Highlights
- •We tested the in vivo effect of ribose-cysteine on glutathione and plasma lipids.
- •Ribose-cysteine increased GSH and GPx activity and lowered oxidised lipids.
- •Ribose-cysteine significantly decreased LDL, apoB and Lp(a) levels.
- •Ribose-cysteine might be an ideal intervention to increase protection against CVD.
Abstract
Objective: d-ribose-l-cysteine (ribose-cysteine) is a cysteine analogue designed to increase the synthesis
of glutathione (GSH). GSH is a cofactor for glutathione peroxidase (GPx), the redox enzyme that catalyses the reduction of lipid peroxides. A low GPx activity and increased oxidised lipids are associated with the development of cardiovascular
disease (CVD). Here we aimed to investigate the effect of ribose-cysteine supplementation
on GSH, GPx, lipid oxidation products and plasma lipids in vivo. Methods: Human lipoprotein(a) [Lp(a)] transgenic mice were treated with 4 mg/day ribose-cysteine
(0.16 g/kg body weight) for 8 weeks. Livers and blood were harvested from treated
and untreated controls (n = 9 per group) and GSH concentrations, GPx activity, thiobarbituric acid reactive substances (TBARS), 8-isoprostanes and plasma
lipid concentrations were measured. Results: Ribose-cysteine increased GSH concentrations in the liver and plasma (P < 0.05). GPx activity was increased in both liver (1.7 fold, P < 0.01) and erythrocytes (3.5 fold, P < 0.05). TBARS concentrations in the liver, plasma and aortae were significantly
reduced with ribose-cysteine (P < 0.01, P < 0.0005 and P < 0.01, respectively) as were the concentrations of 8-isoprostanes in the liver and
aortae (P < 0.0005, P < 0.01, respectively). Ribose-cysteine treated mice showed significant decreases
in LDL, Lp(a) and apoB concentrations (P < 0.05, P < 0.01 and P < 0.05, respectively), an effect which was associated with upregulation of the LDL
receptor (LDLR).Conclusions: As ribose-cysteine lowers LDL, Lp(a) and oxidised lipid concentrations, it might
be an ideal intervention to increase protection against the development of atherosclerosis.
Keywords
Abbreviations:
CVD (cardiovascular disease), Lp(a) (lipoprotein(a)), LDL (low density lipoprotein), HDL (high density lipoprotein), TG (triglycerides), apoB (apolipoproteinB-100), GSH (glutathione), GPx (glutathione peroxidase), TBARS (thiobarbituric acid reactive substances)To read this article in full you will need to make a payment
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References
- Atherosclerosis.Nature. 2000; 407: 233-241
- A population at risk. Prevalence of high cholesterol levels in hypertensive patents in the framingham study.Am. J. Med. 1986; 80: 23-32
- Lipoprotein(a) concentration and the risk of coronary heart disease, stroke, and nonvascular mortality.JAMA. 2009; 302: 412-423
- Oxidized phospholipids predict the presence and progression of carotid and femoral atherosclerosis and symptomatic cardiovascular disease.J. Am. Coll. Cardiol. 2006; 47: 2219-2228
- Relationship of oxidized phospholipids on apolipoprotein B-100 particles to race/ethnicity, apolipoprotein(a) isoform size, and cardiovascular risk factors: results from the dallas heart study.Circulation. 2009; 119: 1711-1719
- Glutathione peroxidase-1 in health and disease: from molecular mechanism to therapeutic opportunities.Antioxid. Redox Signal. 2011; 15: 1957-1983
- Mechanistic aspects of enhanced lipid peroxidation following glutathione depletion in vivo.Chem. Biol. Interact. 1981; 34: 257-266
- Impact of glutathione peroxidase-1 deficiency on macrophage foam cell formation and proliferation: implications for atherogenesis.PLoS ONE. 2013; 8: e72063
- Glutathione peroxidase 1 activity and cardiovascular events in patients with coronary artery disease.N. Engl. J. Med. 2003; 349: 1605-1613
- Low serum glutathione peroxidase activity is associated with increased cardiovascular mortality in individuals with low HDLc's.PLoS ONE. 2012; 7: e38901
- Glutathione synthesis.Biochimica Biophysica Acta. 2013; 1830: 3143-3153
- The regulation of hepatic glutathione.Ann. Rev. Pharmacol. Toxicol. 1985; 25: 715-744
- Quantitative nutritional studies with water-soluble, chemically defined diets. III. Individual amino acids as sources of “non-essential” nitrogen.Arch. Biochem. Biophys. 1957; 72: 428-436
- Antioxidant properties of N-acetylcysteine: their relevance in relation to chronic obstructive pulmonary disease.Eur. Respir. J. 2004; 23: 629-636
- N-acetylcysteine inhibits platelet-monocyte conjugation in patients with type 2 diabetes with depleted intraplatelet glutathione: a randomised controlled trial.Diabetologia. 2012; 55: 2920-2928
- Paracetamol (acetaminophen) poisoning.Lancet. 1995; 346: 547-552
- Prodrugs of L-cysteine as protective agents against acetaminophen-induced hepatotoxicity. 2-(polyhydroxyalkyl)-and 2-(polyacetoxyalkyl)thiazolidine-4(R)-carboxylic acids.J. Med. Chem. 1987; : 1891-1896
- Mechanisms of chemoprotection by RibCys, a thiazolidine prodrug of L-cysteine.Med. Chem. Res. 1991; 1: 213-219
- Time course for the elevation of glutathione in numerous organs of L1210-bearing CDF1 mice given the L-cysteine prodrug, RibCys.Toxicol. Lett. 1991; 59: 245-251
- Transgenic mice expressing high plasma concentrations of human apolipoprotein B100 and lipoprotein(a).J. Clin. Invest. 1993; 92: 3029-3037
- Reconstitution of lipoprotein(a) by infusion of human low density lipoprotein into transgenic mice expressing human apolipoprotein(a).J. Biol. Chem. 1992; 267: 24369-24374
- Methodologies for the application of monobromobimane to the simultaneous analysis of soluble and protein thiol components of biological systems.J. Biochem. Biophys. Methods. 1986; 13: 231-249
- The generation of superoxide radicals during the auto-oxidation of hemoglobin.J. Biol. Chem. 1972; 247: 6960-6962
- Fluorometric and colourimetric assessment of thiobarbituric acid-reactive lipid aldehydes in biological matrices.in: Hensley K. Floyd R.A. Methods in pharmacology and toxicology: methods in biological oxidative stress. Humana Press Inc, Totowa NJ, USA2003
- Hepatic expression of microsomal triglyceride transfer protein and in vivo secretion of triglyceride-rich lipoproteins are increased in obese diabetic mice.Diabetes. 2002; 51: 1233-1239
- Transgenic mice expressing high levels of human apolipoprotein B develop severe atherosclerotic lesions in response to a high-fat diet.J. Clin. Invest. 1995; 95: 2246-2257
- Estimation of the concentration of low-density lipoprotein cholesterol in plasma, without use of the preparative ultracentrifuge.Clin. Chem. 1972; 18: 499-502
- Effect of the number of apolipoprotein(a) kringle 4 domains on immunochemical measurements of lipoprotein(a).Clin. Chem. 1995; 41: 246-255
- Use of bacterial expression cloning to localize the epitopes for a series of monoclonal antibodies against apolipoprotein B100.J. Biol. Chem. 1990; 265: 553-568
- Protection against acetaminophen hepatotoxicity by ribose-cysteine (Rib-Cys).Pharmacol. Toxicol. 1992; 70: 281-285
- Ribose cysteine protects against acetaminophen-induced hepatic and renal toxicity.Toxicol. Pathol. 2000; 28: 697-704
- Five cysteine-containing compounds have antioxidative activity in Balb/cA Mice.J. Nutr. 2004; 134: 149-152
- Effect of N-acetylcysteine administration on the expression and activities of antioxidant enzymes and the malondialdehyde level in the blood of lead-exposed workers.Environ. Toxicol. Pharmacol. 2014; 37: 638-647
- The relationship between plasma triglycerides, cholesterol, total lipids and lipid peroxidation products during human atherosclerosis.Clin. Chim. Acta. 1986; 155: 275-284
- Is oxidative stress causally linked to unstable angina pectoris? A study in 100 CAD patients and matched controls.Cardiovasc. Res. 1997; 36: 330-336
- Lipid peroxidation in hyperlipidaemic patients. A study of plasma using an HPLC-based thiobarbituric acid test.Free Rad. Res. Comms. 1993; 19: 51-57
- The isoprostanes: unique bioactive products of lipid peroxidation.Prog. Lipid Res. 1997; 36: 1-21
- Hold the antioxidants and improve plasma lipids?.J. Clin. Invest. 2004; 113: 1253-1255
- Why does plasma low density lipoprotein concentration in adults increase with age?.Lancet. 1984; 323: 263-267
- Quercetin up-regulates LDL receptor expression in HepG2 cells.Phytother. Res. 2012; 26: 1688-1694
- Effects of cysteine containing compounds on biosynthesis of triacylglycerol and cholesterol and anti-oxidative protection in liver from mice consuming a high-fat diet.Br. J. Nutr. 2008; 99: 37-43
- Lipoprotein(a) reduction by N-Acetylcysteine.Lancet. 1991; 337: 203-204
- Acute phase reactants as novel predictors of cardiovascular disease.ISRN Inflamm. 2012; 2012: 1-18
- Overexpression of human low density lipoprotein receptors leads to accelerated catabolism of Lp(a) lipoprotein in transgenic mice.J. Clin. Invest. 1990; : 1542-1547
- Lipoprotein(a) metabolism: potential sites for therapeutic targets.Metabolism. 2012; : 1-13
- MRC/BHF heart protection study of antioxidant vitamin supplementation in 20,536 high-risk individuals: a randomised placebo-controlled trial.Lancet. 2002; 360: 23-33
- Mechanisms of HDL reduction after probucol. Changes in HDL subfractions and increased reverse cholesteryl ester transfer.Arterioscler. Thromb. Vasc. Biol. 1989; 9: 462-469
Article info
Publication history
Published online: November 01, 2014
Accepted:
October 31,
2014
Received in revised form:
October 30,
2014
Received:
June 6,
2014
Identification
Copyright
© 2014 Elsevier Ireland Ltd. Published by Elsevier Inc. All rights reserved.