Antioxidant Dihydropyridines, A New and Comprehensive Therapy for Free Radical-Induced Cardiovascular Diseases

Gaviraghi, G.; Pastorino, Antonio M.; Ratti, Emiliangelo; Trist, D.G.

doi:10.1007/978-94-017-1607-9_15

Cited by 3 publications

(5 citation statements)

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“…The hyperlipemic hamster model has been used to examine the effects of drugs (Nicolosi, 1991) and diet (Kahlon et al, 1992) on lipids and the development of atherosclerosis. The hamster is an excellent model as it has an omnivorous diet, its hepatic cholesterol synthesis is like that in humans, and it has a significant proportion of LDL in the plasma and develops atheromas in a human-like progression (Gaviraghi et al, 1997). We tested CE+AA because it had several components known to beneficially affect lipids in animals, namely, ascorbic acid and flavonoids.…”

Section: Discussionmentioning

confidence: 99%

A Citrus Extract plus Ascorbic Acid Decreases Lipids, Lipid Peroxides, Lipoprotein Oxidative Susceptibility, and Atherosclerosis in Hypercholesterolemic Hamsters

Vinson

Jung

et al. 1998

J. Agric. Food Chem.

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A citrus extract containing flavonoids and ascorbic acid was used as a supplement to investigate its effect on lipids in hypercholesterolemic hamsters. Ascorbic acid or the flavonoids were without effect except that ascorbate did significantly raise HDL. After 1 month of feeding, the citrus extract plus ascorbic acid synergistically caused a significant reduction of 77%, 66%, and 40% in plasma total cholesterol, LDL + VLDL, and triglycerides, respectively, in comparison to the control group. The extract was also a synergistic inhibitor of in vitro cupric ion LDL + VLDL oxidation compared with ascorbic acid or the flavonoids alone. In a second 10-week hamster study, citrus extract plus ascorbate also significantly lowered plasma lipids, lipid peroxides, and ex vivo LDL + VLDL oxidizability vs a control group. Citrus extract plus ascorbate strongly inhibited atherosclerosis, and there was a significant correlation between several indices of oxidative susceptibility and atherosclerosis. Keywords: Lipids; atherosclerosis; flavonoids; lipid peroxidation; hamster

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Section: Discussionmentioning

confidence: 99%

A Citrus Extract plus Ascorbic Acid Decreases Lipids, Lipid Peroxides, Lipoprotein Oxidative Susceptibility, and Atherosclerosis in Hypercholesterolemic Hamsters

Vinson

Jung

et al. 1998

J. Agric. Food Chem.

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“…However, majority of data obtained on various animal cells and tissues by other authors show the protective role of DHPs against both LP and oxidative stress [ 113 , 163 , 164 ].…”

Section: 14-dihydropyridines: a Separate Group Of Bioantioxidantsmentioning

confidence: 99%

“…Dubur et al [ 89 ] observed overwhelming steric influence of substituents in position 4 of the DHP ring. Gaviraghi et al [ 163 , 164 ] proposed that AO activity of DHPs is partly dependent on capacity of the 1,4-DHP ring to donate electrons to the propagating radical (ROO • or RO • ) and to reduce it to a less reactive form. The abstraction (donation) of electron and/or H in the oxidation and LP reactions takes place from all 3,5-dicarbonyl-1,4-DHP systems and results in the formation of corresponding pyridine derivatives (Augustyniak et al [ 51 ]).…”

Section: 14-dihydropyridines: a Separate Group Of Bioantioxidantsmentioning

confidence: 99%

“…It was observed that nicardipine preferentially targets RO • radicals and is inactive against ROO • . Lacidipine, on the other hand, is equally active towards both types of radicals (Gaviraghi et al [ 164 ]). The cytoprotective effect against exposure to H 2 O 2 was more significant for lacidipine (ID 50 = 14 nM, its log⁡ P = 5.4, membrane partition = 136000, assumes position located 7 Å near to the membrane center; other less lipophilic DHPs located 12–16 Å far from the center) as compared to amlodipine, nifedipine, and nicardipine, in smooth muscle cell culture (Gaviraghi et al [ 164 ]).…”

Section: 14-dihydropyridines: a Separate Group Of Bioantioxidantsmentioning

confidence: 99%

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1,4‐Dihydropyridine Derivatives: Dihydronicotinamide Analogues—Model Compounds Targeting Oxidative Stress

Velēna

Žarković

Trošelj

et al. 2016

Oxidative Medicine and Cellular Longevity

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Many 1,4-dihydropyridines (DHPs) possess redox properties. In this review DHPs are surveyed as protectors against oxidative stress (OS) and related disorders, considering the DHPs as specific group of potential antioxidants with bioprotective capacities. They have several peculiarities related to antioxidant activity (AOA). Several commercially available calcium antagonist, 1,4-DHP drugs, their metabolites, and calcium agonists were shown to express AOA. Synthesis, hydrogen donor properties, AOA, and methods and approaches used to reveal biological activities of various groups of 1,4-DHPs are presented. Examples of DHPs antioxidant activities and protective effects of DHPs against OS induced damage in low density lipoproteins (LDL), mitochondria, microsomes, isolated cells, and cell cultures are highlighted. Comparison of the AOA of different DHPs and other antioxidants is also given. According to the data presented, the DHPs might be considered as bellwether among synthetic compounds targeting OS and potential pharmacological model compounds targeting oxidative stress important for medicinal chemistry.

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“…DHPs act as chain-breaking antioxidants, probably because the dihydropyridine ring can lose two electrons and a proton to become the corresponding aromatic pyridine. Oxidation is known to increase plaque formation by stimulating the formation of foam cells and possibly by activating transcription factors known to be involved in transducing growth factors that may contribute to the progression of plaque [7]. Thus, not all CEBs may be as effective as others and this has been seen in a number of animal models of atherosclerosis [2].…”

mentioning

confidence: 99%

Calcium antagonists as anti-atherosclerotic agents

Gaviraghi¹,

Trist²

1998

Emerging Drugs

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Hypercholesterolaemia and hypertension are two major risk factors for atherosclerosis. Each contributes to the progression of plaque, which can eventually occlude arteries leading to myocardial infarction (MI), stroke and peripheral vascular damage. Both elevated blood pressure and high plasma cholesterol can now be controlled with anti-hypertensives and medicines such as 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors, or statins, but no treatments are available that act specifically to reduce or reverse the progression of plaque. Calcium entry blockers (CEBs) are potent anti-hypertensives. However, the rationale for the use of a CEB to interfere with the mechanisms of plaque formation is also strong. It can be hypothesised that CEBs should potentially be able to reduce cholesterol deposition, cellular proliferation and migration and increased cellular matrix, since all of these processes involve calcium. However, CEBs are a heterogeneous class, differing in terms of structure, potency, vascular selectivity and duration of action. In addition, some possess additional properties such as anti-oxidant activity. The newer, third generation dihydropyridines, such as lacidipine, which combine potent CEB activity with long duration of action and anti-oxidant activity, offer the best hope of demonstrating anti-atherosclerotic effects in man. Animal data have confirmed that CEBs are able to reduce plaque progression, though to differing extents. Few so far have been assessed in man. Of those tested, results have not been encouraging. However, the ongoing trials with longer-acting compounds, such as lacidipine (ELSA), are of longer duration and are using B-mode ultrasonography monitoring to afford more precise measurements of atherosclerotic plaque progression. Thus, more consistent daily cover by the CEB should be expected, and the longer monitoring period and the more sensitive measurement should afford an improved chance of demonstrating clinical efficacy.

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Antioxidant Dihydropyridines, A New and Comprehensive Therapy for Free Radical-Induced Cardiovascular Diseases

Cited by 3 publications

References 74 publications

A Citrus Extract plus Ascorbic Acid Decreases Lipids, Lipid Peroxides, Lipoprotein Oxidative Susceptibility, and Atherosclerosis in Hypercholesterolemic Hamsters

A Citrus Extract plus Ascorbic Acid Decreases Lipids, Lipid Peroxides, Lipoprotein Oxidative Susceptibility, and Atherosclerosis in Hypercholesterolemic Hamsters

1,4‐Dihydropyridine Derivatives: Dihydronicotinamide Analogues—Model Compounds Targeting Oxidative Stress

Calcium antagonists as anti-atherosclerotic agents

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