Endotoxin depletes ascorbate in the guinea pig heart. Protecttve effects of vitamins C and E against oxidative stress

Rojas, C.; Cadenas, Susana; Herrero, A.; Méndez, Juan Manuel Álvarez; Barja, Gustavo

doi:10.1016/0024-3205(96)00346-3

Cited by 27 publications

(23 citation statements)

References 26 publications

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“…This study has demonstrated that patients with acute infection have markedly decreased plasma levels of total vitamin C, compared with normal controls, which agrees with previous fundamental or clinical studies [5,21,22]. Vitamin C and E are very important molecules involved in the first line defence in septic conditions, which generate high quantities of ROS.…”

Section: Discussionsupporting

confidence: 91%

Plasma antioxidant status in septic critically ill patients: a decrease over time

Doise

Aho²,

Quenot

et al. 2008

Fundamemntal Clinical Pharma

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Severe septic states in humans are responsible for intense intravascular oxidative stress, which induces numerous adaptive mechanisms. We determined time sequence changes in total plasma antioxidant capacity (TAC) and major plasma antioxidant concentrations, which have not been fully explained in septic conditions. A cohort of 56 consecutive septic patients (septic shock n = 37, severe sepsis n = 19) and six healthy volunteers. We compared TAC and antioxidant levels in patients with one of two degrees of septic states, at the onset of illness, to those of healthy volunteers. Thereafter, over a 10-day follow-up, we observed daily the time sequence changes of the two septic populations in terms of TAC and antioxidants. At the onset, there was no difference between the three groups in terms of TAC values (healthy subjects 2.18 +/- 0.04; severe sepsis 2.03 +/- 0.07; septic shock 2.09 +/- 0.09), then an equivalent time decline was observed in the two septic populations whatever the severity. TAC was statistically linked to uric acid, proteins in particular albumin and bilirubin (multivariate analysis), but no correlation was found with any vitamin (A, C and E). A sharp and persistent decrease in vitamin C concentrations was underlined. TAC, unaffected at first, deteriorated over time whatever the severity of the infection in these critically ill patients. TAC, unable to distinguish severe sepsis and septic shock, is unlikely to be a particularly useful outcome measure.

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Section: Discussionsupporting

confidence: 91%

Plasma antioxidant status in septic critically ill patients: a decrease over time

Doise

Aho²,

Quenot

et al. 2008

Fundamemntal Clinical Pharma

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“…Ascorbate also chemically reduces peroxynitrite and other reactive oxygen and nitrogen species (Kirsch and de Groot 2000). These scavenging actions may explain how ascorbate diminishes the levels of oxidizing free radicals in LPS‐exposed myocardium (Rojas et al . 1996) and neutrophils (Dwenger et al .…”

Section: Discussionmentioning

confidence: 99%

“…Additionally, cellular mechanisms of vitamin C transport and metabolism may be defective, as LPS depletes ascorbate from adrenal glands (Garcia et al . 1990), lung (Benito and Bosch 1997), and heart (Rojas et al . 1996).…”

Section: Discussionmentioning

confidence: 99%

Sepsis inhibits reduction of dehydroascorbic acid and accumulation of ascorbate in astroglial cultures: intracellular ascorbate depletion increases nitric oxide synthase induction and glutamate uptake inhibition

Korcok

Tyml³

et al. 2002

Journal of Neurochemistry

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Sepsis is associated with oxidative stress and impaired glutamatergic transmission in brain. We investigated whether sepsis impairs accumulation of the antioxidant, ascorbate, and uptake of glutamate by astrocytes. Bacterial endotoxin (Escherichia coli lipopolysaccharide, LPS) and the inflammatory cytokine, interferon-c (IFNc), were applied to primary astrocyte cultures to model sepsis. In the absence of ascorbate, the combination of LPS and IFNc (LPS + IFNc) up-regulated inducible nitric oxide synthase (iNOS) and decreased the initial rate of glutamate uptake by 50% within 24 h. Cell viability and facilitated glucose transport activity were not affected at 24 h. Pre-treatment with ascorbate-2-O-phosphate increased intracellular ascorbate concentration and attenuated the induction of iNOS and inhibition of glutamate uptake caused by LPS + IFNc. Subsequent experiments examined the mechanisms by which cells accumulate ascorbate. LPS + IFNc decreased slightly the initial rate of uptake of ascorbate and inhibited markedly the rate with which intracellular dehydroascorbic acid (DHAA) was reduced to ascorbate. We conclude that septic insult impairs astrocytic clearance of DHAA from the extracellular fluid and decreases intracellular ascorbate concentration. Furthermore, sepsis induces iNOS and inhibits glutamate uptake by astrocytes through mechanisms that can be modulated by intracellular ascorbate. These results indicate treatments that increase intracellular ascorbate concentration may be beneficial for patients at risk for neurologic complication in sepsis.

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“…In vitro studies showed that vitamin C inhibited the replication of bacteria and prevented H 2 O 2 injury to cultured microvascular endothelial cells [141]. In guinea pigs, which, like humans, cannot synthesize their own vitamin C, administration of endotoxin rapidly depleted vitamin C stores, preventing oxidative damage [142]. Circulating concentrations of vitamin C are markedly depleted in patients with sepsis [57,58,63].…”

Section: Antioxidant Protectionmentioning

confidence: 98%

Immune cells: free radicals and antioxidants in sepsis

Víctor

Rocha

Fuente

2004

International Immunopharmacology

278

191

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Endotoxin depletes ascorbate in the guinea pig heart. Protecttve effects of vitamins C and E against oxidative stress

Cited by 27 publications

References 26 publications

Plasma antioxidant status in septic critically ill patients: a decrease over time

Plasma antioxidant status in septic critically ill patients: a decrease over time

Sepsis inhibits reduction of dehydroascorbic acid and accumulation of ascorbate in astroglial cultures: intracellular ascorbate depletion increases nitric oxide synthase induction and glutamate uptake inhibition

Immune cells: free radicals and antioxidants in sepsis

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