Probucol treatment attenuates the aortic atherosclerosis in Watanabe heritable hyperlipidemic rabbits

Oshima, Reiko; Ikeda, Toshiko; Watanabe, Kazuo; Itakura, Hiroshige; Sugiyama, Nobutoshi

doi:10.1016/s0021-9150(97)00243-8

Cited by 25 publications

(8 citation statements)

References 29 publications

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“…Others have suggested that in rabbits, probucol may be antiatherogenic by increasing the activity of CE transfer protein. 40 Although we did not measure this activity, blood parameters alone are not likely to explain the site-specific proatherogenic or antiatherogenic effect of probucol, as all sites are exposed to the same blood.…”

Section: Discussionmentioning

confidence: 96%

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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Section: Discussionmentioning

confidence: 96%

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

Witting

Pettersson

Letters

et al. 2000

ATVB

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“…However effective it is at reversing established atherosclerosis, is yet to be determined. The recent article by Oshima et al [36] suggests that probucol showed evidence for parietal reversal or changes in the pathology of established atherosclerosis in WHHL rabbits in a direction that is consistent with some reversal of the process. It is one thing to show that a drug can slow the progression of a disease, but it is something else to show that it can promote reversal of the disease.…”

Section: The Effect Of Probucol On Xanthoma Regressionmentioning

confidence: 94%

“…How effective it is at reversing established atherosclerosis, is yet to be determined. A recent article by Oshima et al [36] showed that probucol treatment attenuated aortic atherosclerosis in Watanabe heritable hyperlipidemic rabbits. To show that a drug can slow the progression of a disease is one thing, but it is something else to show that it can promote reversal of the disease.…”

Section: Effect On Xanthoma Regressionmentioning

confidence: 99%

Probucol

Pfuetze

Dujovne

2000

Curr Atheroscler Rep

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The purpose of this review article is twofold. It seeks to present an overview of research studies conducted on the many effects of probucol, and it demonstrates the interest in pursuing studies on probucol"s multiple specific actions and its future as a therapeutic agent. Within this article, the results of animal studies, experimental human studies, and clinical human studies are detailed, as is information on toxicology studies and on the side effects of the drug.

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“…Antioxidative activities of components of Rhubarb were shown in Table 3 compared with probucol, a representative antioxidant that has been reported to prevent the progression of atherosclerotic lesions (Nagano et al, 1992;Oshima et al, 1998;Braesen et al, 1995). Antioxidative activities were found in seven of 18 Rhubarb components.…”

Section: Antioxidative Activities Of Components Of Rhubarbmentioning

confidence: 99%

Evaluation of Rhubarb using antioxidative activity as an index of pharmacological usefulness

Iizuka

Iijima

Kondo

et al. 2004

Journal of Ethnopharmacology

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Probucol treatment attenuates the aortic atherosclerosis in Watanabe heritable hyperlipidemic rabbits

Cited by 25 publications

References 29 publications

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

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

Probucol

Evaluation of Rhubarb using antioxidative activity as an index of pharmacological usefulness

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