In this post we'll discuss Free Radicals and how they may cause tissue injury as well as the mechanisms that the body uses to neutralise them.
Reperfusion Injury
A free radical is a chemical that is highly reactive due to the presence of an unpaired electron in its outer orbit. Free Radicals have a short half-life and are able to generate other free radicals in chain reactions which leads to extensive damage of the cell.
Free radicals are produced both endogenously and exogenously. Cellular metabolism results in the generation of reactive oxygen species (ROS), which is a type of free radical. Phagocytes also generate these and use them as part of the killing machinery. ROS are the most common free radicals. In addition to ROS, there are also reactive nitrogen species (RNS). Free radicals can also be generated exogenously by the action of ionizing radiation, drugs, pollutants and chemicals.
Tissues that are rich in polyunsaturated fatty acids are especially sensitive to the damaging effects of free radicals. The aim of a free radical is to try and steal an electron from another molecule in order to stabilise itself. Free radicals may react with proteins which may cause polymerisation, protein cleavage, and oxidation of –SH groups.
Free radicals may also damage nucleic acids which causes breaks, base modifications and mutations of the DNA. Cell membranes can also be damaged by free radicals due to lipid peroxidation of long-chain, mostly polyunsaturated fatty acids of the membrane. In this process, the free radicals initiate a chain reaction in which further free radicals are produced. The damage to the membrane affects the permeability of the membrane, secretion as well as ion transport.
However, the cells aren’t completely helpless and several intracellular and extracellular antioxidant mechanisms protect the cell from free radical injury. These include enzymes such as superoxide dismutase, catalase, and glutathione peroxidase which break down free radicals. Cells are rich in enzymatic antioxidants and the extracellular space has non-enzymatic or chemical antioxidants.
The lipid or water soluble chemical antioxidants sacrifice themselves when they come in contact with free radicals in order to save the cell. Vitamin E is an antioxidant which is embedded in the cell membrane and acts as a lipid soluble antioxidant and protects cell membranes. Vitamin C is also an antioxidant but is water soluble. Once a chemical antioxidant has donated an electron to a free radical (this neutralises the free radical), it gives off its own free radical. However, this free radical is less dangerous than the original. In addition, the antioxidants in the body work together as part of a network to protect the body from free radicals and one antioxidant is able to restore another.
Reperfusion is when blood supply is restored to a tissue after a period of time and further cell injury and death occurs as a result of this. During the period of ischaemia, an enzyme called xanthine peroxidase is generated. This enzyme generates free radicals when the blood supply is returned to the tissue. This is important in veterinary medicine, for example, when blood supply is returned to the large intestine of a horse after it has been repositioned to correct torsion. The injury caused by reperfusion can be reduced by administering drugs that inhibit xanthine peroxidase (e.g. allopurinol). Unfortunately, neutrophils may worsen the injury by producing free radicals when they try to kill micro-organisms.
That's what we need to know about free radicals for now, see you next time :)
