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

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

doi:10.1016/j.atherosclerosis.2014.10.101

Cited by 29 publications

(19 citation statements)

References 47 publications

(52 reference statements)

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“…The GPx activity in liver, erythrocytes and plasma was measured using a commercial kit (RS504, Randox Laboratories, Crumlin, UK) with samples prepared according to Kader et al [20]. Plasma was diluted in PBS (1 in 20) before GPx activity measurement.…”

Section: Gpx Activitymentioning

confidence: 99%

“…In comparison, ribose-cysteine generates a slower more sustained release of L-cysteine than NAC increasing GSH levels in multiple tissues without any toxicity when administered in a single high dose to mice (2.0 g/kg body weight) [19]. A recent study showed that ribose-cysteine given daily for 8 weeks at a dose of 0.16g/kg/day significantly increased both the liver and plasma GSH levels in a mouse model of hyperlipidaemia without toxicity [20]. Furthermore, this was associated with a significantly increased activity of GPx in the liver and blood and a reduction in the level of oxidised lipids in arteries [20].…”

Section: Introductionmentioning

confidence: 99%

“…A recent study showed that ribose-cysteine given daily for 8 weeks at a dose of 0.16g/kg/day significantly increased both the liver and plasma GSH levels in a mouse model of hyperlipidaemia without toxicity [20]. Furthermore, this was associated with a significantly increased activity of GPx in the liver and blood and a reduction in the level of oxidised lipids in arteries [20].…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2020

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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.

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Section: Gpx Activitymentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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

et al. 2020

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“…Rice is widely consumed around the world and rice-derived peptides are reported to have various biological effects such as anti-microbial activity, (8,9) anti-oxidative activity (10,11) and dipeptidyl peptidase-IV-inhibitory activity. (12,13) Compounds that have so far been reported to increase intracellular glutathione levels include silymarin, (14) cyanohydroxybutene, (15) α-naphthoflavone, (16) apocynin, (17) epalrestat, (18,19) ribose-cysteine, (20) β-carotene, (21) noradrenaline, (22) and lactacystin. (23) In a previous study, we demonstrated that rice-derived peptides (RP), obtained from commercial rice proteins using a commercial protease from Aspergillus oryzae , inhibit dipeptidyl peptidase-IV.…”

Section: Introductionmentioning

confidence: 99%

Hepatoprotective effects of rice-derived peptides against acetaminophen-induced damage in mice

Kawakami

Moritani

Uraji³

et al. 2017

J. Clin. Biochem. Nutr.

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Glutathione, the most abundant intracellular antioxidant, protects cells against reactive oxygen species induced oxidative stress and regulates intracellular redox status. We found that rice peptides increased intracellular glutathione levels in human hepatoblastoma HepG2 cells. Acetaminophen is a commonly used analgesic. However, an overdose of acetaminophen causes severe hepatotoxicity via depletion of hepatic glutathione. Here, we investigated the protective effects of rice peptides on acetaminophen-induced hepatotoxicity in mice. ICR mice were orally administered rice peptides (0, 100 or 500 mg/kg) for seven days, followed by the induction of hepatotoxicity via intraperitoneal injection of acetaminophen (700 mg/kg). Pretreatment with rice peptides significantly prevented increases in serum alanine aminotransferase, aspartate aminotransferase, and lactate dehydrogenase levels and protected against hepatic glutathione depletion. The expression of γ-glutamylcysteine synthetase, a key regulatory enzyme in the synthesis of glutathione, was decreased by treatment with acetaminophen, albeit rice peptides treatment recovered its expression compared to that achieved treatment with acetaminophen. In addition, histopathological evaluation of the livers also revealed that rice peptides prevented acetaminophen-induced centrilobular necrosis. These results suggest that rice peptides increased intracellular glutathione levels and could protect against acetaminophen-induced hepatotoxicity in mice.

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“…In the present study, the systemic redox status in the whole body was estimated by detecting the antioxidant capacity and oxidant production in the liver. As the site for cholesterol metabolism, liver contains a high GSH content and is the major organ involved in its synthesis; GSH depletion is associated with the increased levels of lipid peroxides in the liver [34, 35]. Lipid peroxidation (MDA) and GSH levels are shown in Fig 2B and 2C, respectively.…”

Section: Resultsmentioning

confidence: 99%

CLIC1 Inhibition Attenuates Vascular Inflammation, Oxidative Stress, and Endothelial Injury

Zhu

et al. 2016

PLoS ONE

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Endothelial dysfunction, which includes endothelial oxidative damage and vascular inflammation, is a key initiating step in the pathogenesis of atherosclerosis (AS) and an independent risk factor for this disorder. Intracellular chloride channel 1 (CLIC1), a novel metamorphic protein, acts as a sensor of cell oxidation and is involved in inflammation. In this study, we hypothesize that CLIC1 plays an important role in AS. Apolipoprotein E-deficient mice were supplied with a normal diet or a high-fat and high-cholesterol diet for 8 weeks. Overexpressed CLIC1 was associated with the accelerated atherosclerotic plaque development, amplified oxidative stress, and in vivo release of inflammatory cytokines. We subsequently examined the underlying molecular mechanisms through in vitro experiments. Treatment of cultured human umbilical vein endothelial cells (HUVECs) with H2O2 induced endothelial oxidative damage and enhanced CLIC1 expression. Suppressing CLIC1 expression through gene knocked-out (CLIC1−/−) or using the specific inhibitor indanyloxyacetic acid-94 (IAA94) reduced ROS production, increased SOD enzyme activity, and significantly decreased MDA level. CLIC1−/− HUVECs exhibited significantly reduced expression of TNF-α and IL-1β as well as ICAM-1 and VCAM-1 at the protein levels. In addition, H2O2 promoted CLIC1 translocation to the cell membrane and insertion into lipid membranes, whereas IAA94 inhibited CLIC1 membrane translocation induced by H2O2. By contrast, the majority of CLIC1 did not aggregate on the cell membrane in normal HUVECs, and this finding is consistent with the changes in cytoplasmic chloride ion concentration. This study demonstrates for the first time that CLIC1 is overexpressed during AS development both in vitro and in vivo and can regulate the accumulation of inflammatory cytokines and production of oxidative stress. Our results also highlight that deregulation of endothelial functions may be associated with the membrane translocation of CLIC1 and active chloride-selective ion channels in endothelial cells.

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

Cited by 29 publications

References 47 publications

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

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

Hepatoprotective effects of rice-derived peptides against acetaminophen-induced damage in mice

CLIC1 Inhibition Attenuates Vascular Inflammation, Oxidative Stress, and Endothelial Injury

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