Ribose-cysteine protects against the development of atherosclerosis in apoE-deficient mice

PLoS One. 2020 Feb 21;15(2):e0228415. doi: 10.1371/journal.pone.0228415. eCollection 2020.


Ribose-cysteine is a synthetic compound designed to increase glutathione (GSH) synthesis. Low levels of GSH and the GSH-dependent enzyme, glutathione peroxidase (GPx), is associated with cardiovascular disease (CVD) in both mice and humans. Here we investigate the effect of ribose-cysteine on GSH, GPx, oxidised lipids and atherosclerosis development in apolipoprotein E-deficient (apoE-/-) mice. Female 12-week old apoE-/- mice (n = 15) were treated with 4-5 mg/day ribose-cysteine in drinking water for 8 weeks or left untreated. Blood and livers were assessed for GSH, GPx activity and 8-isoprostanes. Plasma alanine transferase (ALT) and lipid levels were measured. Aortae were quantified for atherosclerotic lesion area in the aortic sinus and brachiocephalic arch and 8-isoprostanes measured. Ribose-cysteine treatment significantly reduced ALT levels (p<0.0005) in the apoE-/- mice. Treatment promoted a significant increase in GSH concentrations in the liver (p<0.05) and significantly increased GPx activity in the liver and erythrocytes of apoE-/-mice (p<0.005). The level of 8-isoprostanes were significantly reduced in the livers and arteries of apoE-/- mice (p<0.05 and p<0.0005, respectively). Ribose-cysteine treatment showed a significant decrease in total and low density lipoprotein (LDL) cholesterol (p<0.05) with no effect on other plasma lipids with the LDL reduction likely through upregulation of scavenger receptor-B1 (SR-B1). Ribose-cysteine treatment significantly reduced atherosclerotic lesion area by >50% in both the aortic sinus and brachiocephalic branch (p<0.05). Ribose-cysteine promotes a significant GSH-based antioxidant effect in multiple tissues as well as an LDL-lowering response. These effects are accompanied by a marked reduction in atherosclerosis suggesting that ribose-cysteine might increase protection against CVD.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antioxidants / administration & dosage*
  • Antioxidants / metabolism
  • Apolipoproteins E / deficiency*
  • Atherosclerosis / metabolism
  • Atherosclerosis / pathology
  • Atherosclerosis / prevention & control*
  • Cysteine / administration & dosage*
  • Cysteine / metabolism
  • Female
  • Lipids / analysis
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout, ApoE
  • Oxidation-Reduction
  • Protective Agents / administration & dosage*
  • Protective Agents / metabolism
  • Ribose / administration & dosage*
  • Ribose / metabolism


  • Antioxidants
  • Apolipoproteins E
  • Lipids
  • Protective Agents
  • Ribose
  • Cysteine

Grants and funding

This study was supported by funding from Max International, LLC, Salt Lake City, UT, USA who provided the ribose-cysteine and by an Otago School of Medical Sciences Bequest Fund. ST was supported by an Otago Postgraduate Research Scholarship.