Phase 2 Detoxification Research Paper

enable the substrate to bind to the enzyme and form the enzyme substrate complex and

Xenobiotic metabolism is usually divided to phase I and II, where polar function groups are unmasked or introduced to the chemical structure (phase I or activation), followed by the conjugation between the xenobiotic and endogenous molecules, notably glucuronic acid, to further improve hydrophilicity (phase II or conjugation) (Golan 2012). Hepatic microsomal P450 are the enzymes that dominate the catalysis of phase I metabolism of xenobiotics (Table 1 and 2) (Anzenbacher and Anzenbacherova 2001). Therefore,

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

Superoxide dismutase has a job of repairing the damage to the cells that the reactive oxygen species causes. When glutathione decreases in the body, it leads to the increase of reactive oxygen species and damages the DNA in the body. Also, glutathione (GSH) and superoxide dismutase (SOD) help the brain to clean and remove the toxicity bypass easily into the brain tissues. Glutathione combines to toxic metals from the brain and tissues, and then removes it by a pathway through the bile to the feces, and out of the body. When the amount of glutathione falls, because of exposure to toxic metals, it leads to loads of toxicity in the kidney. Then, because these toxic metals are very large and destroy the renal tubule cells, it leads to less excretion and an acid shift of the blood. When glutathione fails to remove the toxicity of metals from the body, it causes more damage to the kidney, and the increase of toxicity will increase reactive oxygen species levels. Then, this leads to the risk of cancer and immune linked illnesses. Porphyria in the urine can show us that the kidneys have failed to work. In addition, because glutathione has a function that works as an antioxidant and neutralizes free radicals, this helps

(Morini, et al.,1991). These peripheral transformations could even generate local levels of some derivatives that exceed the circulating levels of THs (Saba,et al.,2010).

The purpose of this paper is to compare and contrast how a toxin will affect the systems in the

it is also known as redox signalling. oxidative stress is due to metabolism mechanism caused due to oxidation this further causes damage to the bases its pairs present in the dna as well as breaks the dna strand at some parts which causes mutation as a result. the oxidative stress effects can be indirect direct. they are mostly indirect later causes harmful changes to the body by harming the physiological as well as psychological processes. the indirect effects are caused due to the generation or production of reactive oxygen species reactive nitrogen species. the ros produced includes o2- superoxide radical oh- hydroxyl radical h2o2 hydrogen peroxide some of these ros acts like intra cellular transport messengers in redox signalling. the ros also causes interference in standard cellular messaging mechanism. oxidative stress drives through discrete reversible site specific modifications/alterations of certain proteins. the redox signalling initiates the changes performed by reactive oxygen species reactive nitrogen species. they aim certain proteins its activities which are under certain networks or channels occurring in the

The liver’s complex biochemical process of detoxification is a two phase process, converting the byproducts of metabolism and toxins to render them into safer substance. Phase one, an enzymatic process, involves approximately 100 enzymes in the cytochrome P450 system. In Phase one, the chemical reaction known as biotransformation changes the toxin in to a less toxic, water-soluble substance to allow it to be safely excreted through the kidneys or colon. Enzymes do this through oxidation, the loss of electrons, or reduction, the gain of elections. Most of the time, the enzymatic reactions in Phase one decrease the toxicity of the substance, however, a more toxic intermediate substance may be produced, this is known as bioactivation.

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

target site while avoiding healthy normal tissue toxicity Vedam et al. (2003); Kini et al.

This then reaches the liver which sees them as toxin and waste energy. It tries to tackle them, but it allows other toxins to build up.

Nelsen et al. (2014) presents and discusses what the authors believe to be the inconsistencies among the definitions of poisons, venoms, and toxins, as well as the conflation, or mixing, of these terms within the literature. The three primary classes of toxins, biological, anthropogenic, and environmental, are defined and distinguished so that the authors can further discern the biological toxins using their own classification scheme (Nelsen et al. 2014). Nelsen et al. (2014) presents the necessity of their three-class scheme, which they proposed due to the terminological inconsistencies within and among the literature on biological toxins. I think implementing a new term to detract from the misconstruction of existing toxicological definitions would be constructive, especially with the proposed corresponding binomial classification system. This review aims to discuss the breadth and functionality of the Nelsen et al. (2014) categorization of toxins.

The major harmful effects of free radicals include oxidative stress and nitrosative death. Oxidative death is caused by ROS and nitrosative death by RNS. When the cells are unable to maintain the state of ‘Redox Homeostasis’ (keeping equilibrium between the beneficial and harmful effects of free radicals) it causes oxidative stress through the generation of ROS (12) and resultant oxidative injury. Potential biological damage happens when there is an overproduction of ROS and RNS and a down regulation of enzymatic and non-enzymatic antioxidants. Since ROS owns impact of powerful oxidizing agents, they interfere with the expression of a number of genes involved in the activation of signal transduction cascades (13, 14), apoptosis (15,16) etc.

A/the central regulator of GSH homeostasis, hence redox balance mitigation of neuron apoptotic death [5], is the master transcription factor, nuclear factor E2-related factor 2 (Nrf2). Nrf2 regulated genes include glutamate-cysteine ligase (GCL) (rate limiting enzyme in GSH synthesis), glutathione reductase (generation of reduced/active GSH), and multiple components of the gamma glutamyl cycle by which the GSH synthesis substrate, Cys is supplied to neurons in addition to dietary source(s) [20, 25]. Previous study in our laboratory addressed Nrf2/ARE (Antioxidant Response Element)-mediated neuroprotection which should prevent neuron death by maintaining GSH homeostasis [7]. E does up-regulate Nrf2 and the knockout of Nrf2 illustrated that this increase in Nrf2 confers a certain degree of neuroprotection [7]. However, somehow E prevents Nrf2 from providing complete protection and a population of fetal neurons still succumbs unless we artificially increase Nrf2 beyond its innate capacity [7].

antioxidant enzymes including small-molecule-weight antioxidants depends on cellular redox environment as it is a delicate process to regulate the two. ROS are responsible to regulate several physiological actions such as the ability to mediate and relate signal transduction from membrane receptors, At low concentrations, ROS are involved in regulating several physiological actions, including their ability to mediate relate signal transduction from membrane receptors, thus aiding the stimulation of several proteins and enzymes (1,2). Conversely, accumulation of extra intracellular ROS lead to oxidative stress, in turn will impair cellular membranes, promoting mitochondrial injury and cell death, which adversely impacting upon cell function and survival 3,5)