SHOULD RADICALS BE FREE?
Free radicals have gained importance in the field of biology due to their central role in various physiological conditions as well as their implication in a diverse range of diseases. The free radicals or reactive oxygen species (ROS) are derived from both endogenous sources where the oxygen consumption is high (mitochondria, peroxisomes, endoplasmic reticulum, phagocytic cells etc.) and exogenous sources (mycotoxins, heavy metals, oxidized lipids).
A free radical can be defined as a molecule containing one or more unpaired electrons. The odd number of electron(s) of a free radical makes it unstable, short lived and highly reactive, hence the name of reactive oxygen species or ROS. Because of their high reactivity, they can exchange electrons with other compounds to attain stability. Thus, the attacked molecule gets its pool of electrons disturbed and becomes a free radical itself, beginning a chain reaction cascade which finally damages the living cell.
Reactive oxygen Species (ROS) are by-products of the oxygen metabolism. Most of the intracellular ROS are derived from the normal respiration process in mitochondria which is the main site of oxygen metabolism accounting for approximately 85-90% of the oxygen consumed by the cell.
But ROS are produced as well by phagocytic cells like neutrophils to aggress bacteria. Neutrophils accumulates ROS into their phagosomes and will release it either during phagocytosis of small bacteria or by secretion onto bacteria too large to be phagocyted.
Once released, the Reactive Oxygen Species will circulate and activate other neutrophils to attract them to the inflamed location. That contributes to activate the inflammation and the defense mechanisms against aggression.
Moreover, when inflammatory cells clean up damaged tissues, the destruction of the dead cells by the macrophages will lead to the production of even more ROS which can create a negative circle bringing about inflammation overheat.
Fortunately, physiology set up a control system of ROS to maintain homeostasis. The excess of ROS will trigger the synthesis of neutralizing enzymes. The most powerful neutralizing enzyme against ROS is the Superoxide Dismutase (SOD). The presence of SOD is essential to maintain the level of ROS under control, whether it is inside the mitochondria, inside cytosol or outside the cells.
Everything would work according to plan if there were no exogenous sources of ROS that could weaken the balance. In South East Asian highly productive farms, animals are exposed to four major exogenous causes of ROS; mycotoxins, oxidized lipids, heat, and/or heavy metals.
To fight against heat, the organisms will require the mitochondria to produce more energy leading to an increase supply of ROS that could overflow the pool of superoxide dismutase. That is part of what we call heat stress.
Mycotoxins at the opposite will negatively affect the production of Superoxide Dismutase and Catalase which will result as well in an increase of ROS.
All these exogenous causes will disturb the homeostatic balance between ROS and SOD and will lead to negative expression of ROS excess. ROS that were initially designed to help organisms to defend themselves against invaders are now becoming a threat for its host.
When in excess, free radicals like ROS can adversely affect various important classes of biological molecules such as nucleic acids, lipids, and proteins, consequently leading to tissue damage.
The mitochondrial DNA is more vulnerable to the ROS attack than the nuclear DNA, because it is located in close proximity to the ROS generated place. ROS, most importantly, the OH• radical directly reacts with all components of DNA such as purine and pyrimidine bases, deoxyribose sugar backbone and causes a number of alternations including single and double stranded breaks in DNA.
ROS can damage as well the RNA. The RNA is more prone to oxidative damage than DNA, due to its single stranded nature, lack of an active repair mechanism for oxidized RNA, less protection by proteins than DNA and moreover these cytoplasmic RNAs are located in close proximity to the mitochondria where loads of ROS are produced.
The lipid peroxidation is initiated, when any free radical attacks and abstracts hydrogen from a methylene group (CH2) in a fatty acid (LH) which results in the formation of a carbon centered lipid radical (L•). The lipid peroxidation results in the loss of membrane functioning, for example, decreased fluidity, inactivation of membrane bound enzymes and receptors. The lipid peroxidation is very important in vivo because of its involvement in various pathological conditions.
ROS oxidize different amino acids present in the proteins, causing formation of protein–protein cross linkages, results in the denaturing and loss of functioning of proteins, loss of enzyme activity, loss of function of receptors and transport proteins. The presence of carbonyl (C=O) groups in proteins has been considered as the marker of ROS mediated protein oxidation.
It can negatively affect the liver functions, induce damage in the intestinal tissue, compromise gut integrity in pigs and leads to an increase in inflammatory responses. Therefore, oxidative stress has been associated with impaired health status and reduced energy available for productive purposes. Studies evaluated at 30% the drop of performance under oxidative stress and inflammation explained by the excess of ROS and resulting catabolism.
SOD is therefore the main driving force in cell/body adaptation to various commercially relevant stress conditions as heat, mycotoxins or heavy metals. Since the superoxide radical is the main free radical produced in physiological conditions in the cell, SOD is believed to be the key element of the first level of cell defense against ROS. It is proven that additional synthesis of SOD under challenging conditions is an adaptive mechanism to decrease ROS formation and maintain adaptive homeostasis.
Nutritional means of SOD upregulation in swine and poultry production and physiological and commercial consequences of such upregulation has been subjected recently to many studies. For example, in the medical sciences, manipulation of SOD expression and SOD mimics are used as an important tool in disease prevention and treatment. Some new solutions are now available for nutritionists to reinforce Swine and Poultry defense mechanisms and that represent new strategies against mycotoxins and heat stress.