Effects of new combinative antioxidant FeAOX-6 and α-tocotrienol on macrophage atherogenesis-related functions

Napolitano, Mariarosaria; Avanzi, Luca; Manfredini, Stefano; Bravo, Elena

doi:10.1016/j.vph.2006.01.019

Cited by 16 publications

(9 citation statements)

References 48 publications

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“…These results are consistent with previous findings with vitamin E (38,41) and are broadly similar to those obtained using comparable concentrations of FeAOX-6, where reductions in CE synthesis in HMDM were most marked in the presence of oxLDL compared with nLDL or acLDL (27). ␣-Tocotrienol, a vitamin E derivative, however, caused greater decreases in all cases (27). In experiments with the murine macrophage cell line J774, Furhman et al (13) have found that a comparable concentration of lycopene to that used here decreased cholesterol synthesis via inhibition of the rate-limiting enzyme for the pathway, 3-hydroxy-3-methylglutaryl reductase, and this may contribute to the decreased rate of cholesterol esterification.…”

Section: Discussionsupporting

confidence: 92%

“…2B). These results are consistent with previous findings with vitamin E (38,41) and are broadly similar to those obtained using comparable concentrations of FeAOX-6, where reductions in CE synthesis in HMDM were most marked in the presence of oxLDL compared with nLDL or acLDL (27). ␣-Tocotrienol, a vitamin E derivative, however, caused greater decreases in all cases (27).…”

Section: Discussionsupporting

confidence: 92%

“…Recent work from our laboratory, however, has shown that FeAOX-6, a synthetic compound that combines the antioxidant structural features of vitamin E and lycopene, decreased the cholesterol content of HMDM in the absence of LDL, although there was little effect in the presence of nLDL, acLDL, or oxLDL (27). In the present study, cholesterol accumulation in HMDM was unaffected by lycopene in the absence of LDL but tended to be decreased when LDL or modified LDL (acLDL or aggLDL) was present (Fig.…”

Section: Discussionmentioning

confidence: 88%

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Effects of lycopene on the induction of foam cell formation by modified LDL

Napolitano¹,

Pascale²,

Wheeler‐Jones³

et al. 2007

American Journal of Physiology-Endocrinology and Metabolism

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The effect of lycopene on macrophage foam cell formation induced by modified low-density lipoprotein (LDL) was studied. Human monocyte-derived macrophages (HMDM) were incubated with lycopene in the presence or absence of native LDL (nLDL) or LDL modified by oxidation (oxLDL), aggregation (aggLDL), or acetylation (acLDL). The cholesterol content, lipid synthesis, scavenger receptor activity, and the secretion of inflammatory [interleukin (IL)-1beta and tumor necrosis factor (TNF)-alpha] and anti-inflammatory (IL-10) cytokines was determined. Lycopene was found to decrease the synthesis of cholesterol ester in incubations without LDL or with oxLDL while triacylglycerol synthesis was reduced in the presence of oxLDL and aggLDL. Scavenger receptor activity as assessed by the uptake of acLDL was decreased by approximately 30% by lycopene. In addition, lycopene inhibited IL-10 secretion by up to 74% regardless of the presence of nLDL or aggLDL but did not affect IL-1beta or TNF-alpha release. Lycopene also reduced the relative abundance of mRNA transcripts for scavenger receptor A (SR-A) in THP-1 macrophages treated with aggLDL. These findings suggest that lycopene may reduce macrophage foam cell formation induced by modified LDL by decreasing lipid synthesis and downregulating the activity and expression of SR-A. However, these effects are accompanied by impaired secretion of the anti-inflammatory cytokine IL-10, suggesting that lycopene may also exert a concomitant proinflammatory effect.

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Section: Discussionsupporting

confidence: 92%

Section: Discussionsupporting

confidence: 92%

Section: Discussionmentioning

confidence: 88%

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Effects of lycopene on the induction of foam cell formation by modified LDL

Napolitano¹,

Pascale²,

Wheeler‐Jones³

et al. 2007

American Journal of Physiology-Endocrinology and Metabolism

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“…These results are broadly similar to those obtained in HMDM using comparable concentrations of FeAOX-6, a synthetic compound that combines the antioxidant structural features of vitamin E and lycopene. The reduction in cholesterol ester synthesis by FeAOX-6 was extremely marked in the presence of oxidized LDL [48]. The results of the in vitro studies are summarized in table 1.…”

Section: In Vitro Studiesmentioning

confidence: 99%

Effect of Lycopene and Tomato Products on Cholesterol Metabolism

Palozza

Catalano²,

Simone³

et al. 2012

Ann Nutr Metab

142

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Background/Aims: Increased ingestion of tomato, containing lycopene, has been associated with a decreased risk for atherosclerosis, although the exact molecular mechanism is still unknown. Here we review the available evidence for a direct regulation of tomato lycopene on cholesterol metabolism using results from experimental and human studies. Results: In human macrophages lycopene dose dependently reduced intracellular total cholesterol. Such an effect was associated with a decrease in cholesterol synthesis through a reduction of 3-hydroxy-3-methylglutaryl coenzyme A reductase activity and expression, a modulation of low- density lipoprotein (LDL) receptor and acyl-coenzyme A:cholesterol acyltransferase activity. An increase in cholesterol efflux through an enhancement of ABCA1 and caveolin-1 expression was also observed. In animal models of atherosclerosis, lycopene and tomato products decreased plasma total cholesterol, LDL cholesterol and increased high-density lipoprotein cholesterol. In agreement with the experimental results, most human intervention trials analyzed show that dietary supplementation with lycopene and/or tomato products reduced plasma LDL cholesterol dependently on the dose and the time of administration. Conclusions: Although lycopene and tomato products seem to possess direct hypocholesterolemic properties, more experimental studies are needed to better understand the mechanisms involved. There is also a need for more well-designed human dietary intervention studies to better clarify the role of lycopene as a hypocholesterolemic agent.

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“…Pivotal role in atherogenesis is played by macrophages, which are early site for lipid accumulation and mediate the inflammatory and immune response in the intima (Inokuchi et al 2003;Miyazawa et al 2004). Napolitano et al (2007) evaluated the effect of a-tocotrienol combined with a new compound FeAOX-6 on macrophage atherogenesis and its related functions and found that the combination induced strong dose-dependent reduction of cholesterol and reduce cholesterol accumulation in human macrophages. The extent of the reduction found with a-tocotrienol was greater than that induced by FeAOX-6.…”

Section: Anti-inflammatory Role Of Tocotrienols In Cardioprotectionmentioning

confidence: 99%

Multifaceted role of tocotrienols in cardioprotection supports their structure: function relation

2011

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Tocotrienols are a class of vitamin E which modulates several mechanisms associated with cardioprotection, anti-cancer, anti-diabetic, and neuroprotection. Unlike other Vitamin E-like compounds, tocotrienols possess inimitable properties. Quite a lot of studies have determined the cardioprotective abilities of tocotrienols and have been shown to possess novel hypocholesterolemic effects together with an ability to reduce the atherogenic apolipoprotein and lipoprotein plasma levels. In addition, tocotrienol has been suggested to have an antioxidant, anti-thrombotic, and antitumor effect indicating that tocotrienol may serve as an effective agent in the prevention and/or treatment of cardiovascular disease and cancer. The bioactivity exhibited is due to the structural characteristics of tocotrienols. Rich sources of tocotrienols which include rice bran, palm oil, and other edible oils exhibit protective effect against cardiovascular disorders. The conclusions drawn from the early literature that vitamin E group of compounds provides an inevitable role in cardioprotection is sustained in many more recent studies.

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Effects of new combinative antioxidant FeAOX-6 and α-tocotrienol on macrophage atherogenesis-related functions

Cited by 16 publications

References 48 publications

Effects of lycopene on the induction of foam cell formation by modified LDL

Effects of lycopene on the induction of foam cell formation by modified LDL

Effect of Lycopene and Tomato Products on Cholesterol Metabolism

Multifaceted role of tocotrienols in cardioprotection supports their structure: function relation

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