Oxidative Stress

The AAP is a potential trigger of cytochrome P450 that induced the high reactive quinone-imine production. This matches with sulphahydryl groups in proteins and result in rapid depletion to intracellular glutathione(35). Generally, one parts of the potential intracellular antioxidant defensive system is glutathione that consumes the singlet oxygen, superoxide and hydroxyl radicals(36). Enhancing of intracellular flux of oxygen free radicals results from glutathione depletion leads to oxidative stress in hepatocytes(36). The increasing the serum levels of GOT, GPT and ALP have been attributed to the structural integrity hepatic damage(37). In liver tissue, GOT and GPT are located in cytosol and mitochondria. In following of liver damage, hepatocyte transport function disturbed

Studies have shown that hydroxyl radical is responsible for oxidative DNA damage. Hydroxyl radicals come from the reaction between ascorbate (vitamin C), uranyl acetate, and hydrogen peroxide as illustrated in scheme 1 . The mechanism of DNA damage begins when the reaction between uranyl acetate and ascorbate (vitamin C) makes plasmid relaxation in pBluescript DNA. pBluescript DNA is a phagemid which includes many advantageous sequences for utilizing cloning with bacteriophage. The rate of DNA strand breaks multiply when the reaction between ascorbate (vitamin C), and uranyl acetate increase. In addition, hydrogen peroxide is the end product when there is a reaction between uranyl ion and ascorbate. DNA damage can happen

Liver is a complex organ which has vital functions in synthesis , detoxification and regulation; its failure therefore has life threatening condition.

Based from observations made in the early 1950s, Denham Harman proposed that functional decline in cells and tissues was due to cumulative effects of macromolecular damage caused by oxygen radicals produced by respiratory enzymes (Harman 1956). This theory proposes that superoxide and other free radicals cause damage to the macromolecular components of the cell, resulting in accumulated damage to cause cells, and eventually organs, to stop functioning, leading to the aging phenotype (Sohal and Weindruch 1996, Clancy and Birdsall 2013). Oxidative damage is thought to occur from an imbalance when the antioxidant systems are unable to counter all the free radicals continuously generated during the life of the cell.

Excessively high levels of free radicals cause damage to vital cellular components such as proteins, membrane lipids, and nucleic acids, and finally lead to cell death (Maritim, Sanders & Watkins 2003).

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

Metabolism and genetics also participate in cirrhosis for example abnormal collection of iron (hemochromatosis) or copper (Wilson's disease) in the liver causing injury, scarring and cirrhosis. Further cause of cirrhosis is the Autoimmune chronic active hepatitis that happens when the immune system attacks the liver and causes inflammation, damage, and cirrhosis. Drugs and chemicals also cause injury of the liver.

Chronic liver failure from an inability for the organ to repair itself from repeated injury and scarring that remains permanent. Alcoholic liver disease is the 2nd most common diagnoses for liver transplant, however many candidates must abstain from alcohol for a required period in addition to adhering to an abuse program. Metabolic liver disease is a non- alcoholic steatohepatitis where inflammation and scarring can occur from a development of fatty liver not related to alcohol but rather obesity or disorders such as diabetes and hyperlipidemia. Autoimmune liver disease or (AIH) autoimmune hepatitis where the patient’s own immune needs to be suppressed to prevent destruction of the liver (Tan, 730). Vascular liver disease results in poor blood flow or clotting of hepatic veins and hepatocellular carcinoma (HCC) in which liver transplantation will unquestionably cure HCC so long that the cancer does not spread beyond the liver (Bryce,

Cirrhosis refers to a combination of liver diseases that interfere with the normal function of the liver after destroying liver structures. The disease causes the formation of scar tissue in the liver that kills liver cells thereby causing inflammation (Fabris 716). The cells that have survived would tend to multiply rapidly to replace the dead cells. It results to regenerative nodules in the scar due to clustering of the newly formed liver cells. Cirrhosis is caused in varied ways that range from the chemical cause like alcohol to viruses. Besides, heavy and toxic metals like mercury, lead, copper and iron cause cirrhosis if they accumulate in the liver. The liver is a detoxicating organ of the body that purify

Glutathione helps to protect cells from reactive oxygen species. GSH checks free radical damage and helps detoxification by conjugating with chemicals. Increase in reactive oxygen species protection causes GSH depletion. GSH acts as cofactor for Glutathione Peroxidase (GPx) and Glutathione-S-transferase (GST). Glutathione-S-transferase is thought to play a physiological role in initiating the detoxification and these enzymes catalyse the reaction of such compounds with the -SH group of glutathione, thereby neutralizing their electrophilic sites and rendering the products more water-soluble. GPx is present throughout the tissues as four different isoenzymes, cellular, extracellular glutathione peroxidase, as phospholipid hydroperoxide glutathione peroxidase and gastrointestinal glutathione peroxidase (Alam et al 2013). GPx low activity is one of the early consequences of a disturbance of the prooxidant or antioxidant balance due to toxic exposure. Glutathione reductase plays an important role in maintaining a basic GSH pool, via catalysing the reduction of glutathione disulfide (GSSG) to GSH in NADPH-dependent reaction (Yao Chen et al

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

Antioxidants are molecules that find and destroy the free radicals floating in the bloodstream man. Free radicals are the main culprit for man is aging rapidly, destroying brain cells.

Liver disease resulting from alcohol affects more than two million Americans and is one of the primary causes of illness and death. The liver frees the body of harmful substances, such as alcohol. While the liver breaks down alcohol, it produces toxins that can be even more dangerous than the alcohol consumed (“Beyond Hangovers: Understanding Alcohol's Impact Your Health” 13). “These by-products damage liver cells, promote inflammation, and weaken the body’s natural defenses. Eventually, these problems can disrupt the body’s metabolism and impair the function of other organs” (“Beyond Hangovers: Understanding Alcohol's Impact Your Health” 13). A condition called steatosis is the result of fat build up in the liver and is the

Peroxynitrite can either oxidize or nitrate different biological molecules like thiols, tyrosine residues in proteins and phospholipids having unsaturated fatty acids. Radicals derived through peroxynitrite carries out one-electron reactions, form sulphilic and sulphonic acid derivatives (Quijano et al., 1997; Bonini and Augusto, 2001). Purine bases, present in DNA, are susceptible to oxidation and adduct

After internalization of C. albicans in phagocytes, it has been observed that the target fungal pathogen like any other microbial pathogen follows the path from phagosomes to phagolysosomes and gets fumigated and killed. During infection, Candida species are exposed to higher levels of reactive oxygen species (ROS), reactive nitrogen species (RNS) and antimicrobial peptides, low pH and reactive chloride species (HOCl) inside macrophages and neutrophils, and survival through these harsh conditions is essential for establishing disease and virulence. C. albicans evolved systems to directly scavenge the ROS produced by host cells and establish systemic infection. C.