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

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 (GP x), the redox enzyme that catalyses the reduction of lipid peroxides. A low GP x 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, GP. x, lipid oxidation products and plasma lipids invivo. Methods: Human lipoprotein(a) [Lp(a)] transgenic mice were treated with 4mg/day ribose-cysteine (0.16g/kg body weight) for 8 weeks. Livers and blood were harvested from treated and untreated controls (n=9 per group) and GSH concentrations, GP x 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). GP. x 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.