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Chapter 16 : Antioxidants and Brain Function in HIV/AIDS
Category: Viruses and Viral Pathogenesis
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Impaired neuroprotection, due to increased oxidative stress, has been implicated as a factor affecting neuronal degeneration in HIV/AIDS. This chapter reviews the role of biological antioxidants in maintaining adequate brain function in HIV-1 disease. Cognitive impairment is the major neurological complication of HIV-1 infection, ranging in severity from a mild subclinical cognitive deficit to a dementing illness (HIV-1- associated dementia [HAD]). The advent of protease inhibitors has raised the possibility of HIV-1 suppression and potential eradication, as well as potential neuropsychological benefit. Treatment with highly active antiretroviral therapy (HAART) appears to produce a beneficial effect on neurocognitive functioning. Microglial activation, through the mediation of oxidative stress, appears to play a major role in neuronal apoptosis and consequent neuronal loss in HIV-1-infected individuals. Antioxidants may also decrease neuropathogenesis through regulation of specific proinflammatory cytokines that contribute to neurodegenerative changes and are evident in HIV-1 disease. Alterations in nutritional status have long been acknowledged in various HIV-1-infected cohorts, including men who have sex with men, drug users, heterosexual adults, and children. Antioxidative treatment (daily intake of selenium, vitamin E, and vitamin C) has been reported to inhibit progression of mental deterioration in patients with multiple sclerosis. Moreover, antioxidant therapies have been reported to slow the progression of Alzheimer’s disease and improve cognitive function in late life for those without dementia.
Cytokines in HIV neuropathogenesis. Imbalanced cytokines (proinflammatory versus anti-inflammatory) in the brain tissue of HIV-infected individuals.
Potential action of selenium in reducing oxidative stress through its role in glutathione peroxidase activity, which protects the brain against lipoperoxidation. Cells are susceptible to the damaging actions of the small amounts of , OH, and H2O2 that inevitably form during metabolism, especially in the reduction of oxygen by the electron transfer system of mitochondria. Free reactive oxygen species react with lipids, particularly polyunsaturated fatty acids, initiating a process known as lipid peroxidation, and subsequent production of new reactive species. Both O2 and H2O2 need to be quickly removed from the system and, in general, are reduced by enzyme detoxification, involving catalase and selenium-dependent glutathione peroxidase (Se-GPx), the major protective enzyme against excessive oxidative stress in the brain.
Selenium and cytokine regulation. The rationale for a selenium-cytokine mechanism of action in neuroprotection has been demonstrated in studies indicating the potential for selenium to decrease neuropathogenesis through suppression of IL-induced HIV-1 replication and neuronal apoptosis ( Hori et al., 1997 ; Look et al., 1997 ; Moutet et al., 1998 ; Sappey et al., 1994 ).