Open AccessRibose-cysteine protects against the development of atherosclerosis in apoE-deficient mice
Author(s) -
Tanjina Kader,
Carolyn M. Porteous,
Gregory Todd Jones,
Nina Dickerhof,
Vinod K. Narayana,
Dedreia Tull,
Sreya Taraknath,
Sally P.A. McCormick
Publication year - 2020
Publication title -
plos one
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.99
H-Index - 332
ISSN - 1932-6203
DOI - 10.1371/journal.pone.0228415
Subject(s) - glutathione , apolipoprotein e , medicine , endocrinology , chemistry , glutathione peroxidase , cysteine , lipoprotein , apolipoprotein b , cholesterol , biochemistry , enzyme , disease
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.