Atherosclerosis 2014-12-01

Ribose-cysteine increases glutathione-based antioxidant status and reduces LDL in human lipoprotein(a) mice.

Tanjina Kader, Carolyn M Porteous, Michael J A Williams, Steven P Gieseg, Sally P A McCormick

Index: Atherosclerosis 237(2) , 725-33, (2014)

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Abstract

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.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.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).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.Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.