Vitamin E reduces accumulation of amiodarone and desethylamiodarone and inhibits phospholipidosis in cultured human cells

Honegger, Ulrich E.; Scuntaro, Isabel; Wiesmann, Ulrich

doi:10.1016/0006-2952(95)00100-e

Cited by 26 publications

(18 citation statements)

References 17 publications

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“…Until now, with known inducers of phospholipidosis such as amiodarone and desethylamiodarone, Vit-E has been shown to reduce the accumulation of these drugs and to counteract phospholipidosis biochemically evaluated by decreased cytoplasmic levels of phospholipids [69,70]. Our data contribute additional information to these reports.…”

Section: Discussionsupporting

confidence: 48%

“…Consequently, this observation contributes to different hypotheses: Vit-E might inhibit the accumulation of phospholipids in the vacuoles, Vit-E might stimulate the degradation or inhibit the synthesis of phospholipids inside the vacuoles and/or Vit-E might reestablish the traffic of phospholipids towards other cell compartments, such as the endoplasmic reticulum or the plasma membrane. Thus, the ability of Vit-E to act on phospholipid content and distribution and on key enzymes of phospholipid metabolism such as PP2A [70,71] might at least partially explain its ability to restore the activity of the PI3-K/PDK-1/Akt signalling pathway in 7KC-treated cells. However, the inability of Vit-E to restore membrane fluidity, demonstrated by fluorescence anisotropy, suggests that its positive effects would concern only minor and particular domains of the cytoplasmic membrane, such as those involved in signal transduction defined as raft microdomains.…”

Section: Discussionmentioning

confidence: 94%

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Phospholipidosis and down-regulation of the PI3-K/PDK-1/Akt signalling pathway are vitamin E inhibitable events associated with 7-ketocholesterol-induced apoptosis

Véjux

Guyot

Montange

et al. 2009

The Journal of Nutritional Biochemistry

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Section: Discussionsupporting

confidence: 48%

Section: Discussionmentioning

confidence: 94%

Phospholipidosis and down-regulation of the PI3-K/PDK-1/Akt signalling pathway are vitamin E inhibitable events associated with 7-ketocholesterol-induced apoptosis

Véjux

Guyot

Montange

et al. 2009

The Journal of Nutritional Biochemistry

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“…The antioxidant vitamin-E was shown to reduce lysosomal phospholipidosis[12] and amiodarone toxicity. [13] Vitamin-E significantly inhibited the formation of the thiobarbituric acid reactive substance, which is used as a measure of free radical mediated-lipid peroxidation in tissue homogenates.…”

mentioning

confidence: 99%

Role of vitamin-E on rat liver-amiodarone: An ultrastructural study

Zaki

Eid

2009

Saudi J Gastroenterol

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Background/Aim:Amiodarone, a class III antiarrhythmic drug, has been found to be effective in the management of patients with life-threatening ventricular arrhythmias. The aim of this study was to test whether the co administration of vitamin-E with amiodarone can reduce amiodarone-induced liver damage.Materials and Methods:Twelve male albino rats were divided into three groups (ml vegetable oil/day by oral gavages daily for 2 weeks and were used as control group. The rats of the second group received 5.4 mg amiodarone/100 gm rat dissolved in vegetable oil daily by oral gavages for 2 weeks. In the third group, the rats received 5.4 mg amiodarone and 5 mg vitamin-E/100 gram rat dissolved in 2 ml vegetable oil by oral gavages daily for 2 weeks. Two weeks after treatment, the rats were sacrificed and liver specimens were immediately taken and processed for transmission electron microscopic examinations.Results:Sections from the rat liver receiving amiodarone examined by electron microscopy showed disrupted hepatocytes with increased vacuolations. Degenerated organelles and disrupted nuclei were observed. The microvilli of bile canaliculi were disrupted and the hepatocytes showed increased lipid contents. Both endothelial cells and Kupffer cells were damaged. Phospholipids inside the mitochondria showed a loss of cristae. Sections from the liver of rats received amiodarone and vitamin-E showed lesser effects, especially in depositions of phospholipids in the mitochondria and the whole organelles and the nucleus showed minor damage in comparison to the previous group.Conclusion:Milder hepatotoxic effects are seen in rats administered amiodarone and vitamin E simultaneously suggesting that vitamin-E may play a role in amelioration of the effects of amiodarone.

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“…D-a-Tocopherol (vitamin E, a-Toc) has been shown to inhibit efficiently cellular drug accumulation and concomitant phospholipidosis during exposure of cultured cells to amiodarone (Amio) and desethylamiodarone (DEA) (Honegger et al, 1995). In the present study we investigated the mechanism and specificity of the actions of oa-Toc, its derivatives and of other lipophilic antioxidants on cellular kinetics and effects of several CADs in vitro.…”

Section: Introductionmentioning

confidence: 99%

Inhibition by vitamin E of drug accumulation and of phospholipidosis induced by desipramine and other cationic amphophilic drugs in human cultured cells

Scuntaro

Kientsch

Wiesmann

et al. 1996

British J Pharmacology

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1 Cationic amphiphilic drugs (CADs) are widely used in chronic pharmacotherapies in spite of frequently observed side effects connected with lysosomal phospholipid (PL) storage. 2 It has recently been shown that cx-tocopherol (a-Toc) inhibits drug-and PL accumulation in cell cultures chronically exposed to the CAD, amiodarone. 3 The mechanisms of a-Toc action on drug kinetics and PL storage were studied in human cultured fibroblasts exposed to single and repetitive doses of desipramine and other CADs. 4 a-Toc did not influence the initial, pH-dependent rapid phase of drug uptake. It inhibited, in a dosedependent manner, the slow and the cumulative phases of drug uptake and coincidently the accumulation of cellular PLs. 5 The inhibitory effects of c-Toc on CAD and PL accumulations depends on the ratio between CAD and a-Toc concentrations in the medium. This points to competition between a-Toc and CADs for PL complex formation. 6 Effectiveness of a-Toc on drug uptake varies among different CADs. It depends on its structural integrity but is independent of stereoisomerism. The inhibitory action is restricted to the piggyback slow drug uptake and therefore related to the proportion of membrane-mediated transport to permeation into lysosomes (rapid uptake). This proportion differs among CADs. 7 a-Toc prevents lysosomal membrane-PL storage, accelerates disintegration of PL-stores and normalizes drug-related increased membrane fluidity. This strongly suggests that a-Toc restores membrane recycling, impaired by CAD exposure.8 It remains to be tested in vivo whether cx-Toc reduces CAD side effects without interfering with drug effectiveness.

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Vitamin E reduces accumulation of amiodarone and desethylamiodarone and inhibits phospholipidosis in cultured human cells

Cited by 26 publications

References 17 publications

Phospholipidosis and down-regulation of the PI3-K/PDK-1/Akt signalling pathway are vitamin E inhibitable events associated with 7-ketocholesterol-induced apoptosis

Phospholipidosis and down-regulation of the PI3-K/PDK-1/Akt signalling pathway are vitamin E inhibitable events associated with 7-ketocholesterol-induced apoptosis

Role of vitamin-E on rat liver-amiodarone: An ultrastructural study

Inhibition by vitamin E of drug accumulation and of phospholipidosis induced by desipramine and other cationic amphophilic drugs in human cultured cells

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