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Atherosclerosis
Published in George Feuer, Felix A. de la Iglesia, Molecular Biochemistry of Human Disease, 2020
George Feuer, Felix A. de la Iglesia
One of the most widely studied compounds is triparanol (4-chloro-α-[4-[2-〈diethylamino〉ethoxy]phenyl]-〈4-methylphenyl〉benzeneethanol, MER-29).17,71,192 Triparanol lowers blood cholesterol by inhibiting 75% or more of the endogenous synthesis. It blocks the reduction of the 24, 25 double bond in the steroid side chain, leading to the accumulation of 25-dehydrocholesterol, as it is commonly known, desmosterol.627 Desmosterol replaces cholesterol in lipoproteins, and therefore, triparanol therapy leads to the accumulation of the precursor compound in the blood in place of cholesterol. The lipoprotein pattern returns to normal in Type II patients but not in Type IV. Probucol has no consistent action on lipogenesis in experiments, but apparently decreases endogenous cholesterol synthesis and intestinal reabsorption.
Micronutrients for Improved Management of Huntington’s Disease
Published in Kedar N. Prasad, Micronutrients in Health and Disease, 2019
Probucol is known to exhibit antioxidant activity. Treatment with probucol prevented ROS formation and lipid peroxidation in all chemical-induced HD models (quinolinic acid; as an excitotoxic model, 3-NP; as an inhibitor of mitochondrial succinate dehydrogenase model, and combined model of quinolinic acid and 3-NP treatment), but it did not protect against 3-NP-induced mitochondrial dysfunctions.118 Treatment with sodium succinate protected striatal slices only against 3-NP-induced mitochondrial dysfunctions. Treatment with a NMDA receptor antagonist MK-801 (also called Dizocilpine) protected mitochondrial dysfunctions in all HD models used in this study. These data suggest that a combination of NMDA receptor antigonist and an antioxidants may be more useful in reducing oxidatve stress and mitochondrial dysfunction than the individual agents.
Oxidants and Antioxidants
Published in P. K. Shah, Risk Factors in Coronary Artery Disease, 2006
Antioxidants have also been tested for a potential therapeutic role in the reduction of restenosis after angioplasty. In the Multivitamin and Probucol study, the effect of a combination of vitamins (1 g of vitamin C, 1,400 IU of vitamin E and 100 mg of beta-carotene) and probucol given separately or together on the rate of restenosis after angioplasty was investigated (25). Probucol was found to significantly reduce restenosis, whereas antioxidant vitamins were without effect. Also the Probucol Angioplasty Restenosis Trial reported a significant reduction in restenosis in response to probucol treatment (26).
Understanding the role of chronopharmacology for drug optimization: what do we know?
Published in Expert Review of Clinical Pharmacology, 2023
Akio Fujimura, Kentaro Ushijima
Rev-Erbα is also involved in circadian variation in the activity of cholesterol 7α-hydroxylase in the liver, which is reflected in the rate of conversion of cholesterol to bile acid [58]. Probucol increases the activity of hepatic cholesterol 7α-hydroxylase and conversion of cholesterol to bile acid, which in turn decreases the cholesterol concentration in blood [61]. It has been clearly demonstrated that the cholesterol-lowering effect of probucol is greater after repeated dosing at night (19:00) than in the morning (7:00) in patients with elevated cholesterol [62]. Given that the activity of hepatic cholesterol 7α-hydroxylase exhibits a trough during a rest period [63], the probucol-induced increment in enzyme activity is potentially larger after dosing at night than after dosing in the morning, which might represent a beneficial effect of chronotherapy when administering probucol.
Efficacy and safety of add on therapies in patients with hypercholesterolemia undergoing statin therapy
Published in Expert Opinion on Pharmacotherapy, 2020
Brian Tomlinson, Paul Chan, Yuzhen Zhang, Christopher Wai Kei Lam
Some lipid-modifying treatments have very limited indications and others have been withdrawn or have restricted availability and these will not be included in this review. Lomitapide and mipomersen have been used for the very rare condition of homozygous familial hypercholesterolemia (HoFH). These drugs are quite effective in lowering LDL-C but they have considerable safety issues [14]. Probucol was withdrawn in western countries but is still used in Japan and some other Asian countries in high-risk patients such as those with severe familial hypercholesterolemia (FH) [15]. It reduces high-density lipoprotein cholesterol (HDL-C), which was thought to be a disadvantage, but it may actually improve HDL function, and it did show a benefit in a recent trial in Asian patients with ischemic stroke [16].
Novel nano-encapsulation of probucol in microgels: scanning electron micrograph characterizations, buoyancy profiling, and antioxidant assay analyses
Published in Artificial Cells, Nanomedicine, and Biotechnology, 2018
Armin Mooranian, Nassim Zamani, Momir Mikov, Svetlana Goločorbin-Kon, Goran Stojanovic, Frank Arfuso, Hani Al-Salami
Probucol (PB) is a medication prescribed for hypercholesterolemia. It possesses desirable antidiabetic effects such as antioxidant and β-cell protective effects [7]. PB is highly hydrophobic and has poor bioavailability and significant inter- and intra-patient absorption, which limits its potential clinical applications in DM. Recent studies in our laboratory have shown potential use of PB and various bile acids in diabetes; however, conventional PB release matrices remain inadequate and its release remains variable after oral administration [7–10]. To optimize its targeted release properties and enhance its gut absorption, PB needs to be encapsulated with a new polymer (with controlled release properties), and with an absorption enhancer. Eudragit® (ED) polymers have been recently examined in drug delivery and have shown to optimize the physical properties of many drug-delivery systems and matrices [11], whereas the bile acid chenodeoxycholic acid (CDCA) has been shown to possess absorption-enhancing properties [12]. ED polymers are composed of poly (methyl) acrylate polymer systems with unique physicochemical properties that enable them to have high flexibility, low permeability and pH-dependant swelling properties allowing for their wide range applications in pharmaceutical formulations. Both ED and CDCA need to be encapsulated and formulated with PB to form a single delivery matrix capable of targeted-oral delivery of PB into the lower part of the gut, where it is maximally absorbed.