Healthy rodents that are given chemotherapy show increase in cell death in the CNS, suppression of hippocampal neurogenesis, and decreases in levels of hippocampal catecholamines, as compared to baseline values.The etiology of chemotherapyinduced cognitive impairment is largely unknown, but several candidate mechanisms have been suggested, including oxidative stress, impaired bloodbrain barrier, neuroinflammation, and decreased neurogenesis, etc. Acute neurotoxicity due to FU is doserelated and generally selflimiting. Clinically relevant concentrations of FU are toxic for both CNS progenitor cells and nondividing oligodendrocytes in vitro and in vivo. Shortterm systemic administration of FU caused both acute CNS damage and a syndrome of progressively worsening delayed damage to myelinated tracts of the CNS associated with altered transcriptional regulation in oligodendrocytes and extensive myelin pathology. Functional analysis also provided the first demonstration of delayed effects of chemotherapy on the latency of impulse conduction in the auditory system, offering the possibility of noninvasive analysis of myelin damage associated with cancer treatment. Delayed neurotoxicity has been reported when Mofezolac fluorouracil was given in combination with levamisole; this form of subacute multifocal leukoencephalopathy is immunemediated. Although there is no report yet of FU increasing CNS oxidative stress, it has been shown to induce apoptosis in rat cardiocytes through intracellular oxidative stress, and to decrease glutathione in bone marrow cells. Another antimetabolite, MTX, can cross the bloodbrain barrier as well. An estimated to percent of cancer patients treated with chemotherapy experience CIPN. The peripheral nervous system consists of Mofezolac sensory neurons running from stimulus receptors that inform the CNS of the stimuli, and motor neurons running from the spinal cord to the effectors that take action.In CIPN, an anticancer drug could impair both sensory and motor functions.The symptoms usually start in the hands andor feet and creep up the arms and legs.CIPN can make it difficult to perform normal daytoday tasks like buttoning a shirt, sorting coins in a purse, or walking.The same pattern of oxidation was also revealed in the sciatic nerve and the spinal cord where the damage reached the DNA level. The anticancer drug cisplatin results in severe cell death of sensory neurons derived from dorsal root ganglia when apurinicapyrimidinic endonucleaseredox factor that is involved in DNA base excision repair of oxidative DNA damage and in redox regulation of a number of transcription factors is suppressed. These include vitamin C, vitamin E, glutathione, coenzyme Q, carotenoids, and melatonin, etc. For example, vitamin E supplementation in the AD mouse model demonstrated a reduction in A deposition and improved cognition. For treatment of ALS, many antioxidants have been developed in GA mice, including manganese porphyrin, rasagiline, DP and, MHLA, NAC and vitamin E. Mirtazapine, a lessknown antioxidant, has recently also shown chemoprotective effects against cisplatininduced oxidative stress and DNA damage in the rat brain. The antineuropathic effect of antioxidant silibinin or tocopherol reduces oxaliplatininduced behavioral alterations by about. Oxidative stress not only occurs through the overproduction of ROSRNS but also under a case of a depleted or weaken antioxidant system, for example the depletion of glutathione, in the cell.Blockage of a process with a reagent against ROS or RNS alone is not sufficient to confirm the involvement of ROS or RNS, since target specificity of the agent and complexity of signaling pathways in the cells all affect outcome of the assay.

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