There is without any doubt that ADR has been reported to give rise to the irreversible liver damage to trigger of the apoptotic processes in normal liver tissue. ADR-mediated hepatotoxicity has been shown to include focal damage in hepatocytes, vascular damage and steatosis. Thus, its hepatotoxicity was described subcellular hepatic alterations, including polymorphic mitochondria, cytoplasmic vacuolization and lipid droplet accumulation as well. Until now, the effect of compounds most of them antioxidant, such as vitamin E, erdosteine, cystathionine, ator (El-Moselhy and El-Sheikh 2014) and catechin on ADR-induced hepatotoxicity has been declared to prevention of liver injury induced by oxidative stress (Injac et al. 2008).
These proteins are initially in an inactive form, and are being activated when thrombin binds to thrombomodulin (Tazbir, 2004). Protein C are able to act as an anticoagulant which inhibit clotting factors Va and VIIIa when it work together with its cofactor protein S (Yamakawa et al, 2011). It is understood that inflammation is brought about by cytokine production in our body. In order to reduce inflammation, activated protein C is trigger. It also leads to an increased in fibrinolysis by inactivating plasminogen activator inhibitor-1 (PAI-1) (Tazbir, 2004).
Thrombin can stimulate inflammatory pathways, thus reducing fibrinolysis further. However, the activation is reduced in sepsis. One anticoagulant system that regulates thrombin formation is Protein C; which is converted to its activated form by thrombin. Thus, Activated Protein C (APC) alters the coagulation system, and in turn prevents thrombosis and promotes fibrinolysis (Esmon, 1989). Protein C is a naturally occurring anti-coagulant with key pathways that are beneficial in the treatment of sepsis; such as the cytoprotective mechanisms which include ant... ... middle of paper ... ...cts of recombinant human activated protein C in a ewe model of septic shock.
Myelin sheath degeneration might be resulted from the disease that directly damage the myelin sheath, or the disease that damage the oligodendrocytes (Love, 2006). Eventually, demyelination leads to the impairment of the normal conduction of the electrical impulses in the affected nerves. MULTIPLE SCLEROSIS Multiple sclerosis (MS) is the most common inflammatory demyelinating disease in the CNS. It is a chronic neurological disease that normally affects young people and it is one of the leading causes of disability. The pathological hallmark of this chronic disease is the formation of demyelinated plaques with the reactive glial scar tissue, which either focally or diffusely distributed throughout the brain and the spinal cord (Lucchinetti et al... ... middle of paper ... ...ns induced by effector CD8 T cells recognizing a sequestered antigen on oligodendrocytes.
Recent scientific evidence of pesticide-related brain disorders are reinforcing the dangers of pesticides, and providing researchers more insight into what treatment may be paramount for people who develop the disease from exposure to these chemicals. One of the most common brain disorders is Parkinson’s disease, which affects more than a million Americans. Recent investigations suggest that exposure to pesticides may increase the risk of this disease, especially those individuals with specific gene variants. Briefly, pesticides inhibit an enzyme called aldehyde dehydrogenase (ALDH). ALDH’s main function is to keep DOPAL, a natural toxin in the brain, regulated.
Glutaric aciduria type 1 (GA1) is a rare organic aciduria. It is caused by deficiency of glutaryl-CoA dehydrogenase; a key enzyme in the metabolism of lysine, hydroxylisine and tryptophan. Patients can suffer selective striatal degeneration that presents as motor delay, dystonia or acute motor regression during infancy. The symptoms are due to the accumulation of toxic metabolites and can be precipitated by periods of acute illness, infectious disease, immunizations and surgery. Management of GA1 relies on preemptive diagnosis followed by protein restriction, sustained carbohydrate intake during illness and promoting renal clearance of organic acids.
Genetically-altered, dopamine-producing tissues are currently being proposed as an alternative in transplant therapy of PD. As techniques become more refined, such "brain-grafting" may be the panacea for not only PD, but also for other debilitating diseases such as Huntington’s disease and Alzheimer’s disease. According to Fitzgerald (1992:215), the "cardinal pathological feature [of PD] is loss of neurons from the substantia nigra". Most of this loss occurs in the SNpc, of which approxima... ... middle of paper ... ...zgerald, M. J. T. Neuroanatomy: Basic and Clinical. London: Bailliere Tindall, 1992.
A major cell involved in the pathogenesis of MS, oligodendrocytes (OLs) are responsible for creating myelin (Zhang et al., 2009, p. 19162). MS patients present with reduced numbers of OLs, resulting in less production of myelin and impaired speed of neural transmission (Karussis, 2014, p. 134). In initial stages of the disease, remyelination occurs; however, as MS progresses, OLs become less able to repair the damage (Zhang et al., 2009, p. 19162). Notch1 and its ligand, Jagged1, have been identified as critical mediators of oligodendrocyte progenitor cell (OPC) recruitment and differentiation (Zhang et al., 2009, p. 19162). OPCs are recruited to demyelinated axons, where they differentiate into OLs, producing myelin to remyelinate CNS axons (Jurynczyk & Selmaj, 2010, p. 7).
It is a cofactor of α-ketoglutarate dehydrogenase and pyruvate dehydrogenase enzymes both within the citric acid cycle and transketolase enzyme in the pentose phosphate pathway. Severe B1 deficiency which may result from chronic alcoholism, diabetes or malnutrition is usually associated with Wernicke’s encephalopathy (WE). WE clinically characterised by confusion, ataxia, and nystagmus, is an acute neuropsychiatric disorder which arises as a result of inadequate supply of thiamine to the brain. Confusion and disorientation stem from the brain’s inability to oxidize glucose for energy because B1 is a crucial cofactor in glycolysis and the citric acid cycle. Deficiency leads to an increase in free oxygen radicals, cytokines, and alteration of the blood–b... ... middle of paper ... ...nt enzymes.
In normal physiological conditions, a balance is maintained between the ROS production and their detoxification by the appropriate antioxidants and phases 2 proteins. (Uttara, Singh, Zamboni & Mahajan, 2009). Oxidative stress can occur due too many pathological conditions, when the balance of prooxidants and antioxidants is disturbed oxidative damage could accumulate in proteins, lipids, carbohydrates and nucleic acids. In severe cases these events can lead to cell death. The process can directly alter the antioxidant systems by either inducing or inhibiting the proteins which take part in these systems.