Normally, cells defend themselves against ROS damage with enzymes such as alpha-1-microglobulin, superoxide dismutases, catalases, lactoperoxidases, glutathione peroxidases and peroxiredoxins. Small molecule antioxidants such as ascorbic acid (vitamin C), tocopherol (vitamin E), uric acid, and glutathione also play important roles as cellular antioxidants. In a similar manner, polyphenol antioxidants assist in preventing ROS damage by scavenging free radicals. In contrast, the antioxidant ability of the extracellular space is less - e.g., the most important plasma antioxidant in humans is uric acid.
Effects of ROS on cell metabolism are well documented in a variety of species. These include not only roles in apoptosis (programmed cell death) but also positive effects such as the induction of host defencegenes and mobilisation of ion transport systems. This implicates them in control of cellular function. In particular, platelets involved in wound repair and blood homeostasis release ROS to recruit additional platelets to sites of injury. These also provide a link to the adaptive immune system via the recruitment of leukocytes.
Reactive oxygen species are implicated in cellular activity to a variety of inflammatory responses including cardiovascular disease. They may also be involved in hearing impairment via cochlear damage induced by elevated sound levels, in ototoxicity of drugs such as cisplatin, and in congenital deafness in both animals and humans. ROS are also implicated in mediation of apoptosis or programmed cell death and ischaemic injury. Specific examples include stroke and heart attack.
In general, harmful effects of reactive oxygen species on the cell are most often:
When a plant recognizes an attacking pathogen, one of the first induced reactions is to rapidly produce superoxide (O−
2) or hydrogen peroxide (H
2) to strengthen the cell wall. This prevents the spread of the pathogen to other parts of the plant, essentially forming a net around the pathogen to restrict movement and reproduction. In the mammalian host, ROS is induced as an antimicrobial defense. To highlight the importance of this defense, individuals with chronic granulomatous disease who have deficiencies in generating ROS, are highly susceptible to infection by a broad range of microbes including Salmonella enterica, Staphylococcus aureus, Serratia marcescens, and Aspergillus spp. The exact manner in which ROS defends the host from invading microbe is not fully understood. One of the more likely modes of defense is damage to microbial DNA. Studies using Salmonella demonstrated that DNA repair mechanisms were required to resist killing by ROS. More recently, a role for ROS in antiviral defense mechanisms has been demonstrated via Rig-like helicase-1 and mitochondiral antiviral signaling protein. Increased levels of ROS potentiate signaling through this mitochondia-associated antiviral receptor to activate interferon regulatory factor (IRF)-3, IRF-7, and nuclear facto- kappaB (NFκB), resulting in an antiviral state.