell metabolism processes, ROS induce apoptosis, activate genes and are signaling molecules in various biological cascades. In addition, ROS are an essential part of the innate immune system.
Source of ROS
ROS originate from endogenous and exogenous sources. The main endogenous sources of ROS are the respiratory chain in the mitochondria and the immune system. Firstly, the respiratory chain in the mitochondria produces energy (ATP) by converting oxygen to water, a process that requires four electrons. However, in a few percent of the cases, electrons leak out of the respiratory chain, leading to an incomplete conversion of oxygen to water and the formation of ROS. The frequency and amount of electron leakage are higher when animals are kept for intensive farming. Secondly, ROS are a component of the killing response of immune cells to microbial invasion. During infections, ROS are generated by the immune cells in a mechanism called oxidative burst in which phagocytes use ROS to target and destroy foreign pathogens.
Exogenous sources of ROS also contribute to the total ROS load. These include amongst others: radiation, air pollution, chemicals, toxins and feed containing saturated fats and lipids. Other stress factors known to increase the level of ROS are heat stress, infection, weaning, intoxication (mycotoxins, heavy metals, …) and an unbalanced diet (e.g., high-fat diet). These stress factors are commonly seen in intensive farming.
As aerobic organisms are continuously exposed to large numbers of ROS, they have adapted to be able to defend themselves. Antioxidants are considered the defenders against ROS and are molecules that have the ability to scavenge and suppress the generation of ROS and to repair damaged DNA, proteins and oxidized lipids. Depending on their mode of action, antioxidants can be categorized as enzymatic antioxidants such as superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GSH-Px) and non-enzymatic antioxidants such as glutathione, vitamin C and E and several types of minerals (Cu, Mn, Zn, …).
When the production of or exposure to ROS exceeds the capacity of the antioxidant defense network, the animals experience oxidative stress. This imbalance leads to oxidative damage to cellular macromolecules such as lipids, proteins and DNA. Lipids in cellular membranes are easily oxidized leading to the loss of cell integrity. Protein oxidation results in malfunctioning enzymes and oxidation of DNA leads to breaks in DNA strands and mutations. Eventually, cells are functionally impaired with cell death (apoptosis or necrosis) and structural tissue damage as a result. In addition, ROS play an important role in the intracellular antioxidant and inﬂammatory pathways that lead to the production and release of antioxidants and pro-inﬂammatory cytokines, respectively. Depending on the concentration of ROS, one of both pathways will dominate. When the concentration of ROS is high, which is the case in oxidative stress, the antioxidants are not capable of neutralizing the large amount of ROS. Also, the inﬂammatory pathway dominates, leading to inﬂammation and the production of more ROS.
Oxidative stress influences animal performance significantly. The induced inflammation, together with the repair of damaged tissues requires energy and redirects nutrients away from production processes, resulting in economic losses for farmers.
References are available upon request.