Antioxidant properties of calcium antagonists related to membrane biophysical interactions

Mason, R. Preston; Mak, I. Tong; Trumbore, Mark W.; Mason, Pamela E.

doi:10.1016/s0002-9149(99)00360-4

Cited by 105 publications

(54 citation statements)

References 20 publications

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“…36,37 Furthermore, amlodipine has been found to have potent antioxidant activities 38 and hepatoprotective effects. 39 In the present study, we were not able to observe any hepatic beneficial effects.…”

Section: Discussionmentioning

confidence: 99%

Fructose-Induced Fatty Liver Disease

et al. 2005

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Abstract-The most known risk factor for nonalcoholic fatty liver disease (NAFLD) is the metabolic syndrome. In this study, we characterized changes in liver pathology, hepatic lipid composition, and hepatic iron concentration (HIC) occurring in rats given fructose-enriched diet (FED), with and without therapeutic maneuvers to reduce blood pressure and plasma triglycerides. Rats were given FED or standard rat chow for 5 weeks. Rats on FED were divided into 4 groups: receiving amlodipine (15 mg/kg per day), captopril (90 mg/kg per day), bezafibrate (10 mg/kg per day) in the last 2 weeks, or a control group that received FED only. FED rats had hepatic macrovesicular and microvesicular fat deposits develop, with increase in hepatic triglycerides (ϩ198%) and hepatic cholesterol (ϩ89%), but a decrease in hepatic phospholipids (Ϫ36%), hypertriglyceridemia (ϩ223%), and hypertension (ϩ15%), without increase in HIC. Amlodipine reduced blood pressure (Ϫ18%), plasma triglycerides (Ϫ12%), but there was no change in hepatic triglycerides and phospholipids concentrations. Captopril reduced blood pressure (Ϫ24%), plasma triglycerides (Ϫ36%), hepatic triglycerides (Ϫ51%), and hepatic macrovesicular fat (Ϫ51%), but increased HIC (ϩ23%), with a borderline increase in hepatic fibrosis. Bezafibrate reduced plasma triglycerides (Ϫ49%), hepatic triglycerides (Ϫ78%), hepatic macrovesicular fat (Ϫ90%), and blood pressure (Ϫ11%

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Section: Discussionmentioning

confidence: 99%

Fructose-Induced Fatty Liver Disease

et al. 2005

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“…Earlier literature shows that the verapamil reduces the VEGF formation and hence angiogenesis. The potency of antioxidant activity and VEGF inhibition activity is verapamil > diltiazem, this could be the possible reason why verapamil has shown better anti-angiogenic effect then diltiazem [28][29][30] . Ethosuximide has not shown any anti-angiogenic effect in both the models of angiogenesis.…”

Section: Discussionmentioning

confidence: 97%

“…In the blood capillaries, the formation of superoxide anions (O 2-) and free radicals considered as a vital factor responsible for endothelial dysfunction 29 . possesses antioxidant and free radical scavenging effects this actions of verapamil might have protected the endothelium from oxidative damage 28 .…”

Section: Discussionmentioning

confidence: 99%

"Comparative Experimental Studies of Few L-Type and T-Type Ca+2 Channel Blockers Against In-Ovo and In-Vitro Models of Angiogenesis"

Chidrawar

Imran

2017

Asian Journal of Pharmaceutical Research and Health Care

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Angiogenesis is the development of new blood vessels from pre-existing one. The ion-channels on endothelium plays vital role in cell proliferation and related angiogenesis. We aimed to investigate the effects of L-type (Verapamil and Diltiazem) and T-type (Ethosuximide) Calcium Channel Blockers (CCBs) on neovascularization. The effects on neovascularization were investigated by in-ovo (CAM, Chick Chorioallantoic membrane) and in-vitro (aortic ring assay) methods. Each test drug was tested for at least 3 doses and the anti-angiogenic effect was compared with Suramin as standard and normal control groups. Various vital parameters were recorded during the experiment like the number of blood capillaries, sprouts formation, angiogenic score etc. The L-type Ca 2+ channel blockers Verapamil at the dose of 50µM, 110 and 220 µM/disk has shown significant (p < 0.001) reduction in the number of branching points in CAM assay. For the further confirmation, angiogenic activity was evaluated in vitro by rat aortic ring assay method; the area of sprouts was reduced by the medium and high dose of verapamil. Diltiazem has demonstrated modest anti-angiogenic activity by both the models, whereas T-type calcium channel blocker ethosuximide has not shown any effect on the neovascularization. Among all the tested drugs verapamil has shown the promising anti-angiogenic property. Thus verapamil and diltiazem may have antiangiogenic activity defines novel beneficial effects in angiogenic mediated pathological conditions in addition to their main indications in cardiovascular complications.blood capillaries supplement cancer growth by supplying nutrients, oxygen and by taking away waste products. Angiogenesis also supports Metastasis 5 . Angiogenesis is sequential and highly co-ordinated system involves several steps including basement membrane proteolysis, migration of individual endothelial cells, and endothelial cell proliferation 6 . Inhibition of angiogenesis and arresting development of blood capillaries has emerged as a promising strategy for the treatment of cancer 2 . Many researchers are

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“…By donating hydrogen(s), DHPs could conceivably form pyridinium or pyridine analogs with an even greater number of conjugated double bonds and potential to support radical and cation formation. The very high membrane partition coefficients displayed by DHPs (Mason et al, 1999) could determine their ability to accumulate at target site(s).…”

Section: Involvement Of Flavoprotein Dehydrogenase(s)mentioning

confidence: 99%

“…The activity of compounds within each group also varies (Table 3), and this might be due to the influence of phenyl ring substituents on donor acidity and on resonance stabilization of reaction intermediates (Solomons, 1994). Another important determinant of reactivity could be the membrane partition coefficient (Mason et al, 1999).…”

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confidence: 99%

Polyphenolic Antioxidants Mimic the Effects of 1,4-Dihydropyridines on Neurotensin Receptor Function in PC3 Cells

Carraway

Hassan²,

Cochrane³

2004

J Pharmacol Exp Ther

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This study aimed to determine the mechanism(s) by which 1,4-dihydropyridine Ca 2ϩ channel blockers (DHPs) enhance the binding of neurotensin (NT) to prostate cancer PC3 cells and inhibit NT-induced inositol phosphate formation. Earlier work indicated that these effects, which involved the G proteincoupled NT receptor NTR1, were indirect and required cellular metabolism or architecture. At the micromolar concentrations used, DHPs can block voltage-sensitive and store-operated Ca 2ϩ channels, K ϩ channels, and Na ϩ channels, and can inhibit lipid peroxidation. and [Na ϩ ], we showed that these ions did not contribute to either effect. For a series of DHPs, the activity order for effects on NTR1 function followed that for antioxidant ability. Antioxidant polyphenols (luteolin and resveratrol) mimicked the effects of DHPs and showed structural similarity to DHPs. Antioxidants with equal redox ability, but without structural similarity to DHPs (such as ␣-tocopherol, riboflavin, and N-acetyl-cysteine) were without effect. A flavoprotein oxidase inhibitor (diphenylene iodonium) and a hydroxy radical scavenger (butylated hydroxy anisole) also displayed the effects of DHPs. In conclusion, DHPs indirectly alter NTR1 function in live cells by a mechanism that depends on the drug's ability to donate hydrogen but does not simply involve sulfhydryl reduction.

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Antioxidant properties of calcium antagonists related to membrane biophysical interactions

Cited by 105 publications

References 20 publications

Fructose-Induced Fatty Liver Disease

Fructose-Induced Fatty Liver Disease

"Comparative Experimental Studies of Few L-Type and T-Type Ca+2 Channel Blockers Against In-Ovo and In-Vitro Models of Angiogenesis"

Polyphenolic Antioxidants Mimic the Effects of 1,4-Dihydropyridines on Neurotensin Receptor Function in PC3 Cells

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