Interactions of peroxynitrite with human plasma and its constituents: oxidative damage and antioxidant depletion

Endothelial cells and activated phagocytes produce both nitric oxide (.NO) and superoxide (O2.-), which react to form peroxynitrite. Peroxynitrite has been suggested to be directly cytotoxic and also to decompose into other toxic species. In order to understand the consequences of peroxynitrite generation in vivo, we examined its reaction with human blood plasma. Peroxynitrite decreased the total peroxyl-trapping capacity of plasma. In terms of specific antioxidants, addition of peroxynitrite to plasma leads to rapid oxidation of ascorbic acid, uric acid and plasma SH groups. The oxidation of plasma SH groups was enhanced in dialysed plasma and returned to control levels by the addition of physiological levels of bicarbonate. Evidence was found for formation of nitro-adducts to aromatic side chains in plasma proteins by peroxynitrite. Peroxynitrite also leads to depletion of ubiquinol and formation of traces of lipid hydroperoxides in plasma, although alpha-tocopherol levels were only slightly decreased. Peroxynitrite formation in human body fluids is likely to cause antioxidant depletion and oxidative damage.

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Protection of vitamin E, selenium, trolox C, ascorbic acid palmitate, acetylcysteine, coenzyme Q0, coenzyme Q10, beta-carotene, canthaxanthin, and (+)-catechin against oxidative damage to rat blood and tissues in vivo

Free Radical Biology and Medicine ◽

10.1016/0891-5849(94)00238-f ◽

1995 ◽

Vol 18 (5) ◽

pp. 949-953 ◽

Cited By ~ 58

Author(s):

Hao Chen ◽

Al L. Tappel

Keyword(s):

Ascorbic Acid ◽

Vitamin E ◽

Oxidative Damage ◽

Coenzyme Q10 ◽

Beta Carotene ◽

Rat Blood ◽

Coenzyme Q0 ◽

Trolox C

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Plasma Protein Oxidation and Antioxidant Defense During Aging

International Journal for Vitamin and Nutrition Research ◽

10.1024/0300-9831.71.6.332 ◽

2001 ◽

Vol 71 (6) ◽

pp. 332-338 ◽

Cited By ~ 10

Author(s):

Silvano Garibaldi ◽

Sabina Valentini ◽

Irene Aragno ◽

Maria Adelaide Pronzato ◽

Nicola Traverso ◽

...

Keyword(s):

Oxidative Damage ◽

Plasma Protein ◽

Plasma Proteins ◽

Antioxidant Defense ◽

Protein Carbonyl ◽

Carbonyl Groups ◽

High Turnover ◽

Older Subjects ◽

Molecular Damage

Background: Oxidative stress is an important process that occurs in vivo during aging and is considered one of the main causes of molecular damage to cellular and tissue structures. These changes can accumulate in biological structures during aging. Objective: The aim of this work is to evaluate plasma protein oxidative damage, measured as carbonyl groups content, and the concentration of some antioxidant molecules (vitamins and carotenoids) in 122 healthy volunteers (50 males and 72 females), 25 to 89 years old. Results: Total plasma proteins slightly decreased with age, but the level of carbonyl groups was similar in the adult (< 65 years) and in the old, and was similar in both sexes. Plasma concentration of antioxidant molecules such as a-tocopherol, b-carotene and other carotenoids, increased with age and correlated with the level of lipoproteins; plasma total cholesterol and triglycerides were significantly correlated with age as well. Conclusions: The surprisingly normal level of plasma protein carbonyl groups in our older subjects suggests two possibilities: a) the older people in our study are healthy and free from pathologies because of better protection against oxidative injury during their lifetimes, i.e., they maintained low-level oxidative damage on plasma proteins; or b) the level of carbonyl groups is normal because of the high turnover in plasma: the oxidized circulating proteins are preferentially and quickly removed; in this case oxidative damage is not discernible in plasma proteins but may proceed silently in other tissues.

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Real-time profiling of kidney tubular fluid nitric oxide concentrations in vivo

AJP Renal Physiology ◽

10.1152/ajprenal.2001.281.1.f189 ◽

2001 ◽

Vol 281 (1) ◽

pp. F189-F194 ◽

Cited By ~ 31

Author(s):

David Z. Levine ◽

Michelle Iacovitti ◽

Kevin D. Burns ◽

Xueji Zhang ◽

Keyword(s):

Nitric Oxide ◽

Ascorbic Acid ◽

Proximal Tubule ◽

Real Time ◽

Zero Point ◽

Renal Ablation ◽

Highly Sensitive ◽

Early Proximal Tubule

To directly determine intratubular nitric oxide concentrations ([NO]) in vivo, we modified amperometric integrated electrodes (WPI P/N ISO-NOP007), which are highly sensitive to NO and not affected by ascorbic acid, nitrite, l-arginine, or dopamine. Although reactive lengths were as short as 5 μm long, the electrode still responded rapidly. With the use of kidney surface fluid as the “zero point,” the electrode tip was inserted into tubular segments along the track of a perforation made by a beveled glass pipette. The surface fluid zero point was usually stable as distal, late proximal, and early proximal tubule [NO] levels were measured sequentially in the same nephron. In eight normal rats, distal, late proximal, and early proximal [NO] concentrations were each ∼110 nM. In contrast, in nine 5/6 nephrectomized rats 2 wk postsurgery, although [NO] also did not differ among distal, late proximal, and early proximal segments, levels were approximately fourfold higher than those in normal rats and were significantly reduced after N G-monomethyl-l-arginine administration. These are the first quantitative in vivo tubular fluid [NO] measurements and show a significant increase in tubular fluid [NO] after renal ablation.

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The effect of iron overload on rat plasma and liver oxidant status in vivo

Biochemical Journal ◽

10.1042/bj3000799 ◽

1994 ◽

Vol 300 (3) ◽

pp. 799-803 ◽

Cited By ~ 107

Author(s):

A J Dabbagh ◽

T Mannion ◽

S M Lynch ◽

B Frei

Keyword(s):

Oxidative Stress ◽

Lipid Peroxidation ◽

Ascorbic Acid ◽

Iron Overload ◽

Alpha Tocopherol ◽

Plasma Ascorbic Acid ◽

Ample Evidence ◽

Endogenous Antioxidants ◽

Oxidant Status

There is ample evidence implicating reactive oxygen species in a number of human degenerative diseases such as atherosclerosis and haemochromatosis. Although lipid peroxidation underlies many of the toxic effects of oxidative stress, there is a lack of a sensitive and reliable method for its assessment in vivo. To understand the implications of oxidative stress in vivo, we have used dietary iron overload (IO) in the rat. Oxidant status in these animals was determined by assessing depletion of endogenous antioxidants and formation of various lipid peroxidation products, including acylated F2-isoprostanes, a novel class of free-radical-derived prostaglandin-F2-like compounds. IO led to a significant decrease in the concentration of the antioxidants alpha-tocopherol and ascorbic acid in plasma, and alpha-tocopherol, beta-carotene and ubiquinol-10 in liver. Whereas there was no significant lipid peroxidation in plasma, hepatic F2-isoprostane levels were moderately but significantly increased in IO. In addition, IO caused a significant increase in plasma total and high-density lipoprotein cholesterol levels, an effect that was correlated with depletion of plasma ascorbic acid but not alpha-tocopherol. The data demonstrate that IO causes lipid metabolism disturbances and oxidative stress which is associated with substantial depletion of endogenous antioxidants and moderate lipid peroxidative damage.

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Synergistic Hepatoprotective Interaction between α-Tocopherol and Ascorbic Acid on Paracetamol Induced Liver Damage in Rats

10.20944/preprints202006.0122.v1 ◽

2020 ◽

Cited By ~ 1

Author(s):

Saidul Islam Khan ◽

Mahmuda Begum ◽

Rama Chowdhury ◽

Md. Mizanur Rahman ◽

Muhammad Asaduzzaman

Keyword(s):

Ascorbic Acid ◽

Vitamin E ◽

Liver Damage ◽

Treated Group ◽

Alpha Tocopherol ◽

Male Rats ◽

Control Group ◽

Group I ◽

Control Group Group

Background and objectives: The hepatoprotective activity of vitamin E and C is evident due to their ability of modulating the antioxidant pathway. In this study, we have evaluated the effects of α-tocopherol and ascorbic acid on paracetamol induced liver damage with offsetting various levels of drug treatment following an in vivo experimental protocol on Wistar albino male rats. Materials and Methods: The level of lipid peroxidation as well as histological examination of liver tissues were observed among 50 Wistar albino male rats to evaluate hepatoprotective effect of α-tocopherol and ascorbic acid on hepatocytes. The experiment was divided into 5 groups (10 rats in each group)- Basal control group (Group-I, with propylene glycol), Paracetamol treated control group (Group –II), α-tocopherol pretreated & paracetamol treated group (Group –III), Ascorbic acid pretreated & paracetamol treated group (Group –IV) and Ascorbic acid pretreated & paracetamol treated group (Group –IV). Results: The mean (± SD) Malondialdehyde (MDA) concentration were significantly reduced in α-tocopherol pretreated and paracetamol treated group (P<0.001), Ascorbic acid pretreated and paracetamol treated group (P≤0.05) and combined α-tocopherol with ascorbic acid pretreated & paracetamol treated group (P<0.001). Statistically significant differences in histological findings of rat liver were observed in paracetamol treated control group (P<0.001), ascorbic acid pretreated and paracetamol treated group (P<0.001). The serum alanine aminotransferase (ALT) level was also significantly higher in paracetamol treated group (P<0.001), α-tocopherol pretreated plus paracetamol treated group (P≤0.05) and in ascorbic acid pretreated plus paracetamol treated group (P<0.001). Conclusion: The combined pretreatment of α-tocopherol & ascorbic acid have better hepatoprotective effects than α-tocopherol or ascorbic acid alone against paracetamol induced liver damage. The decrement of free radicals produced by vitamin E could be a better hepatoprotective antioxidant than vitamin C in paracetamol induced toxicity.

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Combined treatment of ascorbic acid or alpha-tocopherol with dopamine receptor antagonist or nitric oxide synthase inhibitor potentiates cataleptic effect in mice

Psychopharmacology ◽

10.1007/s00213-005-2222-6 ◽

2005 ◽

Vol 181 (1) ◽

pp. 71-79 ◽

Cited By ~ 13

Author(s):

M. Lazzarini ◽

C. Salum ◽

E. A. Del Bel

Keyword(s):

Nitric Oxide ◽

Ascorbic Acid ◽

Nitric Oxide Synthase ◽

Receptor Antagonist ◽

Combined Treatment ◽

Alpha Tocopherol ◽

Nitric Oxide Synthase Inhibitor ◽

Dopamine Receptor Antagonist ◽

Synthase Inhibitor ◽

Oxide Synthase

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Gas phase oxidants of cigarette smoke induce lipid peroxidation and changes in lipoprotein properties in human blood plasma. Protective effects of ascorbic acid

Biochemical Journal ◽

10.1042/bj2770133 ◽

1991 ◽

Vol 277 (1) ◽

pp. 133-138 ◽

Cited By ~ 343

Author(s):

B Frei ◽

T M Forte ◽

B N Ames ◽

C E Cross

Keyword(s):

Lipid Peroxidation ◽

Ascorbic Acid ◽

Blood Plasma ◽

Gas Phase ◽

Cigarette Smoke ◽

Human Blood ◽

Biological Fluids ◽

Human Blood Plasma ◽

Lipid Hydroperoxides ◽

Protein Thiols

Cigarette smoke (CS) is known to contain a large number of oxidants. In order to assess the oxidative effects of CS on biological fluids, we exposed human blood plasma to filtered (gas phase) and unfiltered (whole) CS, and determined the rate of utilization of endogenous antioxidants in relation to the appearance of lipid hydroperoxides. Lipid peroxidation was measured with a specific and sensitive assay that can detect lipid hydroperoxides at plasma levels as low as 10 nM. We found that exposure of plasma to the gas phase of CS, but not to whole CS, induces lipid peroxidation once endogenous ascorbic acid has been oxidized completely. In addition, CS exposure caused oxidation of plasma protein thiols and albumin-bound bilirubin, whereas uric acid and alpha-tocopherol were not consumed at significant rates. In plasma exposed to the gas phase of CS, low-density lipoprotein exhibited slightly increased electrophoretic mobility, but there was no apparent degradation of apolipoprotein B. Our results support the concept of an increased vitamin C utilization in smokers, and suggest that lipid peroxidation induced by oxidants present in the gas phase of CS leads to potentially atherogenic changes in lipoproteins.

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