Antioxidant properties of ticlopidine on human low density lipoprotein oxidation

Lapenna, Domenico; Gioia, Sergio de; Ciofani, Giuliano; Bruno, Cristiana; Porreca, Ettore; Pierdomenico, Sante D.; Cuccurullo, Franco

doi:10.1016/s0014-5793(98)01166-1

Cited by 13 publications

(9 citation statements)

References 34 publications

(51 reference statements)

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“…Possible scavenging effects of amiodarone on peroxyl radicals, which are involved in lipoprotein oxidation, were investigated by assessing the ability of the drug to counteract peroxyl radical‐induced oxidation of 5‐thio‐2‐nitrobenzoic acid (TNB), resulting in decrease in TNB‐related absorbance at 412 nm ( Lapenna et al ., 1998 ). TNB was prepared by reduction of 5,5′‐dithiobis (2‐nitrobenzoic acid) with 2‐mercaptoethanol and its concentration was calculated using a molar extinction coefficient of 13,600 at 412 nm ( Lapenna et al ., 1998 ). 2,2′‐azobis (amidinopropane) dihydrochloride (AAPH) was used to generate thermally peroxyl radicals.…”

Section: Methodsmentioning

confidence: 99%

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Antioxidant activity of amiodarone on human lipoprotein oxidation

Lapenna

Ciofani

Bruno

et al. 2001

British J Pharmacology

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1 Lipoprotein oxidation is crucial in atherogenic processes. Amiodarone is a lipophilic antiarrhythmic/antianginal drug which is able to in¯uence the physicochemical status of biological lipid components. Since oxidation of lipids is a ected by their physicochemical state and amiodarone binds to lipoproteins, we hypothesized that the drug may exert an antioxidant activity on human lipoprotein oxidation. 2 Dose-dependent e ects of therapeutically achievable amiodarone concentrations (1.5, 3, 5, 7 and 10 mM) were studied on copper-catalysed oxidation of the non-HDL fraction in vitro. Amiodarone inhibited oxidation as judged by generation of thiobarbituric acid reactive substances (TBARS), lipid hydroperoxides (LOOH) and¯uorescent products of lipoperoxidation (FPL) as well as from the kinetics of conjugated diene formation. This antioxidant activity was signi®cant at 1.5 mM with total inhibition at 10 mM and an IC 50 of 4 mM. The primary in vivo metabolite of amiodarone, namely desethylamiodarone, also exhibited speci®c antioxidant properties although it was less e ective than amiodarone with an IC 50 of 7 mM. 3 In further in vivo experiments, susceptibility to copper-mediated oxidation of the non-HDL fraction was investigated before and 4 weeks after oral amiodarone administration to humans. Following treatment, signi®cant inhibition of TBARS, LOOH and FPL generation was observed in comparison with baseline levels and a placebo-treated control group, highlighting an e ective antioxidant capacity of amiodarone in vivo. 4 Amiodarone did not change lipoprotein vitamin E and phospholipid content in vivo and did not show scavenging e ects on oxidizing species involved in lipoprotein oxidation, such as peroxyl radicals, nor metal-binding/inactivating properties, suggesting that physicochemical modi®cations of lipoprotein lipids induced by the lipophilic drug may be involved in its antioxidant activity. 5 In conclusion, amiodarone, and its primary metabolite desethylamiodarone, show previously unrecognized antioxidant activity on human lipoprotein oxidation. This e ect is also evident in vivo and at therapeutically achievable drug concentrations. Thus, amiodarone may act as an antioxidant/ antiatherosclerotic agent in humans, although this issue warrants further clinical study.

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Section: Methodsmentioning

confidence: 99%

“…We also evaluated drug capacity to scavenge the stable free radical 1,1‐diphenyl‐2‐pycrylhydrazyl (DPH), resulting in DPH bleaching ( Blois, 1958 ; Lapenna et al ., 1998 ). Reaction mixtures contained 85 μ M DPH (previously dissolved in ethanol) in PBS (pH 7.4), with or without amiodarone.…”

Section: Methodsmentioning

confidence: 99%

Antioxidant activity of amiodarone on human lipoprotein oxidation

Lapenna

Ciofani

Bruno

et al. 2001

British J Pharmacology

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“…The major anti-oxidant enzyme families in organisms are superoxide dismutase (SOD), glutathione peroxidase (GPx), glutathione reductase (GR), and CAT (7)(8)(9)(10)(11). There is a balance between both the activities and the intracellular levels of these anti-oxidants that is essential for both survival and health of an organism (12,13).…”

Section: Introductionmentioning

confidence: 99%

Hepatoprotective effects of aqueous extracts from leaves of Dendropanax morbifera leveille against alcohol-induced hepatotoxicity in rats and in vitro anti-oxidant effects

Bae¹,

Kim²,

Lee³

et al. 2015

Food Sci Biotechnol

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Protective effects of Dendropanax morbifera Lev. leaves (DM) against alcohol-induced liver injury in rat hepatocytes, and rats were investigated. Cell viability increased, and normally elevated intracellular reactive oxygen species (ROS) levels were reduced in cells treated with water extracts of DM (DMW) before ethanol treatment, compared with cells treated with 200 mM ethanol. DMW administration with ethanol resulted in prevention of ethanol-induced hepatotoxicity due to reductions of serum aspartate aminotransferase and alanine aminotransferase levels. DMW supplementation reduced formation of malondialdehyde, and inhibited reductions of hepatic glutathione, catalase, glutathione-S-transferase, glutathione reductase, and glutathione peroxidase levels, compared with rats administered ethanol, and suppressed expression of cytochrome P-450 2E1 that was elevated by ethanol administration. DMW reduced blood ethanol concentrations, and enhanced alcohol dehydrogenase and alcohol dehydrogenase activities that are typically decreased by ethanol administration, compared with ethanol-administered rats. DM exerted hepatoprotective effects against alcoholinduced hepatocyte injury.

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“…Although the process of LDL oxidation remains unclear, the major mechanisms currently explored are metal ions dyshomeostasis (Swain and Gutteridge, 1995), changes in lipoxygenase and myeloperoxidase-related pathways Daugherty et al, 1994), reactive oxygen and nitrogen species generation, and alterations in the thiol status (Halliwell, 1995). In fact, endogenous and exogenous compounds with antioxidant activity have been reported to display beneficial effects against LDL oxidation (Lass et al, 1996;Lapenna et al, 1998;Alul et al, 2003;Bem et al, 2008). In view of this, we could suggest that these preliminary results indicate that the oximes tested here could be considered as a promising antiatherogenic compound.…”

Section: Discussionmentioning

confidence: 99%