The Role Of Oxidative Stress On A Free Radicals

With all living organisms, a process known as cell respiration is integral in order to provide the body with an essential form of energy, adenosine triphosphate (ATP). Oxygen, although an essential part of this process, can form reactants from colliding with electrons associated with carrier molecules. (pb101.rcsb.org, 2017). Hydrogen peroxide is an integral product of this reaction but is known to impose negative effects on the body if high levels are introduced. Explicitly, this reaction is caused “If oxygen runs into (one of these) carrier molecules, the electron may be accidentally transferred to it. This converts oxygen into dangerous compounds such as superoxide radicals and hydrogen peroxide, which can attack the delicate sulphur atoms and metal ions in proteins.” (pdbh101.rcb.org, 2017). Research has suggested that the hydrogen peroxide can be converted into hydroxyl radicals, known to mutate DNA, which can potentially cause bodily harm due to DNA’s role in the synthesis of proteins. These radicals can cause detrimental effects on the human body, and studies have suggested a link to ageing. Due to the harmful effects of these H2o2, it is important that the body finds a way to dispose of hydrogen peroxide before concentrations are too great.

When we’re young, our cells have a very strong defense system known as superoxide dismutase (SOD) that kicks free radical butt. But as we get older, SOD doesn’t work as well. Without SOD keeping the peace, the free radicals have a field day and wreak as much damage as they possibly can causing our cells, and eventually us, to die. Free radicals have also been linked to a number of diseases such as cancer, dementia and heart disease.

Glutathione manages to act as a scavenger, neutralizing free radicals as they peruse the body. This counterbalance leads to the protection of our individual cells and thus our skin, eyes (lens, cornea, and retina), brain, heart, liver, kidneys, lungs, intestines as well as other tissues and organs from oxidative damages to ensure a better functioning,

In burns, free radicals and lipid peroxidation increases and also decreases the total antioxidant activity to deal with them and a reduction in antioxidant scavenging capacity. in the burn wound, increased inflammation and decreased tissue perfusion and increased activity of free radicals that makes it difficult healing process

Your body is in a constant battle against infection, diseases and the formation of free radicals. However, there's a secret weapon that can help you fight against these things: antioxidants! Antioxidants are elements such as vitamins A, C and E that counteract the damage caused by free radicals and help protect your healthy cells. Free radicals are the molecules that contain unpaired electrons, which make them highly reactive. In this form, they can cause damage by attacking healthy cells, and when these cells grow weakened, you become more vulnerable to disease.

Oxidation factors such as smoking cigarettes or bacterial infection can split apart molecules held by weak bonds, resulting in an unstable molecule with unpaired electron known as free radical.35 These free radicals start attacking the healthy nearby cells and attempt to replace their missing electron. When an attacked molecule loses its electron, it becomes a free radical itself. The damaged cell can release free radicals and continue the effects of oxidative stress to surrounding cells. The resulting oxidative stress can damage the endothelial cell wall by lipid peroxidation. Reactive oxidative species attack the cell membrane composed of polyunsaturated fatty acids by initiating the self-propagating chain reaction. Destruction of the cell membrane causes the osmotic disequilibrium that imbalances the entry/exit pathway of water molecules, proteins, enzymes, and other nutrients inside the cell. This further leads to cross-linking of proteins which disrupts extracellular signaling molecules to recognize their target proteins and utilize them for fulfilling specific functions in the body. Lipid peroxidation

Dr. Kosmider has publications with Dr. Steven Kelsen, who is a co-investigator on this grant. His clinical and research interests are focused on signaling pathways and the pathophysiology of oxidant stress-induced epithelial injury. He has training in respiratory medicine and physiology and will provide knowledge of the lung diseases. He has also collaborated with Dr. Muniswamy Madesh, a co-investigator in this project, who is an expert in studies of mitochondrial dysfunction and mechanisms of mitochondrial induced apoptosis.

Oxidative stress can be closely compared to “rusting” of mammal’s cells. Free radicals are unstable molecules that ravage or “oxidize” cells throughout the body in a process

Module ten discussed oxidative stress, and the causes, as well as consequences of liver disorders. Oxidative stress occurs when there is an abnormal balance between nonspecific oxidation reactions, and the body's ability to counteract them. A nonspecific oxidation reaction refers to one that involves free radicals reacting in a disorderly fashion with other molecules. Free radicals are highly reactive molecules that can cause cellular damage, targeting that of carbohydrates, lipids, proteins and nucleic acids. Free radicals within the body can lead to fragmentation of proteins causing them to have an abnormal function, oxidize polysaturated lipids at their double bond causing disruption in the membrane function, and cause mutations in DNA. Antioxidants react directly with free radicals in the body to render them inactive. Some antioxidant

Anti-oxidants are substances capable to mop up free radicals and prevent them from causing cell damage. Free radicals are responsible for causing a wide number of health problems which include cancer, aging, heart diseases, gastric problems etc. A free radical is an atom or molecule with a single unpaired electron. Examples: Nitric oxide (.NO), superoxide (O2.-) hydroxyl radical (.OH), lipid peroxy radical (LOO.). Although, molecular oxygen (O2) has two unpaired electrons in two different orbitals, it is not a free radical (23). After donating an electron, an antioxidant becomes a free radical by definition. In this state, antioxidants are not harmful because they have the ability to accommodate the change in electrons without becoming reactive

This free radical, which is initially formed as relatively unreactive, reacts very rapidly with oxygen to yield a highly reactive trichloromethyl peroxy radical (CCl3OO•). Both radicals are capable of binding to proteins or lipids, or abstracting a hydrogen atom from an unsaturated lipid, thus, initiating lipid peroxidation (Halliwell, and Gutteridge, 1990; Williams, and Burk, 1990; Lee, and Jeong, 2002). Lipid peroxidation may cause peroxidative tissue damage in inflammation, cancer, aging, ulcer, cirrhosis, and atherosclerosis. Therefore, inhibition of the cytochrome P450-dependent oxygenase activity could cause a reduction in the level of toxic reactive metabolites and a decrease in tissue injury. On the other hand, an elevation of plasma AST and ALT activities could be regarded as a sign of damage to the liver cell

Antioxidants are molecules capable of either delay or prevent the oxidation of other molecules. They terminate oxidative chain reactions by removing radical intermediates and inhibiting other oxidation reactions. Consequently, antioxidants are often reducing agents such as thiols or polyphenols (Hamid et al., 2010). The antioxidant defense systems are capable of blocking the initial production of free radicals, scavenging the oxidants and converting the oxidants to less toxic compounds. It also functions through blocking the secondary production of toxic metabolites, blocking the chain propagation of the secondary oxidants and repairing the molecular injury induced by free radicals (Kabel, 2014). The antioxidant defense system consists of powerful enzymatic and non-enzymatic antioxidants (Halliwell, 2007). The antioxidants are either endogenous or exogenous in origin (Fig. 8).

Free radicals cause oxidation of proteins, generally the amino acids; lysine, proline and arginine. Oxidative cleavage of the peptide backbone through the α-amidation pathway, oxidative cleavage of glutamyl and prolyl residues, emergence of protein-protein cross-linked derivatives, and cell membrane damage by lipid oxidation products give rise to reactive aldehydes and ketones known as protein

However, (H2O2) can react with reduced transition metals, via the Fenton reaction, to produce the highly hydroxyl radical (•OH), a far more damaging molecule to the cell. In addition to forming H2O2, O2•– radicals can rapidly react with nitric oxide (NO) to generate cytotoxic peroxynitrite anions (ONOO–) (Jeffrey et al., 2003). Peroxynitrite can react with carbon dioxide, leading to protein damage via the formation of nitrotyrosine and lipid oxidation. The generation of ROS in normal cells, including neurons, is under tight homeostatic control. To help detoxify ROS, enzymatic and non-enzymatic antioxidants including speroxide dismutase (SOD), glutathione, α-tocopherol (vitamin E), catalase, will react with most oxidants. In addition, the antioxidant enzymes catalase and glutathione peroxidase detoxify H2O2 by converting it to O2 and H2O. However, when ROS levels exceed the antioxidant capacity of a cell, a deleterious condition known as oxidative stress occurs. Unchecked, excessive ROS can lead to the destruction of cellular components including lipids, protein, and DNA, and ultimately cell death via apoptosis or necrosis (Birben et al., 2012; Jeffrey et al., 2003). Indeed the World Health organization (WHO) has initiated global initiatives on neurology and public health in an effort to increase public awareness of the prevalence, severity and cost of neurological disorders with a view to identify possibilities for prevention (WHO 2006). Current

Oxidative stress promotion: Disturbance of the prooxidant-antioxidant balance in favour of the former is termed as oxidative stress (Aly et al. 2010; Uchendu et al. 2012). The outcome of this multistep process is tissue damage which builds a path from the onset of tissue damage through diseases to finally apoptosis (Agrawal and Sharma 2010). Damage induced by oxidative stress occurs through the production of reactive oxygen species (ROS) which includes oxygen derived free radicals such as superoxide anion, hydroxyl radical and non radical derivatives as hydrogen peroxide (Tebourbi et al. 2011; Verma et al. 2007). ROS induces alterations and damage to macromolecules like lipids and proteins, most common phenomena being lipid peroxidation