Assessment of lipoprotein profiles study (ALPS) and antioxidant activity in healthy subjects treated with AGI-1067

Davidson, Michael; Smith, Joseph Wayne; Scott, Robert C.; Small, Robert J.; Choi, Jasmine; Ishida, Brian Y.; Kane, John P.

doi:10.1016/j.jacl.2007.07.005

Cited by 3 publications

(4 citation statements)

References 30 publications

(29 reference statements)

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“…A multi-center, double-blind, placebo-controlled, 12-week trial showed that AGI-1067 (a phenolic derivative of probucol) had less effect on LDL-C and HDL-C, but significantly increased HDL-related paraoxonase activity and had significant anti-LDL oxidation capacity (reduction of thiobarbituric acid-reactive substances). These results indicate that the anti-atherosclerotic properties of AGI-1067 may be involved in the inhibition of the oxidative-inflammatory cascade rather than the lipid-regulated pathway (Davidson et al, 2007).…”

Section: Probucolmentioning

confidence: 87%

Natural products: The role and mechanism in low‐density lipoprotein oxidation and atherosclerosis

Zhang

Chen

et al. 2020

Phytotherapy Research

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Atherosclerosis is a chronic inflammatory, metabolic, and epigenetic disease, which leads to the life-threatening coronary artery disease. Emerging studies from bench to bedside have demonstrated the pivotal role of low-density lipoprotein (LDL) oxidation in the initiation and progression of atherosclerosis. This article hereby reviews oxidation mechanism of LDL, and the pro-atherogenic and biomarker role of oxidized LDL in atherosclerosis. We also review the pharmacological effects of several representative natural products (vitamin E, resveratrol, quercetin, probucol, tanshinone IIA, epigallocatechin gallate, and Lycopene) in protecting against LDL oxidation and atherosclerosis. Clinical and basic research supports the beneficial effects of these natural products in inhibiting LDL oxidation and preventing atherosclerosis, but the data are still controversial. This may be related to factors such as the population and the dosage and time of taking natural products involved in different studies. Understanding the mechanism of LDL oxidation and effect of oxidized LDL help researchers to find novel therapies against atherosclerosis.

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Section: Probucolmentioning

confidence: 87%

Natural products: The role and mechanism in low‐density lipoprotein oxidation and atherosclerosis

Zhang

Chen

et al. 2020

Phytotherapy Research

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“…In addition, a decrease in very lowdensity lipoprotein cholesterol (-0.47 vs + 0.78 mg/dL, p = 0.022) and a trend towards increased LDL-C (+ 3.02 vs -1.31 mg/dL, p = 0.057) were found with succinobucol treatment. Together with a significant increase in cholesterol ester transfer protein (CETP) mass (+ 0.27 vs -0.04 mg/dL, p < 0.001), these results indicate that succinobucol's effects on the lipid panel may be mediated by increasing the activity of CETP [38].…”

Section: Metabolic and Antiplatelet Effectsmentioning

confidence: 89%

“…It is not associated with increases in weight or waist circumference [37]. However, data show consistently unfavorable changes to the lipid profile with succinobucol treatment, including statistically significant decreases in HDL-C [34,35,37,38]. In addition, data from ARISE show significant increases in both systolic (+ 1.7 mmHg) and diastolic (+ 0.5 mmHg) blood pressure with succinobucol treatment compared with placebo [37].…”

Section: Safety and Tolerabilitymentioning

confidence: 98%

“…In CART-2, LDL-C increased by 4% with succinobucol 280 mg daily compared with a 9% reduction with placebo (p < 0.05) [35]. The effect of succinobucol on lipid parameters was specifically studied in 154 healthy subjects in the Assessment of Lipoprotein Profiles Study (ALPS) [38]. Succinobucol 300 mg daily was found to significantly decrease HDL-C (-3.95 vs -0.53 mg/dL, p < 0.001) compared with placebo after 3 months of therapy.…”

Section: Metabolic and Antiplatelet Effectsmentioning

confidence: 99%

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Succinobucol: review of the metabolic, antiplatelet and cardiovascular effects

Muldrew

Franks

2009

Expert Opinion on Investigational Drugs

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Background: Succinobucol (AGI-1067) was developed as a probucol derivative with anti-inflammatory and antioxidant properties. It has undergone Phase III clinical trials to determine its place in the treatment of atherosclerotic disease. Objective: This paper reviews the available history, pharmacology and preclinical and clinical trial data of succinobucol. Methods: Data were compiled following review of publications indexed in Medline and International Pharmaceutical Abstracts, industry media releases and relevant bibliographies. Results/conclusion: In preclinical studies, succinobucol exhibited antioxidant, anti-inflammatory, antihyperglycemic and antiplatelet properties; however, these effects have not resulted in a reduction in cardiovascular clinical end points in clinical trials. Although proposed antihyperglycemic effects are being investigated, safety concerns and lack of clear cardiovascular benefit may limit its clinical use as an antihyperglycemic agent.

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Antioxidants in the Fight Against Atherosclerosis: Is This a Dead End?

Toledo-Ibelles

Mas‐Oliva

2018

Curr Atheroscler Rep

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Purpose of ReviewThe purpose of this review is to focus on the outcome of recent antioxidant interventions using synthetic and naturally occurring molecules established as adjuvant strategies to lipid-lowering or anti-inflammatory therapies designed to reduce the risk of cardiovascular disease.Recent FindingsTo date, accumulated evidence regarding oxidation as a pro-atherogenic factor indicates that redox biochemical events involved in atherogenesis are indeed a very attractive target for the management of cardiovascular disease in the clinic. Nevertheless, although evidence indicates that redox reactions are important in the initiation and progression of atherosclerosis, oxidation with a pro-atherogenic context does not eliminate the fact that oxidation participates in many cases as an essential messenger of important cellular signaling pathways. Therefore, disease management and therapeutic goals require not only high-precision and high-sensitivity methods to detect in plasma very low amounts of reducing and oxidizing molecules but also a much better understanding of the normal processes and metabolic pathways influenced and/or controlled by oxidative stress. As several methodologies have been specifically described for the quantification of the total antioxidant capacity and the oxidation state of diverse biological systems, a successful way to carefully study how redox reactions influence atherosclerosis can be achieved.SummarySince there is still a lack of standardization with many of these methods, clinical trials studying antioxidant capacity have been difficult to compare and therefore difficult to use in order to reach a conclusion. We believe a comprehensive analysis of new knowledge and its relationship with the presence of plasma antioxidants and their reducing capacity will undoubtedly open new ways to understand and develop new therapeutic pathways in the fight not only against atherosclerosis but also against other degenerative diseases.

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Assessment of lipoprotein profiles study (ALPS) and antioxidant activity in healthy subjects treated with AGI-1067

Cited by 3 publications

References 30 publications

Natural products: The role and mechanism in low‐density lipoprotein oxidation and atherosclerosis

Natural products: The role and mechanism in low‐density lipoprotein oxidation and atherosclerosis

Succinobucol: review of the metabolic, antiplatelet and cardiovascular effects

Antioxidants in the Fight Against Atherosclerosis: Is This a Dead End?

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