Antioxidant activities of probucol against lipid peroxidations

Goton, Naohiro; Shimizu, Kyoko; Komuro, Erika; Tsuchiya, Jyunichi; Noguchi, Noriko; Niki, Etsuo

doi:10.1016/0005-2760(92)90300-k

Cited by 84 publications

(36 citation statements)

References 35 publications

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“…As is known, a-tocopherol and BHA act as radical chain blockers by scavenging hydroxyl and lipid peroxyl radicals generated in the membrane lipid layers. 32,33) From these results, it is suggested that intracellular ROS production may be an important mechanism of the onset of Al toxicity. In addition, the lack of prevention of Al(maltol) 3 -induced ROS production or cell death by the addition of DFO indicates that ironmediated extracellular Fe 2ϩ -induced ROS production and/or lipid peroxidation of the membrane lipids are not directly involved in the onset of Al(maltol) 3 -induced cell death.…”

Section: Fig 6 Effects Of Nac and Other Antioxidants On Ros Productionmentioning

confidence: 96%

Glutathione Depletion Promotes Aluminum-Mediated Cell Death of PC12 Cells

Satoh

Okada

Takadera

et al. 2005

Biological & Pharmaceutical Bulletin

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Section: Fig 6 Effects Of Nac and Other Antioxidants On Ros Productionmentioning

confidence: 96%

Glutathione Depletion Promotes Aluminum-Mediated Cell Death of PC12 Cells

Satoh

Okada

Takadera

et al. 2005

Biological & Pharmaceutical Bulletin

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“…5,6) In vitro and in vivo studies have demonstrated that the antioxidant potential of probucol is comparable to or even higher than that of well-known antioxidant vitamin E, the advantage of the former being its higher lipophilicity and tendency to concentrate in cellular membranes, efficiently protecting them against damage caused by lipid peroxidation. 7,8) The addition of probucol to candesartan normalized urinary protein excretion, glomerular cell number and glomerulosclerosis, and completely eliminated reduced nicotinamide adenine dinucleotide phosphate (NADPH) oxidase-associated reactive oxygen species (ROS) production in rat progressive mesangioproliferative glomerulonephritisin. 9) Probucol suppressed oxidative stress and improve glomerulosclerosis in the kidneys of streptozotocin (STZ) induced type 1 diabetic rats.…”

mentioning

confidence: 99%

Probucol Inhibited Nox2 Expression and Attenuated Podocyte Injury in Type 2 Diabetic Nephropathy of db/db Mice

Zhou

Wang

et al. 2013

Biological & Pharmaceutical Bulletin

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The present study was conducted to investigate the effects of probucol on the progression of diabetic nephropathy and the underlying mechanism in type 2 diabetic db/db mice. Eight weeks db/db mice were treated with regular diet or probucol-containing diet (1%) for 12 weeks. Non-diabetic db/m mice were used as controls. We examined body weight, blood glucose, and urinary albumin. At 20 weeks, experimental mice were sacrificed and their blood and kidneys were extracted for the analysis of blood chemistry, kidney histology, oxidative stress marker, and podocyte marker. As a result, 24 h urinary albumin excretions were reduced after probucol treatment. There were improvements of extracellular matrix accumulation and fibronectin and collagen IV deposition in glomeruli in the probucol-treated db/db mice. The reduction of nephrin and the loss of podocytes were effectively prevented by probucol in db/db mice. Furthermore, probucol significantly decreased the production of thiobarbituric acid-reactive substances (TBARS), an index of reactive oxygen species (ROS) generation and down-regulated the expression of Nox2. Taken together, our findings support that probucol may have the potential to protect against type 2 diabetic nephropathy via amelioration of podocyte injury and reduction of oxidative stress.

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“…The transgenic mice for ABCA1 had a significant increase in plasma HDL (16,17). These results indicate that this protein is a regulating factor for the plasma HDL level through generation of HDL by the apolipoproteincell interaction.Probucol has been clinically used as an antiatherogenic compound, not only because of its lipid-lowering effect but also because of the hypothesis that its antioxidative nature prevents atherogenic oxidative modification of low density lipoprotein (LDL) shown by in vitro (18,19) and in vivo models (20, 21). However, probucol substantially reduces plasma HDL (22).…”

mentioning

confidence: 99%

“…Probucol has been clinically used as an antiatherogenic compound, not only because of its lipid-lowering effect but also because of the hypothesis that its antioxidative nature prevents atherogenic oxidative modification of low density lipoprotein (LDL) shown by in vitro (18,19) and in vivo models (20, 21). However, probucol substantially reduces plasma HDL (22).…”

mentioning

confidence: 99%

Probucol Inactivates ABCA1 in the Plasma Membrane with Respect to Its Mediation of Apolipoprotein Binding and High Density Lipoprotein Assembly and to Its Proteolytic Degradation

Chengai

Tsujita

Hayashi

et al. 2004

Journal of Biological Chemistry

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Probucol has been shown to inhibit the release of cellular lipid by helical apolipoprotein and thereby to reduce plasma high density lipoprotein. We attempted to explore the underlying mechanism for this effect in human fibroblast WI-38. Probucol inhibited the apoA-Imediated cellular lipid release and binding of apoA-I to the cells in a dose-dependent manner. It did not influence cellular uptake of low density lipoprotein, transport of cholesterol to the cell surface whether de novo synthesized or delivered as low density lipoprotein, and overall cellular content of cholesterol, although biosynthesis of lipids from acetate was somewhat increased. Probucol did not affect the mRNA level of ABCA1, and ABCA1 was recovered along with marker proteins for plasma membrane regardless of the presence of probucol. However, the protein level of ABCA1 increased, and the rate of its decay in the presence of cycloheximide was slower in the probucol-treated cells. ABCA1 in the probucol-treated cells was resistant to digestion by calpain but not by trypsin. We concluded that probucol inactivates ABCA1 in the plasma membrane with respect to its function in mediating binding of and lipid release by apolipoprotein and with respect to proteolytic degradation by calpain.Cholesterol is an essential molecule for animal cells to maintain and regulate function and structure of the biomembrane. It is synthesized in most somatic cells, whereas its catabolic site is limited to the liver and to the steroidogenic cells except for partial hydroxylation in some somatic cells. Accordingly, cholesterol is removed from the cells and transported to the liver for its conversion to bile acids, and this is one of the essential events in cholesterol homeostasis for the body and for the cells (1). High density lipoprotein (HDL) 1 is believed to play a central role in this system, and this is thought to be one of the antiatherogenic characteristics of HDL. This reaction takes place through at least two distinct mechanisms: 1) physicochemical release of cholesterol from the cell surface, which is driven by cholesterol esterification on HDL, and 2) the apolipoprotein-mediated pathway to remove cellular cholesterol and phospholipid to generate new HDL particles (2). HDL thus plays a central role in both mechanisms.Apolipoprotein-dependent cellular cholesterol release is absent in fibroblasts from patients with Tangier disease (3, 4), and mutations in the gene encoding the ATP-binding cassette transporter A1 (ABCA1) are the underlying cause of this disease (5-9). On the other hand, in vitro overexpression of functional ABCA1 in the cells (10, 11) and induction of ABCA1 expression by cyclic AMP analogues (12, 13) or by the ligands for the liver X receptor or retinoid X receptor (14, 15) enhanced the release of cellular cholesterol and phospholipid by apolipoprotein. The transgenic mice for ABCA1 had a significant increase in plasma HDL (16,17). These results indicate that this protein is a regulating factor for the plasma HDL level through generation of HDL b...

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Antioxidant activities of probucol against lipid peroxidations

Cited by 84 publications

References 35 publications

Glutathione Depletion Promotes Aluminum-Mediated Cell Death of PC12 Cells

Glutathione Depletion Promotes Aluminum-Mediated Cell Death of PC12 Cells

Probucol Inhibited Nox2 Expression and Attenuated Podocyte Injury in Type 2 Diabetic Nephropathy of db/db Mice

Probucol Inactivates ABCA1 in the Plasma Membrane with Respect to Its Mediation of Apolipoprotein Binding and High Density Lipoprotein Assembly and to Its Proteolytic Degradation

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