Oxidative stress in HIV demented patients and protection ex vivo with novel antioxidants

J. Turchan, C. B. Pocernich, C. Gairola, A. Chauhan, G. Schifitto, D. A. Butterfield, S. Buch, O. Narayan, A. Sinai, J. Geiger, J. R. Berger, H. Elford, A. Nath

Research output: Contribution to journalArticle

Abstract

Objective: To determine the role of oxidative stress in mediating HIV dementia and to identify novel therapeutic compounds that may block this oxidative stress. Methods: Brain tissue from patients with HIV encephalitis and macaques with simian immune deficiency virus encephalitis was immunostained for lipid peroxidation. Oxidized proteins in CSF of patients with various stages of HIV dementia were quantitated and we determined whether CSF from these patients could alter mitochondrial function. Several novel compounds with antioxidant effects were screened to determine their relative efficacy in protecting against CSF-induced neurotoxicity. Results: Evidence for oxidative stress was present both in brain and in CSF. The presence of oxidized proteins in the CSF and CSF-induced progressive decrease in mitochondrial activity correlated with the severity of cognitive impairment, but only the group of patients with moderate to severe dementia reached statistical significance. L-deprenyl, didox, imidate, diosgenin, and ebselen blocked the CSFinduced toxicity. No effect of trimidox, ruthenium red, or Quercetin was seen. Conclusions: Increased oxidative stress is present in brain and CSF of HIV-infected patients. There is also an accumulation of toxic substances in the CSF that are capable of inducing oxidative stress. The authors have identified several novel compounds that are capable of blocking the CSF-induced toxicity, the therapeutic potential of which is worthy of further exploration.

Original languageEnglish (US)
Pages (from-to)307-314
Number of pages8
JournalNeurology
Volume60
Issue number2
StatePublished - Jan 28 2003

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Oxidative Stress
Antioxidants
HIV
AIDS Dementia Complex
3,4-dihydroxybenzohydroxamic acid
Brain
Imidoesters
Diosgenin
Encephalitis Viruses
Selegiline
Ruthenium Red
Poisons
Quercetin
Macaca
Encephalitis
Lipid Peroxidation
Dementia
Proteins
Therapeutics

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Turchan, J., Pocernich, C. B., Gairola, C., Chauhan, A., Schifitto, G., Butterfield, D. A., ... Nath, A. (2003). Oxidative stress in HIV demented patients and protection ex vivo with novel antioxidants. Neurology, 60(2), 307-314.

Oxidative stress in HIV demented patients and protection ex vivo with novel antioxidants. / Turchan, J.; Pocernich, C. B.; Gairola, C.; Chauhan, A.; Schifitto, G.; Butterfield, D. A.; Buch, S.; Narayan, O.; Sinai, A.; Geiger, J.; Berger, J. R.; Elford, H.; Nath, A.

In: Neurology, Vol. 60, No. 2, 28.01.2003, p. 307-314.

Research output: Contribution to journalArticle

Turchan, J, Pocernich, CB, Gairola, C, Chauhan, A, Schifitto, G, Butterfield, DA, Buch, S, Narayan, O, Sinai, A, Geiger, J, Berger, JR, Elford, H & Nath, A 2003, 'Oxidative stress in HIV demented patients and protection ex vivo with novel antioxidants', Neurology, vol. 60, no. 2, pp. 307-314.
Turchan J, Pocernich CB, Gairola C, Chauhan A, Schifitto G, Butterfield DA et al. Oxidative stress in HIV demented patients and protection ex vivo with novel antioxidants. Neurology. 2003 Jan 28;60(2):307-314.
Turchan, J. ; Pocernich, C. B. ; Gairola, C. ; Chauhan, A. ; Schifitto, G. ; Butterfield, D. A. ; Buch, S. ; Narayan, O. ; Sinai, A. ; Geiger, J. ; Berger, J. R. ; Elford, H. ; Nath, A. / Oxidative stress in HIV demented patients and protection ex vivo with novel antioxidants. In: Neurology. 2003 ; Vol. 60, No. 2. pp. 307-314.
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