Protective effects of D-glucaro 1,4-lactone against oxidative/nitrative modifications of plasma proteins

doi:10.1016/j.nut.2006.11.003

Nutrition

Volume 23, Issue 2, February 2007, Pages 164-171

https://doi.org/10.1016/j.nut.2006.11.003 Get rights and content

Abstract

Objective

The protective effects of D-glucaro 1,4-lactone (1,4-GL) against oxidative/nitrative protein damage (determined by parameters such as levels of protein carbonyl groups and nitrotyrosine residues) to human plasma treated with peroxynitrite (ONOO⁻) or hydroperoxide (H₂O₂) were studied in vitro. We also investigated the effects of 1,4-GL on the level of total free thiol groups and low-molecular-weight thiols (glutathione and homocysteine) in plasma treated with ONOO⁻ (0.1 mM).

Methods

Levels of carbonyl groups and nitrotyrosine residues in human plasma proteins were measured by ELISA and a competition ELISA, respectively. High-performance liquid chromatography (HPLC) was used to analyze free thiols from plasma.

Results

Exposure of plasma to ONOO⁻ (0.1 mM) resulted in an increase of the level of carbonyl groups and nitrotyrosine residues in plasma proteins and in a distinct decrease in total thiols and low-molecular-weight thiols (glutathione and homocysteine) measured by high-performance liquid chromatography. In the presence of 1,4-GL (0.4–6.4 mM), a distinct decrease in carbonyl group formation and tyrosine nitration in plasma proteins and changes in plasma thiols caused by 0.1 mM of peroxynitrite were observed. Moreover, 1,4-GL inhibited plasma protein oxidation induced by H₂O₂ (2 mM).

Conclusion

The obtained results indicate that in vitro 1,4-GL has inhibitory effects on ONOO⁻- or hydroperoxide-mediated oxidative stress in human plasma and changes plasma redox thiol status. The mechanism of the antioxidative action of 1,4-GL present in plasma is not known yet.

Introduction

D-glucaro 1,4-lactone (1,4-GL) is formed in the gastrointestinal tract from D-glucaric acid or its salts and is transported to blood where it can have effects on blood components [1]. D-glucaric acid is a natural, non-toxic compound found in large amounts in many different fruits and vegetables, with the highest concentrations in oranges, apples, grapefruits, and cruciferous vegetables; it also may be produced in small amounts by mammals (including humans) [2]. 1,4-GL possesses detoxifying and anticarcinogenic properties, attributed to an ability to increase glucuronidation and excretion of potentially toxic compounds [3]. 1,4-GL with some biological properties is the most pharmacologically active metabolite of D-glucaric acid. It is a β-glucuronidase inhibitor [4]. The aim of the present study was to estimate the direct effects of 1,4-GL on changes induced by strong biological oxidants, i.e., peroxynitrite (ONOO⁻) and hydroperoxide (H₂O₂), in plasma proteins and on the level of total free thiol groups and low-molecular-weight thiols such as glutathione and homocysteine (HCSH) in plasma. The defense mechanisms against oxidative stress (ONOO⁻ and H₂O₂ action) are very important for biological activities of human plasma components. Moreover, the role of exogenous antioxidants (present in the human diet) in the defense against oxidative stress in human plasma is still unknown. Therefore, the protective effects of 1,4-GL against the oxidative/nitrative damage of human plasma proteins and low-molecular-weight thiols (glutathione and HCSH as important components of plasma redox thiol status) induced by ONOO⁻ (0.1 mM) and H₂O₂ (2 mM) were studied. The concentration of ONOO⁻ used in our experiments was relatively high. The lifetime of ONOO⁻ at physiologic pH is very short, with its half-time being of the order of 1 s. Exposure to a bolus of 250 μM of ONOO⁻ is equivalent to 7 min of exposure to a steady-state ONOO⁻ concentration of 1 μM. This concentration could be readily formed at sites of inflammation, where production rates of nitric oxide radicals (NO^•) and superoxide radicals considerably increase [5].

Section snippets

Materials

Peroxynitrite was synthesized according to the method of Pryor and Squadrito [6]. Freeze fractionation (−70°C) of the peroxynitrite solution formed a yellow top layer, which was retained for further studies. The top layer typically contained 80–100 mM of peroxynitrite as determined spectrophotometrically at 302 nm in 0.1 M of NaOH (ϵ_302nm = 1679 M/cm). Some experiments were also performed with decomposed ONOO⁻, which was prepared by allowing the ONOO⁻ to decompose at neutral pH (7.4) in 100 mM

Results

Our studies showed that 1,4-GL decreased the oxidation of plasma proteins (measured as the level of carbonyl groups by ELISA) caused by treatment of plasma with two different strong oxidants (2 mM of H₂O₂ or 0.1 mM of ONOO⁻). The decrease induced by 1,4-GL was statistically significant (P < 0.05; Fig. 1) and inhibition was dose dependent. 1,4-GL at the highest concentration (6.4 mM) decreased carbonyl group formation in plasma proteins treated with ONOO⁻ (0.1 mM) by approximately 40% (Fig. 1).

Discussion

Proteins may be the initial targets of reactive oxygen species or reactive nitrogen species (ROS/RNS) [14], [15]. It has been demonstrated that reaction of proteins with ROS/RNS results in the oxidation and nitration of some amino acid residues, loss of protein thiol groups, formation of aggregates, or fragmentation of proteins. In oxidized proteins new carbonyl groups and protein hydroperoxides are also formed. Among the various oxidative modifications of proteins, formation of carbonyl groups

References (51)

Z. Walaszek
Potential use of D-glucaric acid derivatives in cancer prevention
Cancer Lett
(1990)
Z. Walaszek et al.
D-glucaric acid content of various fruits and vegetables and cholesterol-lowering effects of dietary D-glucarate in the rat
Nutr Res
(1996)
D. Horton et al.
Conformations of the D-glucarolactones and D-glucaric acid in solution
Carbohydr Res
(1982)
B. Olas et al.
Protective effects of resveratrol against oxidative/nitrative modifications of plasma proteins and lipids exposed to peroxynitrite
J Nutr Biochem
(2006)
H. Buss et al.
Protein carbonyl measurement by a sensitive ELISA method
Free Radic Biol Med
(1997)
R. Glowacki et al.
Facile and sensitive method for the determination of mesna in plasma by high-performance liquid chromatography with ultraviolet detection
J Chromatogr
(2001)
E. Bald et al.
Analysis of plsama thiols by high-performance liquid chromatography with ultraviolet detection
J Chromatogr
(2004)
G. Lupidi et al.
Peroxynitrite-mediated oxidation of fibrinogen inhibits clot formation
FEBS Lett
(1999)
C. Vadseth et al.
Pro-throbotic state induced by post-translational modification of fibrinogen by reactive nitrogen species
J Biol Chem
(2004)
I. Dalle-Donne et al.
Protein carbonyl groups as biomarkers of oxidative stress
Clin Chim Acta
(2003)

C.D. Reiter et al.

Superoxide reacts with nitric oxide to nitrate tyrosine at physiological pH via peroxynitrite

J Biol Chem

(2000)

H. Ischiropoulos et al.

Peroxynitrite-mediated oxidative protein modifications

FEBS Lett

(1995)

H. Ischiropoulos

Biological tyrosine nitration: a pathophysiological function of nitric oxide

Arch Biochem Biophys

(1998)

H. Ischiropoulos

Biological selectivity and functional aspects of protein tyrosine nitration

Biochem Biophys Res Commun

(2003)

R. Radi et al.

Peroxynitrite-induced membrane lipid peroxidation; the cytotoxic potential of superoxide and nitric oxide

Arch Biochem Biophys

(1991)

B. Olas et al.

The effects of antioxidants on peroxynitrite-induced changes in platelet proteins

Thromb Res

(2004)

E. Mayer et al.

Homocysteine and coronary atherosclerosis

J Am Coll Cardiol

(1996)

X. Yang et al.

Plasma homocysteine thiolactone adducts associated with risk of coronary heart disease

Clin Chim Acta

(2006)

C.A. Elliger et al.

Caffeyi esters of glucaric acid in Lycopersicon esculentum leaves

Phytochemistry

(1981)

B. Risch et al.

(E)-O-p-cumaroyl-, (E)-O-feruloyl-derivatives of glucaric acid in citrus

Phytochemistry

(1988)

G. Kessler et al.

Metabolism of D-glucuronic acid and D-galacturonic acid in Phaseolus aureus seedlings

J Biol Chem

(1961)

G.A. Levvy et al.

β-Glucuronidase and the hydrolysis of glucuronides

F.J. Dowell et al.

The effects of peroxynitrite on rat aorta: interaction with glucose and related substances

Eur J Pharmacol

(1997)

C.L. Hawkins et al.

Direct detection and identification of radicals generated during the hydroxyl radical-induced degradation of hyaluronana and related materials

Free Radic Biol Med

(1996)

M. Hanausek et al.

Detoxifying cancer causing agents to prevent cancer

Integr Cancer Ther

(2003)

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: This work is supported by the grant 506/810 from the University of Lodz.

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Basic nutritional investigationProtective effects of D-glucaro 1,4-lactone against oxidative/nitrative modifications of plasma proteins

Abstract

Objective

Methods

Results

Conclusion

Introduction

Section snippets

Materials

Results

Discussion

Cancer Lett

Nutr Res

Carbohydr Res

J Nutr Biochem

Free Radic Biol Med

J Chromatogr

J Chromatogr

FEBS Lett

J Biol Chem

Clin Chim Acta

J Biol Chem

FEBS Lett

Arch Biochem Biophys

Biochem Biophys Res Commun

Arch Biochem Biophys

Thromb Res

J Am Coll Cardiol

Clin Chim Acta

Phytochemistry

Phytochemistry

J Biol Chem

Eur J Pharmacol

Free Radic Biol Med

Detoxifying cancer causing agents to prevent cancer

Integr Cancer Ther

Basic nutritional investigation
Protective effects of D-glucaro 1,4-lactone against oxidative/nitrative modifications of plasma proteins