Hypocholesterolesmic Effect of 4,4′-(Isopropylidenedithio)-Bis(2,6-di-t-Butylphenol) (Probucol)

Barnhart, James W.; Sefranka, J. A.; Mcintosh, David D.

doi:10.1093/ajcn/23.9.1229

Cited by 108 publications

(42 citation statements)

References 9 publications

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“…Probucol is a bisphenol compound that was synthesized as an anti-oxidant and found to have the potential to reduce cholesterol [10,11] . Probucol is an anti-oxidant and lipid-reducing drug that has been in clinical use during the past few decades for the prevention and treatment of cardiovascular diseases.…”

Section: Original Articlementioning

confidence: 99%

Probucol inhibits LPS-induced microglia activation and ameliorates brain ischemic injury in normal and hyperlipidemic mice

et al. 2016

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Aim: Increasing evidence suggests that probucol, a lipid-lowering agent with anti-oxidant activities, may be useful for the treatment of ischemic stroke with hyperlipidemia via reduction in cholesterol and neuroinflammation. In this study we examined whether probucol could protect against brain ischemic injury via anti-neuroinflammatory action in normal and hyperlipidemic mice. Methods: Primary mouse microglia and murine BV2 microglia were exposed to lipopolysaccharide (LPS) for 3 h, and the release NO, PGE2, IL-1β and IL-6, as well as the changes in NF-κB, MAPK and AP-1 signaling pathways were assessed. ApoE KO mice were fed a high-fat diet containing 0.004%, 0.02%, 0.1% (wt/wt) probucol for 10 weeks, whereas normal C57BL/6J mice received probucol (3, 10, 30 mg·kg -1 ·d -1 , po) for 4 d. Then all the mice were subjected to focal cerebral ischemia through middle cerebral artery occlusion (MCAO). The neurological deficits were scored 24 h after the surgery, and then brains were removed for measuring the cerebral infarct size and the production of pro-inflammatory mediators. Results: In LPS-treated BV2 cells and primary microglial cells, pretreatment with probucol (1, 5, 10 μmol/L) dose-dependently inhibited the release of NO, PGE2, IL-1β and IL-6, which occurred at the transcription levels. Furthermore, the inhibitory actions of probucol were associated with the downregulation of the NF-κB, MAPK and AP-1 signaling pathways. In the normal mice with MCAO, preadministration of probucol dose-dependently decreased the infarct volume and improved neurological function. These effects were accompanied by the decreased production of pro-inflammatory mediators (iNOS, COX-2, IL-1, IL-6). In ApoE KO mice fed a high-fat diet, pre-administration of 0.1% probucol significantly reduced the infarct volume, improved the neurological deficits following MCAO, and decreased the total-and LDL-cholesterol levels. Conclusion: Probucol inhibits LPS-induced microglia activation and ameliorates cerebral ischemic injury in normal and hyperlipidemic mice via its anti-neuroinflammatory actions, suggesting that probucol has potential for the treatment of patients with or at risk for ischemic stroke and hyperlipidemia.

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Section: Original Articlementioning

confidence: 99%

Probucol inhibits LPS-induced microglia activation and ameliorates brain ischemic injury in normal and hyperlipidemic mice

et al. 2016

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“…Consistent with this possibility are earlier studies that showed that (a) other apolipoproteins found in HDL (e.g., apoA-II) can serve as ligands for SR-BI (28); and (b) adenovirus-mediated overexpression of SR-BI in apoA-I KO mice results in the loss of virtually all of the apoA-I-deficient HDL cholesterol (K. Kozarsky and M. Donahee, personal communication). There was a reduction in the amount of HDL-like cholesterol in the SR-BI/apoA-I double -KO relative to SR-BI KO (Figure 1a, open circles) mice, with the greatest reduction seen in the smallest, normal-sized HDL particles (fractions [29][30][31][32][33][34][35][36][37][38]. Therefore, in the context of a SR-BI KO background, the loss of apoA-I resulted in significant changes in the structure of the HDL (e.g., no apoA-I, altered size distribution) and the amount of HDL cholesterol.…”

Section: Figurementioning

confidence: 99%

Abnormal lipoprotein metabolism and reversible female infertility in HDL receptor (SR-BI)–deficient mice

Miettinen¹,

Rayburn²,

Krieger³

2001

J. Clin. Invest.

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“…10 Antioxidants may attenuate atherosclerosis because they inhibit lipid hydroperoxide formation and hence, lipoprotein oxidation. 1 Probucol, a lipid-lowering antioxidant, 11 has been extensively studied in experimental intervention studies of atherosclerosis. Its overall effects, however, remain somewhat contentious.…”

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confidence: 99%

Site-Specific Antiatherogenic Effect of Probucol in Apolipoprotein E–Deficient Mice

Witting

Pettersson

Letters

et al. 2000

ATVB

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Abstract-The lipid-lowering antioxidant probucol can inhibit atherosclerosis in animals and restenosis in humans.However, probucol has been shown to promote atherosclerosis in the aortic root of apolipoprotein E-deficient (apoEϪ/Ϫ) mice. In the current study, we examined the effects of probucol on both lesion formation at 4 sites along the aorta and lipoprotein oxidation in the plasma and aortas of apoEϪ/Ϫ mice receiving a diet containing 21.2% (wt/wt) fat and 0.15% (wt/wt) cholesterol without or with 1% (wt/wt) probucol. After 6 months, controls had developed lesions at all sites investigated. Lesion development was strongly (Pϭ0.0001) affected by probucol, but this effect was not uniform: lesion size was increased in the aortic root but significantly decreased in the arch, the descending thoracic aorta, and proximal abdominal aorta. Plasma and aortas of probucol-treated mice contained high concentrations of probucol and its metabolites (bisphenol and diphenoquinone); increased vitamin C; markedly decreased very low density lipoprotein (but not low density lipoprotein and high density lipoprotein); and decreased cholesterol, cholesteryl esters, triglycerides, vitamin E, and oxidized lipids compared with controls. Interestingly, probucol treatment did not decrease the proportion of aortic lipids that were oxidized. Plasma vitamin C and bisphenol, but not probucol, protected plasma lipids from ex vivo oxidation by peroxyl radicals. These results show that as in other species, probucol can inhibit lesion formation in most parts of the aorta of apoEϪ/Ϫ mice. This effect may involve lipid oxidation-independent mechanisms localized within the vessel wall as well as lipid lowering.

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Hypocholesterolesmic Effect of 4,4′-(Isopropylidenedithio)-Bis(2,6-di-t-Butylphenol) (Probucol)

Cited by 108 publications

References 9 publications

Probucol inhibits LPS-induced microglia activation and ameliorates brain ischemic injury in normal and hyperlipidemic mice

Probucol inhibits LPS-induced microglia activation and ameliorates brain ischemic injury in normal and hyperlipidemic mice

Abnormal lipoprotein metabolism and reversible female infertility in HDL receptor (SR-BI)–deficient mice

Site-Specific Antiatherogenic Effect of Probucol in Apolipoprotein E–Deficient Mice

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