Discussion The mechanism of arsenic-induced neurotoxicity is not well defined. Several metabolites of arsenic are able to pass through the blood-brain barrier and accumulate in the hippocampus and some other locations [13]. This affects the intracellular Ca(2+) homeostasis and ultrastructures of hippocampal neurons. In relation to the amino acid neurotransmission, report reveal that arsenic-induced excessive glutamate accumulation in the extracellular space induces excitotoxicity [29]. Arsenic exposure can alter epigenetic regulations and the signaling of hypothalamus-pituitary-adrenal axis (HPA). However, in the present study arsenic was not able to manifest any significant alteration in the DNA laddering pattern in cerebral cortex and cerebellum
…show more content…
Microscopy revealed a decreased number of pyramidal neurons in the superficial layers and presence of polymorphic cells in subgranular zone of ectal limb of dentate gyrus [30]. Astrocyte damage has been shown to be associated with myelin disintegration in the central nervous system. The modulation in the levels of myelin basic protein (MBP), myelin-associated glycoprotein and neurofilament (NF) are reported to be associated with arsenite toxicity. It also upregulate vacuolated axons, especially those are present in the corpus-callosum region [31]. Oxidative stress associated neurodegeneration have been reported as the result of arsenic toxicity [32]. This is evident in our present investigation. Since, cerebral and cerebellar DNA is found to be less interfered by arsenic so the arsenic-induced toxicities are mostly attributable at the cellular level in the current study. The decrease in cellular thiol content and increase in MDA in both neural tissues support this fact. The strong stimulation of GSH export from astrocytes by arsenate may contribute to the arsenic-induced neurotoxicity [32]. However, in our study we demonstrate the strong anti-oxidant capacity of green tea by thiol restoration/upregulation against arsenic toxicity in neuronal …show more content…
The uric acid, being an anti-oxidant has been regarded in delaying the senescence and ageing process [55]. The hypouricemic condition may facilitate diseases like multiple sclerosis [56]. The long term effects in the decrease in serum urate may sustain an increase in free radical product like MDA level, which may be linked to the neural-senescence promoting ability of arsenic [57]. The blocking of the molybdenum (Mo) center of xanthine oxidase by arsenic minimizes O2 reduction to form H2O2 during the formation of hypoxanthine to xanthine and xanthine to uric acid [58]. This incident results in the deleterious effects like decline in antioxidant capacity as a result of low urate level and decrease in rate of oxidation of more toxic arsenite (+3) to less toxic arsenate (+5) (Aposhian et al. 2003). Hydrogen peroxide is reduced to H2O by antioxidant enzymes like peroxidase and catalase [59]. In the present study, green tea has been decisively shown to restore the serum urate level with a concomitant decline in serum and tissue MDA level. The anti-ageing and life-span enhancing role of urate and SOD1 (cytosolic Cu-Zn SOD) are evident [55, 60]. In the current study, for the first time we demonstrate the role of green tea in promoting urate and SOD1 function in neural tissues to resist oxidative stress in arsenic-intoxicated
Microscopy revealed a decreased number of pyramidal neurons in the superficial layers and presence of polymorphic cells in subgranular zone of ectal limb of dentate gyrus [30]. Astrocyte damage has been shown to be associated with myelin disintegration in the central nervous system. The modulation in the levels of myelin basic protein (MBP), myelin-associated glycoprotein and neurofilament (NF) are reported to be associated with arsenite toxicity. It also upregulate vacuolated axons, especially those are present in the corpus-callosum region [31]. Oxidative stress associated neurodegeneration have been reported as the result of arsenic toxicity [32]. This is evident in our present investigation. Since, cerebral and cerebellar DNA is found to be less interfered by arsenic so the arsenic-induced toxicities are mostly attributable at the cellular level in the current study. The decrease in cellular thiol content and increase in MDA in both neural tissues support this fact. The strong stimulation of GSH export from astrocytes by arsenate may contribute to the arsenic-induced neurotoxicity [32]. However, in our study we demonstrate the strong anti-oxidant capacity of green tea by thiol restoration/upregulation against arsenic toxicity in neuronal …show more content…
The uric acid, being an anti-oxidant has been regarded in delaying the senescence and ageing process [55]. The hypouricemic condition may facilitate diseases like multiple sclerosis [56]. The long term effects in the decrease in serum urate may sustain an increase in free radical product like MDA level, which may be linked to the neural-senescence promoting ability of arsenic [57]. The blocking of the molybdenum (Mo) center of xanthine oxidase by arsenic minimizes O2 reduction to form H2O2 during the formation of hypoxanthine to xanthine and xanthine to uric acid [58]. This incident results in the deleterious effects like decline in antioxidant capacity as a result of low urate level and decrease in rate of oxidation of more toxic arsenite (+3) to less toxic arsenate (+5) (Aposhian et al. 2003). Hydrogen peroxide is reduced to H2O by antioxidant enzymes like peroxidase and catalase [59]. In the present study, green tea has been decisively shown to restore the serum urate level with a concomitant decline in serum and tissue MDA level. The anti-ageing and life-span enhancing role of urate and SOD1 (cytosolic Cu-Zn SOD) are evident [55, 60]. In the current study, for the first time we demonstrate the role of green tea in promoting urate and SOD1 function in neural tissues to resist oxidative stress in arsenic-intoxicated