Effect of Probucol on Antioxidant Properties of HDL in Patients with Heterozygous Familial Hypercholesterolemia

Inagaki, Miwako; Nakagawa-Toyama, Yumiko; Nishida, Makoto; Nakatani, Kazuhiro; Nakaoka, Hajime; Kawase, M.; Kawase, Ryota; Tsubakio-Yamamoto, Kazumi; Masuda, Daisuke; Ohama, Tohru; Matsuyama, Akifumi; Ishigami, Masato; Komuro, Issei; Yamashita, Shizuya

doi:10.5551/jat.12807

Cited by 22 publications

(16 citation statements)

References 41 publications

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“…Probucol inhibited an increase in plasma concentration of HDLC but enhanced the activity of PON-1, an enzyme that protects HDL from oxidation [29], as was found in another study [24], suggesting that the inhibitory effect of probucol on increases in plasma concentration of HDLC did not act as a proatherogenic factor in this animal model.…”

Section: Discussionsupporting

confidence: 76%

“…To measure the antioxidative effect of HDL on reference LDL isolated from the control group, HDL was added to the reference LDL solution (each at a final concentration of protein at 100 µg/mL). The interval between the start of the reaction and the rise in absorbance (the lag time), maximal rate of oxidation, and maximal concentration of CD were calculated as described previously [24] to evaluate the effects of probucol and atorvastatin on LDL-oxidation.…”

Section: Methodsmentioning

confidence: 99%

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Add-On Effect of Probucol in Atherosclerotic, Cholesterol-Fed Rabbits Treated with Atorvastatin

et al. 2014

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ObjectiveLowering the blood concentration of low-density lipoprotein (LDL) cholesterol is the primary strategy employed in treating atherosclerotic disorders; however, most commonly prescribed statins prevent cardiovascular events in just 30% to 40% of treated patients. Therefore, additional treatment is required for patients in whom statins have been ineffective. In this study of atherosclerosis in rabbits, we examined the effect of probucol, a lipid-lowering drug with potent antioxidative effects, added to treatment with atorvastatin.Methods and ResultsAtherosclerosis was induced by feeding rabbits chow containing 0.5% cholesterol for 8 weeks. Probucol 0.1%, atorvastatin 0.001%, and atorvastatin 0.003% were administered solely or in combination for 6 weeks, beginning 2 weeks after the start of atherosclerosis induction. Atorvastatin decreased the plasma concentration of non-high-density lipoprotein cholesterol (non-HDLC) dose-dependently; atorvastatin 0.003% decreased the plasma concentration of non-HDLC by 25% and the area of atherosclerotic lesions by 21%. Probucol decreased the plasma concentration of non-HDLC to the same extent as atorvastatin (i.e., by 22%) and the area of atherosclerotic lesions by 41%. Probucol with 0.003% atorvastatin decreased the plasma concentration of non-HDLC by 38% and the area of atherosclerotic lesions by 61%. Co-administration of probucol with atorvastatin did not affect the antioxidative effects of probucol, which were not evident on treatment with atorvastatin alone, such as prevention of in vitro LDL-oxidation, increase in paraoxonase-1 activity of HDL, and decreases in plasma and plaque levels of oxidized-LDL in vivo.ConclusionsProbucol has significant add-on anti-atherosclerotic effects when combined with atorvastatin treatment; suggesting that this combination might be beneficial for treatment of atherosclerosis.

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Section: Discussionsupporting

confidence: 76%

Section: Methodsmentioning

confidence: 99%

Add-On Effect of Probucol in Atherosclerotic, Cholesterol-Fed Rabbits Treated with Atorvastatin

et al. 2014

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“…The second possible mechanism may be attributed to HDL modulation induced by probucol. It has been reported that HDL functions such as reverse cholesterol transport [6-8] and anti-oxidative activity [18] are markedly up-regulated in probucol-treated patients, while HDL-C levels are low. If these functions occur in the arterial wall, accumulation of lipids would be diminished.…”

Section: Discussionmentioning

confidence: 99%

Probucol inhibits the initiation of atherosclerosis in cholesterol-fed rabbits

et al. 2013

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BackgroundProbucol and statin are often prescribed for treating atherosclerosis. These two drugs exhibit different mechanisms but it is unknown whether they have the same anti-atherogenic properties. In the current study, we examined whether these two drugs at optimal doses could inhibit the initiation of atherosclerosis in cholesterol-fed rabbits in the same way.MethodsNew Zealand White rabbits were fed a cholesterol-rich diet for 5 weeks to produce the early-stage lesions of atherosclerosis. Drug-treated rabbits were administered either probucol or atorvastatin and serum lipids and aortic atherosclerotic lesions were compared with those in a control group.ResultsAtorvastatin treatment significantly reduced serum total cholesterol levels while probucol treatment led to significant reduction of high-density lipoprotein cholesterol levels without changing total cholesterol levels compared with those in the control group. Compared with the control, probucol treatment led to 65% (p < 0.01) reduction while atorvastatin treatment led to 23% (p = 0.426) reduction of the aortic lesion area. Histological and immunohistochemical analyses revealed that the lesions of the probucol-treated group were characterized by remarkable reduction of monocyte adherence to endothelial cells and macrophage accumulation in the intima compared with those of both atorvastatin and control groups. Furthermore, low-density lipoprotein (LDL) isolated from the probucol group exhibited prominent anti-oxidative reaction, which was not present in LDL isolated from either the atorvastatin-treated or the control group.ConclusionsThis study suggests that probucol inhibits the initiation of atherosclerosis by reducing monocyte adherence and infiltration into the subintima. Anti-oxidization of LDL by probucol protects more effectively against early-stage lesion formation than statin-mediated lipid-lowering effects.

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“…Even though probucol has been used in the clinic for many years, there have been no reports of probucol being used to treat spinal cord injuries (Bretzner et al, 2011). Considering the known anti-inflammatory and antioxidant effect of probucol (Inagaki et al, 2012), we sought to evaluate its effect on an animal model of spinal cord injury.…”

Section: Discussionmentioning

confidence: 99%

Protective effect and mechanism of probucol in the treatment of spinal cord injury

Zhu¹,

Wang²,

Sun³

et al. 2015

Genet. Mol. Res.

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ABSTRACT.To investigate the effects of probucol on the treatment of spinal cord injury in rat, 80 rats were randomly divided into two groups of 40: a group treated with probucol and a control group. Allen's method was used to establish a rat model of spinal cord injury. After establishment, probucol (500 mg·kg -1 ·day -1 ) was intraperitoneally injected into the treatment group rats for 1 week, while the same amount of saline was used to treat the control group. On days 1, 7, 14, 21, and 28 after treatment, the function of rats' spinal cord was evaluated according to the Bresnahan locomotor rating scale. Serum protein and mRNA levels of the cytokines [interferon (IFN)-γ, tumor necrosis factor (TNF)-α, and interleukin (IL)-17] were measured using enzyme-linked immunosorbent assay and quantitative polymerase chain reaction, respectively. Protein levels of IFN-γ, TNF-α, IL-17, and the downstream markers signal transducer and activator of transcription (STAT)-1 and STAT-3 were measured using western blot. In addition, the oxidative stress-related parameters, superoxide dismutase (SOD) and malondialdehyde (MDA), were also measured. It was found that compared to control group, rats from the treatment group had significantly lower levels of IFN-γ, TNF-α, and IL-17 (P < 0.05) on days 1 and 7, as well as lower MDA levels and higher SOD activity on days 7, 21, and 28 (P < 0.05). In summary, probucol improved the recovery of locomotion function after spinal cord injury in rats through downregulation of inflammation and upregulation of anti-oxidative activity.

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Effect of Probucol on Antioxidant Properties of HDL in Patients with Heterozygous Familial Hypercholesterolemia

Cited by 22 publications

References 41 publications

Add-On Effect of Probucol in Atherosclerotic, Cholesterol-Fed Rabbits Treated with Atorvastatin

Add-On Effect of Probucol in Atherosclerotic, Cholesterol-Fed Rabbits Treated with Atorvastatin

Probucol inhibits the initiation of atherosclerosis in cholesterol-fed rabbits

Protective effect and mechanism of probucol in the treatment of spinal cord injury

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