Protection of cardiac membrane phospholipid against oxidative injury by calcium antagonists

Janero, David R.; Burghardt, Barbara; López, Rocío Gloria Fernández

doi:10.1016/0006-2952(88)90116-5

Cited by 77 publications

(21 citation statements)

References 39 publications

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“…The antioxidant activity of this calcium antagonist is therefore connected to a radicaltrapping eect. A samewhat similar mechanism of action has already been suggested for other calcium antagonists (Janero et al, 1988;Engineer & Sridhar, 1989;Ondrias et al, 1989;Goncalves et al, 1991). The relationship between the free radical scavenging properties of these drugs and their chemical structure has been analysed.…”

Section: Discussionsupporting

confidence: 53%

“…Some blockers of b-adrenoceptors and calcium antagonists (especially of the dihydropyridine type) have been recently shown to inhibit membrane lipid peroxidation initiated by free radical generating systems (Janero & Burghardt, 1989;Janero et al, 1988;Mak & Weglicki, 1990;Mak et al, 1988;Van Amsterdam et al, 1992;Yue et al, 1992). It has also been observed that nicardipine (but not nifedipine) has a direct protective eect on rat single, cardiac myocytes exposed to reoxygenation injury (Hano et al, 1991).…”

Section: Introductionmentioning

confidence: 99%

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Protective effect of darodipine, a calcium antagonist, on rat cardiomyocytes against oxygen radical‐mediated injury

Matucci

Ottaviani

Barbieri

et al. 1997

British J Pharmacology

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1 We used electrophysiological and electron spin resonance (e.s.r.) techniques to study the mechanism of the protective eect of darodipine on rat isolated cardiomyocytes exposed to an exogenous source of oxygen free radicals (OFR). 2 The L-type calcium current (I Ca,L ), action potential and cell shortening were measured in patchclamped cells in the whole-cell con®guration. I Ca,L blockade by darodipine was concentration-dependent, peak current being reduced by 20% with 50 nM and by 58% with 100 nM darodipine. The lowest concentration of darodipine did not aect action potential or twitch pro®le. 3 Exposure to OFR-generating solution (5 mM dihydroxyfumarate, DHF) caused the appearance of electrophysiological alterations and/or spontaneous activity in 73% of cells (n=26) within 5 min; action potential duration (APD) was prolonged (195+16 ms vs 140+6 ms in the control) and maximum diastolic potential (MDP) was reduced (759.5+2.6 mV vs 769.8+0.8 mV in the control) (P50.05, n=25). 4 A 2 min pretreatment with 50 nM darodipine signi®cantly reduced the incidence of these arrhythmogenic events following a 5 min exposure to OFR (36% of cells, n=14; P50.05 vs nonpretreated cells). Pretreatment with darodipine also prevented APD prolongation caused by OFR (137+12 ms after DHF vs 117+6 ms before DHF n=14, not signi®cant) but not the decrease of MDP (763.4+2.5 mV after DHF vs 770.9+1.0 mV before DHF, P50.05). 5 The e.s.r. spectra obtained from the DHF-DMPO solution in the absence of darodipine demonstrated the presence of two components corresponding to two DMPO adducts. The addition of darodipine (50 ± 500 nM) led to a concentration-dependent decrease in intensity of the signals, the intensity of the DMPO-COO .7 adduct being decreased more than that of the DMPO-OH . adduct.6 Our results demonstrate that darodipine dose-depentently blocks I Ca,L in rat isolated cardiomyocytes. Furthermore it exerts protective eects against free-radical-induced electrophysiological alterations independently of its calcium antagonistic properties; this eect is possibly due to trapping of speci®c radical species.

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Section: Discussionsupporting

confidence: 53%

Section: Introductionmentioning

confidence: 99%

Protective effect of darodipine, a calcium antagonist, on rat cardiomyocytes against oxygen radical‐mediated injury

Matucci

Ottaviani

Barbieri

et al. 1997

British J Pharmacology

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“…While di-t-BHA, NDGA, BHT and di-BHA were the most potent, nifedipine and caffeic acid were the least effective scavengers of peroxyl radicals. Though the antiperoxidant action of nifedipine, described elsewhere (Janero et al, 1988;Janero & Burghardt, 1989), is difficult to interpret because it was used only at stronger concentrations than those required for effective calcium antagonism, caffeic acid might be of more than theoretical interest as an antioxidizing agent. In mammals, in fact, caffeic acid might be found in sufficient concentrations as a metabolite of chlorogenic and neochlorogenic acid, abundant components of many foodstuffs, to be a reliable and readily forming antioxidant resource, though devoid of spasmolytic activity.…”

Section: Discussionmentioning

confidence: 99%

Calcium antagonist and antiperoxidant properties of some hindered phenols

Sgaragli

Valoti

Gorelli

et al. 1993

British J Pharmacology

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1 The calcium antagonist and antioxidant activities of certain synthetic and natural phenols, related to BHA (2-t-butyl-4-methoxyphenol), were evaluated in rat ileal longitudinal muscle and in lipid peroxidation models respectively. 2 Compounds with a phenol or a phenol derivative moiety, with the exception of 2,2'-dihydroxy-3,-3'-di-t-butyl-5,5'-dimethoxydiphenyl (di-BHA), inhibited in a concentration-dependent manner the BaCl2-induced contraction of muscle incubated in a Ca2+-free medium. Calculated pIC50 (M) values ranged between 3.32 (probucol) and 4.96 [3,5-di-t-butyl-4-hydroxyanisole (di-t-BHA)], with intermediate activity shown by khellin

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“…Third, 13 (76%) of the present patients were being treated with angiotensin-converting enzyme inhibitors and/or calcium channel antagonists, which could affect the concentration of MDA-LDL. 33,34 However, these treatments were started at least 3 months prior to registration, and their dosages were not changed within 3 months of registration or during the study. Therefore, we do not believe that these drugs strongly affected our results.…”

Section: Study Limitationsmentioning

confidence: 99%

Effects of Atorvastatin and Pravastatin on Malondialdehyde-Modified LDL in Hypercholesterolemic Patients

Tamura

Watanabe

Nasu

2003

Circ J

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xidized low-density lipoprotein (LDL) plays a key role in the initiation and development of atherosclerosis through a variety of effects, such as recruitment of monocytes, adhesion of leukocytes to endothelial cells, promotion of intraluminal thrombosis, activation of lymphocytes, enhanced cytotoxicity, and impairment of endothelium-dependent vasorelaxation. [1][2][3][4] It has become possible to measure the serum concentrations of oxidized LDL or malondialdehyde-modified LDL (MDA-LDL) 5-11 and their circulating concentrations have been reported to be significantly higher in patients with coronary artery disease (CAD) than in controls. 9-11 Sasaki et al reported that atorvastatin decreased the serum concentration of MDA-LDL in patients with mixed hyperlipoproteinemia 12 and although atorvastatin produces greater reductions in the serum concentrations of total and LDL cholesterol than other statins, such as simvastatin, pravastatin, lovastatin, and fluvastatin, 13 it is unclear whether this statin has more effect on decreasing the serum concentrations of MDA-LDL than other statins. In the present study, we compared the effects of atorvastatin and pravastatin on the serum concentrations of MDA-LDL in hypercholesterolemic patients. Methods Study PopulationThe study patients consisted of 17 patients (10 men, 7women; mean age, 68±9 years) who were indicated for drug therapy based on the National Cholesterol Education Program II. 14 Exclusion criteria were: (1) use of anti-inflammatory or lipid-lowering drugs or antioxidant supplements, (2) currently smoking, (3) renal or liver dysfunction, (4) diabetes mellitus, (5) the presence of angina attacks, (6) a history of stroke or acute coronary syndrome within 6 months, (7) a history of coronary interventional therapy within the past year, (8) chronic heart failure, (9) collagen disease, infection, malignant diseases, or recent (<6 months) major surgery or trauma, and (10) change in the drugs administered within the 3 months prior to registration in the study. Study ProtocolThe study protocol is shown in Fig 1. It was a randomized crossover design and the study started 1 month after registration. The patients underwent an 8-week regimen of statin therapy of either atorvastatin (10 mg/day) or pravastatin (10 mg/day) with a 4-week washout period between drugs. The study protocol was in agreement with the guidelines of the institutional ethics committee and informed consent was obtained from each patient prior to enrollment in the study.After an overnight fast, venous blood samples were obtained before and after the 8-week treatment with atorvastatin or pravastatin. The concentrations of LDL cholesterol, triglycerides, and HDL cholesterol were assayed by enzymatic methods. Serum concentrations of MDA-LDL were measured using an enzyme immunoassay kit (SRL, Inc, Tokyo, Japan). Intra-and inter-assay variations were within 3.5% and 6.9%, respectively. Statistical AnalysisAll data are expressed as means ± SD. Paired t test was Effects of Atorvastatin and Pravastatin on Malondiald...

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Protection of cardiac membrane phospholipid against oxidative injury by calcium antagonists

Cited by 77 publications

References 39 publications

Protective effect of darodipine, a calcium antagonist, on rat cardiomyocytes against oxygen radical‐mediated injury

Protective effect of darodipine, a calcium antagonist, on rat cardiomyocytes against oxygen radical‐mediated injury

Calcium antagonist and antiperoxidant properties of some hindered phenols

Effects of Atorvastatin and Pravastatin on Malondialdehyde-Modified LDL in Hypercholesterolemic Patients

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