title: Ribose-cysteine increases glutathione-based antioxidant status and reduces LDL in human lipoprotein(a) mice.
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.
authors.affiliation: Department of Biochemistry, Otago School of Medical Sciences, University of Otago, Dunedin, New Zealand.
authors.forename: Tanjina
authors.initials: T
authors.lastname: Kader
authors.affiliation: Department of Biochemistry, Otago School of Medical Sciences, University of Otago, Dunedin, New Zealand.
authors.forename: Carolyn M
authors.initials: CM
authors.lastname: Porteous
authors.affiliation: Department of Medicine, Dunedin School of Medicine, University of Otago, Dunedin, New Zealand.
authors.forename: Michael J A
authors.initials: MJ
authors.lastname: Williams
authors.affiliation: School of Biological Sciences, University of Canterbury, Christchurch, New Zealand.
authors.forename: Steven P
authors.initials: SP
authors.lastname: Gieseg
authors.affiliation: Department of Biochemistry, Otago School of Medical Sciences, University of Otago, Dunedin, New Zealand. Electronic address: sally.mccormick@otago.ac.nz.
authors.forename: Sally P A
authors.initials: SP
authors.lastname: McCormick
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000737:chemistry*; D001055:Apolipoproteins B / Q000097:blood; D002318:Cardiovascular Diseases / Q000378:metabolism; D003545:Cysteine / Q000737:chemistry*; D015237:Dinoprost / Q000031:analogs & derivatives / Q000737:chemistry; D005260:Female; D005978:Glutathione / Q000737:chemistry*; D006801:Humans; D008055:Lipids / Q000097:blood; D017270:Lipoprotein(a) / Q000235:genetics* / Q000378:metabolism; D008077:Lipoproteins, LDL / Q000097:blood*; D008099:Liver / Q000378:metabolism; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D010100:Oxygen / Q000737:chemistry; D012266:Ribose / Q000737:chemistry*; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism
chemical_list: D000975:Antioxidants; D001055:Apolipoproteins B; D008055:Lipids; D017270:Lipoprotein(a); D008077:Lipoproteins, LDL; D017392:Thiobarbituric Acid Reactive Substances; C075750:8-epi-prostaglandin F2alpha; D012266:Ribose; D015237:Dinoprost; D005978:Glutathione; D003545:Cysteine; D010100:Oxygen
keywords: CVD; GPx; GSH; LDL; Oxidised lipids; Ribose-cysteine; apoB