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Comparative antioxidant activity of tocotrienols and the novel chromanyl-polyisoprenyl molecule FeAox-6 in isolated membranes and intact cells

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Abstract

Oxidative stress plays a pivotal role in the pathogenesis of several chronic diseases and antioxidants may represent potential tools for the prevention of these diseases. Here, we investigated the antioxidant efficiency of different tocotrienol isoforms (é-, δ-, γ-tocotrienols), and that of FeAox-6, a novel synthetic compound which combines, by a stable covalent bond, the chroman head of vitamin E and a polyisoprenyl sequence of four conjugated double bonds into a single molecule. The antioxidant efficiency was evaluated as the ability of the compounds to inhibit lipid peroxidation, reactive oxygen species (ROS) production, heat shock protein (hsp) expression in rat liver microsomal membranes as well as in RAT-1 immortalized fibroblasts challenged with different free radical sources, including 2,2′-azobis(2-amidinopropane) (AAPH), tert-butyl hydroperoxide (tert-BOOH) and H2O2. Our results show that individual tocotrienols display different antioxidant potencies. Irrespective of the prooxidant used, the order of effectiveness was:δ-tocotrienol > γ-tocotrienol = é-tocotrienol in both isolated membranes and intact cells. This is presumably due to the decreased methylation of δ-tocotrienol chromane ring, which allows the molecule to be more easily incorporated into cell membranes. Moreover, we found that FeAox-6 showed an antioxidant potency greater than that of δ-tocotrienol. Such an efficiency seems to depend on the concomitant presence of a chromane ring and a phytyl chain in the molecule, which because of four conjugated double bonds, may induce a greater mobility and a more uniform distribution within cell membrane. In view of these results, FeAox-6 represents a new potential preventive agent in chronic diseases in which oxidative stress plays a pathogenic role.

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Abbreviations

AAPH:

2,2′-azobis(2-amidinopropane)

BHT:

butylated hydroxytoluene

DCF:

6-carboxy-2′,7′-dichlorodihydrofluorescein diacetate

DMSO:

dimethyl sulfoxide

FeAOX-6:

(±)-(E)-2,5,7,8-tetramethyl-2(4,8,12-trimethyl-trideca-1,3,5,7,11-pentaenyl)chroman-6-ol)

hsp:

heat shock protein

MDA:

malondialdehyde

PBS:

phosphate buffered saline

ROS:

reactive oxygen species

TBA:

2-thiobarbituric acid

TBARS:

thiobarbituric acid reactive substances

tert-BOOH:

tert-butyl hydroperoxide

TCA:

Trichloroacetic acid

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Authors and Affiliations

  1. Institute of General Pathology, Catholic University, 00168, Rome, Italy

    Paola Palozza, Sara Verdecchia & Simona Serini

  2. Department of Pharmaceutical Sciences, Ferrara University, I-44100, Ferrara, Italy

    Luca Avanzi, Silvia Vertuani & Stefano Manfredini

  3. Department of Biomedical Sciences, 41100, Modena, Italy

    Anna Iannone

Authors
  1. Paola Palozza
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  2. Sara Verdecchia
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  3. Luca Avanzi
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  4. Silvia Vertuani
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  5. Simona Serini
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  6. Anna Iannone
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  7. Stefano Manfredini
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Correspondence to Paola Palozza.

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Palozza, P., Verdecchia, S., Avanzi, L. et al. Comparative antioxidant activity of tocotrienols and the novel chromanyl-polyisoprenyl molecule FeAox-6 in isolated membranes and intact cells. Mol Cell Biochem 287, 21–32 (2006). https://doi.org/10.1007/s11010-005-9020-7

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