Antioxidant probucol as an effective scavenger of lipid radicals in low density lipoproteinsin vivo andin vitro

Tikhaze, A. K.; Lankin, B. Z.; Konovalova, G. G.; Шумаев, К. Б.; Kaminnyi, A. I.; Kozachenko, A. I.; Gurevich, S. M.; Nagler, L. G.; Zaitseva, T. M.; Кухарчук, В. В.

doi:10.1007/bf02433824

Cited by 8 publications

(2 citation statements)

References 13 publications

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“…At the same time, it has been shown that administration of α-TOH at high doses has no effect on LDL oxidizability in CHD patients in vivo [ 101 ]. Thus, it should be recognized that the use of α-TOH to inhibit LDL oxidizability in clinical trials is not justified and the use of coenzyme Q [ 6 , 100 ] and other phenolic antioxidants, in particular probucol [ 6 , 101 , 108 , 109 , 110 ], whose effectiveness in inhibiting LDL oxidation is convincingly confirmed, is more correctly for LDL protection against oxidation [ 6 , 101 ]. It is also clear that it is unacceptable to use data about the “negative” results obtained with individual antioxidants, such as α-TOH and β-carotene [ 92 , 93 , 94 ], for the entire group of antioxidants [ 80 ], which includes a large number of substances with very different structures and mechanisms of action.…”

Section: Antioxidants In Cardiology: Pro Et Contramentioning

confidence: 99%

Dicarbonyl-Dependent Modification of LDL as a Key Factor of Endothelial Dysfunction and Atherosclerotic Vascular Wall Damage

2022

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The review presents evidence that the main damage to the vascular wall occurs not from the action of “oxidized” LDL, which contain hydroperoxy acyls in the phospholipids located in their outer layer, but from the action of LDL particles whose apoprotein B-100 is chemically modified with low molecular weight dicarbonyls, such as malondialdehyde, glyoxal, and methylglyoxal. It has been argued that dicarbonyl-modified LDL, which have the highest cholesterol content, are particularly “atherogenic”. High levels of dicarbonyl-modified LDL have been found to be characteristic of some mutations of apoprotein B-100. Based on the reviewed data, we hypothesized a common molecular mechanism underlying vascular wall damage in atherosclerosis and diabetes mellitus. The important role of oxidatively modified LDL in endothelial dysfunction is discussed in detail. In particular, the role of the interaction of the endothelial receptor LOX-1 with oxidatively modified LDL, which leads to the expression of NADPH oxidase, which in turn generates superoxide anion radical, is discussed. Such hyperproduction of ROS can cause destruction of the glycocalyx, a protective layer of endotheliocytes, and stimulation of apoptosis in these cells. On the whole, the accumulated evidence suggests that carbonyl modification of apoprotein B-100 of LDL is a key factor responsible for vascular wall damage leading to atherogenesis and endothelial dysfunction. Possible ways of pharmacological correction of free radical processes in atherogenesis and diabetogenesis are also discussed.

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Section: Antioxidants In Cardiology: Pro Et Contramentioning

confidence: 99%

Dicarbonyl-Dependent Modification of LDL as a Key Factor of Endothelial Dysfunction and Atherosclerotic Vascular Wall Damage

2022

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“…The protection from the atherosclerosis and the treatment of the disease are complex problems with many unknowns, and so are the modes of action of novel drugs and their metabolism. Many studies concerning probucol and succinobucol have been published [ 13 , 14 , 15 , 20 , 21 , 22 , 23 ]. Starting with these conjugates, a long pathway to discover their real potential is ahead.…”

Section: Introductionmentioning

confidence: 99%

Succinobucol’s New Coat — Conjugation with Steroids to Alter Its Drug Effect and Bioavailability

et al. 2011

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Synthesis, detailed structural characterization (X-ray, NMR, MS, IR, elemental analysis), and studies of toxicity, antioxidant activity and bioavailability of unique potent anti-atherosclerotic succinobucol-steroid conjugates are reported. The conjugates consist of, on one side, the therapeutically important drug succinobucol (4-{2,6-di-tert-butyl-4-[(1-{3-tert-butyl-4-hydroxy-5-(propan-2-yl)phenyl]sulfanyl}ethyl)sulfanyl]phenoxy}-4-oxo-butanoic acid]) possessing an antioxidant and anti-inflammatory activity, and on the other side, plant stanol/sterols (stigmastanol, β-sitosterol and stigmasterol) possessing an ability to lower the blood cholesterol level. A cholesterol-succinobucol prodrug was also prepared in order to enhance the absorption of succinobucol through the intestinal membrane into the organism and to target the drug into the place of lipid metabolism—The enterohepatic circulation system. Their low toxicity towards mice fibroblasts at maximal concentrations, their antioxidant activity, comparable or even higher than that of ascorbic acid as determined by direct quenching of the DPPH radical, and their potential for significantly altering total and LDL cholesterol levels, suggest that these conjugates merit further studies in the treatment of cardiovascular or other related diseases. A brief discussion of succinobucol’s ability to quench the radicals, supported with a computational model of the electrostatic potential mapped on the electron density surface of the drug, is also presented.

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Antioxidants decreases the intensification of low density lipoprotein in vivo peroxidation during therapy with statins

Ланкин¹,

Tikhaze²,

Кухарчук³

et al. 2003

Biochemistry of Diabetes and Atherosclerosis

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Antioxidant probucol as an effective scavenger of lipid radicals in low density lipoproteinsin vivo andin vitro

Cited by 8 publications

References 13 publications

Dicarbonyl-Dependent Modification of LDL as a Key Factor of Endothelial Dysfunction and Atherosclerotic Vascular Wall Damage

Dicarbonyl-Dependent Modification of LDL as a Key Factor of Endothelial Dysfunction and Atherosclerotic Vascular Wall Damage

Succinobucol’s New Coat — Conjugation with Steroids to Alter Its Drug Effect and Bioavailability

Antioxidants decreases the intensification of low density lipoprotein in vivo peroxidation during therapy with statins

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