Free radical biology & medicine
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Free Radic. Biol. Med. · Jan 1997
Randomized Controlled Trial Clinical TrialThe effects of intravenous antioxidants in patients with septic shock.
Oxidative stress is implicated in septic shock. We investigated the effect of intravenous antioxidant therapy on antioxidant status, lipid peroxidation, hemodynamics and nitrite in patients with septic shock. Thirty patients randomly received either antioxidants (n-acetylcysteine 150 mg/kg for 30 min then 20 mg/kg/h plus bolus doses of 1 g ascorbic acid and 400 mg alpha-tocopherol) or 5% dextrose. ⋯ Systemic vascular resistance index decreased at 120 min in the antioxidant treated patients (p = .003). The effect of antioxidants on hemodynamic variables has not previously been reported. Antioxidant administration may be a useful adjunct to conventional approaches in the management of septic shock.
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Free Radic. Biol. Med. · Jan 1997
ReviewNeuroprotection by the metabolic antioxidant alpha-lipoic acid.
Reactive oxygen species are thought to be involved in a number of types of acute and chronic pathologic conditions in the brain and neural tissue. The metabolic antioxidant alpha-lipoate (thioctic acid, 1, 2-dithiolane-3-pentanoic acid; 1, 2-dithiolane-3 valeric acid; and 6, 8-dithiooctanoic acid) is a low molecular weight substance that is absorbed from the diet and crosses the blood-brain barrier. alpha-Lipoate is taken up and reduced in cells and tissues to dihydrolipoate, which is also exported to the extracellular medium; hence, protection is afforded to both intracellular and extracellular environments. Both alpha-lipoate and especially dihydrolipoate have been shown to be potent antioxidants, to regenerate through redox cycling other antioxidants like vitamin C and vitamin E, and to raise intracellular glutathione levels. ⋯ We propose that the various metabolic antioxidant properties of alpha-lipoate relate to its possible therapeutic roles in a variety of brain and neuronal tissue pathologies: thiols are central to antioxidant defense in brain and other tissues. The most important thiol antioxidant, glutathione, cannot be directly administered, whereas alpha-lipoic acid can. In vitro, animal, and preliminary human studies indicate that alpha-lipoate may be effective in numerous neurodegenerative disorders.
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Free Radic. Biol. Med. · Jan 1997
Clinical evidence of peroxynitrite formation in chronic renal failure patients with septic shock.
The production of both nitric oxide (NO) and superoxide increases in septic shock. The cogeneration of these molecules is known to yield peroxynitrite, which preferentially nitrates tyrosine residues of protein and non-protein origins. We present evidence of peroxynitrite production in septic shock by measuring plasma nitrotyrosine. ⋯ Plasma nitrotyrosine levels were not detectable in volunteers, 28.0 +/- 12.3 microM (1.6 +/- 1.1% of total tyrosine) in renal failure patients without septic shock, and 118.2 +/- 22.0 microM (5.5 +/- 1.2% of total tyrosine) in patients with septic shock. NOx levels were also higher in patients with septic shock than in patients without septic shock (173.9 +/- 104.7 vs. 75.6 +/- 19.1 microM). Although renal failure itself increases plasma concentrations of both molecules, the higher levels in patients with septic shock suggest that peroxynitrite is generated and the nitration of tyrosine residues is increased in this disease.