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Quenching activities of common hydrophilic and lipophilic antioxidants against singlet oxygen using chemiluminescence detection system

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  • Fuji Chemical Industries Co. Ltd.

Abstract and Figures

The singlet oxygen quenching activities among common hydrophilic and lipophilic antioxidants such as polyphenols, tocopherols, carotenoids, ascorbic acid, coenzyme Q10 and α-lipoic acid were recorded under the same test condition: the chemiluminescence detection system for direct 1O2 counting using the thermodissociable endoperoxides of 1,4-dimethylnaphthalene as 1O2 generator in DMF : CDCl3 (9 : 1). Carotenoids exhibited larger total quenching rate constants than other antioxidants, with astaxanthin showing the strongest activity. α-Tocopherol and α-lipoic acid showed considerable activities, whereas the activities of ascorbic acid, CoQ10 and polyphenols were only slight; these included capsaicin, probucol, edaravon, BHT and Trolox. This system has the potential of being a powerful tool to evaluate the quenching activity against singlet oxygen for various hydrophilic and lipophilic compounds.
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VOLUME 11 (2007)
Quenching Activities of Common Hydrophilic and Lipophilic Antioxidants
against Singlet Oxygen Using Chemiluminescence Detection System
Yasuhiro Nishida*, Eiji Yamashita and Wataru Miki
Institute for Food Science Research, Fuji Chemical Industry CO., Ltd., 55 Yokohoonji, Kamiichi, Toyama 930-0397,
Japan
The singlet oxygen quenching activities among common hydrophilic and lipophilic antioxidants such as
polyphenols, tocopherols, carotenoids, ascorbic acid, coenzyme Q10 and α-lipoic acid were recorded under the
same test condition: the chemiluminescence detection system for direct 1O2 counting using the
thermodissociable endoperoxides of 1,4-dimethylnaphthalene as 1O2 generator in DMF : CDCl3 (9 : 1).
Carotenoids exhibited larger total quenching rate constants than other antioxidants, with astaxanthin showing
the strongest activity. α-Tocopherol and α-lipoic acid showed considerable activities, whereas the activities of
ascorbic acid, CoQ10 and polyphenols were only slight; these included capsaicin, probucol, edaravon, BHT
and Trolox. This system has the potential of being a powerful tool to evaluate the quenching activity against
singlet oxygen for various hydrophilic and lipophilic compounds.
1. Introduction
Living organisms possess defense mechanisms
against oxidative damage. One of the most important
ways is using an antioxidants, such as ascorbic acid,
polyphenols, coenzyme Q10 (CoQ10), tocopherols or
carotenoids [2], for quenching and/or scavenging
against reactive oxygen species (ROS).
Singlet oxygen (1O2) is a non-radical ROS with
one of the strongest activities. It directly damages onto
biological lipids, proteins and DNA, which are related
to serious diseases such as diabetes, hypertension and
cancer [1,2]. It would be valuable to search an effective
quencher against 1O2 and to develop its methodology.
Di Mascio [3] reported that lycopene showed the
highest activity among carotenoids and tocopherols by
Germanium photodiode detection system in EtOH :
CHCl3 : H2O (50 : 50 : 1) using the thermodissociable
endoperoxides of a naphthalene derivative (NDPO2) as
a 1O2 generator. One of the authors [4] evaluated the
activities of marine carotenoids and α-tocopherol in
two solvent systems, CDCl3 and CDCl3 : CD3OD (2 :
1) by the chemiluminescence detection system for
direct 1O2 counting using the thermodissociable
endoperoxides of 1,4-dimethylnaphthalene (EDN) as
1O2 generator. And it was found that astaxanthin
showed the strongest activity.
The activities of carotenoids and tocopherols were
revealed by both studies, whereas those of the other
compound groups remain largely unknown. We
therefore wanted to compare the activities of common
antioxidants in nature such as ascorbic acid,
polyphenols, α-lipoic acid, CoQ10 and others to those
of carotenoids and tocopherols. Here we report the
direct comparison of the quenching activities against
1O2 among the antioxidants with not only lipophilic but
hydrophilic property under the same test conditions.
*Corresponding author. E-mail: y-nishida@fujichemical.co.jp
Abbreviations:
BHT, butyleted hydroxytoluene; CoQ10, coenzyme Q10; EDN, endoperoxides of 1,4-dimethyl naphthalene;
EGCG, epigallocatechin gallate; LDL, low-density lipoprotein; NDPO2, naphthalene-1,4-dipropionate
endoperoxide; 1O2, singlet oxygen; QOL, quality of life; ROS, reactive oxygen species.
16
Fig. 1 Chemical structures of tested compounds
17
2. Experimental
2.1. Test compounds.
Astaxanthin, lutein, α-lipoic acid, ubiquinone-10
(CoQ10), caffeic acid, quercetin, resveratrol, gallic
acid, pyrocatechol, pyrogallol, BHT and sesamin were
purchased from Sigma-Aldrich (St. Louis, MO, USA),
L(+)-ascorbic acid, α-tocopherol, probucol,
canthaxanthin and lycopene from Wako Pure Chemical
Industries, Ltd. (Osaka, Japan ), β-cryptoxanthin from
Extrasynthase (Genay, France), Trolox and edaravon
(MCI-186) from Cosmo Bio Co., Ltd. (Tokyo, Japan)
and curcumin I, (-)-epigallocatechin gallate (EGCG)
and capsaicin from Nagara Science Co., Ltd. (Gifu,
Japan). β-Carotene was a gift from Prof. H. Hashimoto
of Osaka City University. Fucoxanthin was extracted
from the brown algae Undaria pinnatifida and
Laminaria japonica. Recrystallization and/or
chromatography of all these compounds resulted in
obtaining a purity greater than 99%.
2.2. Measurement of 1O2 quenching activity
As one of the authors previously reported [4],
thermodissociable EDN prepared from
1,4-dimethylnapthalene (purchased from
Sigma-Aldrich in St. Louis, MO, USA) was used as 1O2
generator. EDN was dissolved with CDCl3 and stored
at below 0 ºC until used. It could release molecular
oxygen in the singlet state (1Δg) at 37 ºC.
Chemiluminescence emissions from 1O2 were counted
with a chemiluminescence detector, AccuFlex Lumi
400 (Aloka, Japan).
One hundred eighty micro litters of CDCl3 or a
mixture of CDCl3 : CD3OD (2:1) or DMF containing
0.01 to 50,000 μM of each compound was placed in a
thermostated glass tube (12φ X 75 mm) at 37 ºC.
Chemiluminescence counting was started just after
addition of the EDN in CDCl3 at the final concentration
of 50 mM, and was counted for 60 seconds. Both
chemiluminescence counts of a control (S0) without
any test compound, and a sample (S) with the identical
test compound were recorded. The total quenching
constant, generally for total quenching by chemical
reaction and/or physical quenching, kT = kq + kr, was
analyzed on a Stern-Volmer plot, which is based on the
following equation [5],
S0/S = 1+ kTkd
-1[Q] (1)
where kq is the physical quenching rate constant, kr is
the chemical reaction rate constant, kd is the first-order
decay rate constant of singlet oxygen in the solvent,
and [Q] is concentration of the test compounds. Total
quenching constant kT was used to evaluate the activity
of the each test compound.
3. Results and Discussion
Within the range of the concentrations actually
tested each antioxidant was dissolved in the solvent at
37 ºC.
Fig. 2 showed the Stern-Volmer plots of
astaxanthin, β-carotene, lycopene, α-tocopherol and
α-lipoic acid in CDCl3, CDCl3 : CD3OD (2 : 1) and
DMF : CDCl3 (9 : 1). A high linearity meaning more
than 0.9 of r2 value was observed in the each plot. The
plots of other test compounds were similar to those
(data not shown).
Total quenching constant (kT = kq + kr) of each test
compound is shown in Table 1. The activities of
canthaxanthin (in CDCl3), α-carotene, β-cryptoxanthin,
fucoxanthin (in CDCl3), lycopene, lutein (in CDCl3 :
CD3OD (2 : 1)), α-tocopherol (in CDCl3 : CD3OD (2 :
1)), CoQ10 and α-lipoic acid were additionally
recorded by the same method as the former study [4]
and a similar tendency was observed. Briefly,
carotenoids showed stronger 1O2 quenching activities
than α-tocopherol as well as CoQ10 and α-lipoic acid
which are recognized as common antioxidants.
In the case of carotenoids, a number of conjugated
double bonds including C=C and C=O were found to
contribute the quenching activity. In CDCl3 represented
18
as the lipophilic system, lycopene showed the largest
value. And in CDCl3 : CD3OD (2 : 1) with more
hydrophilicity, astaxanthin did so.
Both hydrophilic and lipophilic common
antioxidants were directly compared in the new system
using DMF : CDCl3 (9 : 1). All carotenoids exhibited
larger kT value than other antioxidants. Moreover,
astaxanthin showed the strongest activity among
carotenoids tested. The hydroxyl groups in the
carotenoid molecule were found to contribute slightly
to the activity in the solvent, while the carbonyl groups
were also found in CDCl3 : CD3OD (2 : 1). The values
of α-tocopherol and α-lipoic acid were relatively large.
Ascorbic acid, CoQ10 and polyphenols such as EGCG
represented as catechins, quercetin as flavonoids,
curcumin as curcumnoids, resveratrol as stilbenoids,
gallic acid as tannins, sesamin as lignan, pyrocatechol,
caffeic acid and pyrogallol had weaker activities.
Weaker activities were also noted in capsaicin,
probucol and edaravon as medicines, BHT used as an
antioxidant food additive and Trolox
(6-hydroxy-2,5,7,8-tetramethyl- chroman-2-carboxylic
acid) which is a reference substance for ORAC
(Oxygen Radical Absorbance Capacity) value. They
might rather be singlet oxygen quenchers than free
radical scavengers against superoxide anion or
hydroxyl radicals. This system has the potential of
being a powerful tool to evaluate the quenching activity
against singlet oxygen for various hydrophilic and
lipophilic compounds.
Overall, astaxanthin exhibited the most potent
singlet oxygen quenching activity among the
compounds tested in this study because it showed a
stable superior property under the three different
conditions. Astaxanthin is widely distributed in fish
and shellfish, crustaceans, zoo- and phyto-planktons,
bacteria and so on, particularly in marine organisms. In
fact, the first isolation and identification was
accomplished in 1938 from the lobster, Astacus
gammarus [6], and numerous studies were carried out
over a long period. It is reported that the biological
activity of astaxanthin originated from potent 1O2
quenching and lipid peroxidation suppressing activities
[7]. Various human benefits for human health have
been recognized to date: immunomodulation [8],
anti-stress [9], anti-inflammation [10], LDL cholesterol
oxidation suppression [11], enhanced skin health [12],
improved semen quality [13], attenuation of eye fatigue
[14], sports performance and endurance enhancement
[15], limitations on exercised induced muscle damage
[16], limitations of diabetic nephropathy [17],
improvement of hypertension [18] and metabolic
syndrome [19]. Astaxanthin obviously plays an
important role in promoting QOL to prevent diseases
and maintain a healthy life.
Further study is needed for the evaluation of lipid
peroxidation suppressing activity among common
hydrophilic and lipophilic antioxidants based on this
experiment.
Fig.2 Stern-Volmer plots of some tested compounds
19
4. Acknowledgments
We thank Dr. H. Hashimoto of Osaka City
University for supplying β-carotene. We are also
indebted to Dr. V. Wood and Ms. A. Miyashita of Fuji
Chemical Industry Co. Ltd. for valuable discussion.
5. References
[1] Min, D.B., and Boff, J.b., 1, 58-72 (2002)
[2] Wagner, J.R., Motchnik, P. A., Stocker, R., Sies, H.,
and Ames, B. N., J. Biol. Chem., 268(25),
18502-18506 (1993).
[3] Di Mascio, P., Kaiser, S.P., Devasagayam, T.P.,
Sies, H., Adv. Exp. Med. Biol., 283, 71-77 (1991).
[4] Shimidzu, N., Goto, M., and Miki, W.,. Fish. Sci.,
62, 134–137 (1996).
[5] Di Mascio, P., Sundquist, A. R., Devasagayam, T.P.,
and Sies, H., Methods Enzymol., 213, 429-438
(1992).
[6] Kuhn, R., and Sorensen, N.A., Ber. Deut. Bot. Ges.,
71, 1879 (1938).
[7] Miki, W., Pure & Appl. Chem., 63, 141-146 (1991).
[8] Jyonouchi, H., Zhang, L., and Tomita, Y.,
Natr.Cancer., 19, 269-280 (1993).
[9] Yung, S., Asami, S., Toyota, H., Fujii, W., Suwa, Y.,
and Tanaka, R., Japanese J. Nutr. Food, 50,
423-428 (1997).
[10] Bennedsen, M., Wang, X., Willen, R., Wadstroem,
T., and Andersen, L.P., Immun Letters, 70,
185-189 (1999).
[11] Iwamoto, T., Hosoda, K., Hirano, R., Kurata, H.,
Matsumoto, A., Miki, W., Kamiyama, M., Itakura,
H., Yamamoto, S., and Kondo, K., Inhibition of
low-density lipoprotein oxidation by astaxanthin.
J. Atheroscler. Thromb., 7, 216-222 (2000).
[12] Yamashita, E., Carotenoid Science, 10, 91-95
(2006).
[13] Combaire, F.H., Garem, T.EI., Mahmound, A.,
Eertmas, F., and Schoonjans, F., Asian J. Androl.,
7(3), 257-262 (2005).
[14] Nagaki, Y., Hayasaka, S., Yamada, T., Hayasaka,
Y., Sanada, M., and Uonomi, T., J. Trd. Med., 19,
170-173 (2002).
[15] Sawaki, K., Yoshigi, H., Aoki, K., Koikawa, N.,
Azumane, A., Kaneko, K., and Yamaguchi, M., J.
Clinical Therap. & Med., 18, 73-88 (2002).
[16] Aoi, W., Naito, Y., Sakuma, K., Kuchide, M.,
Tokuda, H., Maoka, Y., Toyokuni, S., Oka, S.,
Yasuhara, M., and Yoshikawa, T., Antioxid Redox
Signal., 5, 139-144 (2003).
[17] Naito, Y., Uchiyama, K., Aoi, W., Hasegawa, G.,
Nakamura, N., Yoshida, N., Maoka, T., Takahashi,
J., and Yoshikawa, T., BioFactors, 20, 49-59
(2004).
[18] Hussein, G., Goto, H., Oda, S., Sankawa, U.,
Matsumoto, K., and Watanabe, H., Biol. Pharm.
Bull., 29(4), 684-688 (2006).
[19] Hussein, G., Nakagawa, T., Goto, H., Shimada, Y.,
Matsumoto, K., Sankawa, U., and Watanabe, H.,
Life Sciences, 80(6), 522-529 (2007).
Table 1. Total singlet oxygen quenching rate constants
Astaxanthin
Canthaxanthin
α
- Carotene
β- Carotene
β- Cryptoxanthin
Fucoxanthin
Lycopene
Lutei n
Zeaxanthi
n
L - Ascorbi c a cid
α
- Toc o p h er o l
α
- Lipoic acid
Ubiquinone- 10
BHT
Caffeicacid
Curcumi
n
I
( - ) - Epigallocatechin gallate
Gallic aci
Pyrocatechol
Pyrogallol
Quercetin
Resveratrol
Sesamin
Capsaicin
Probucol
Edaravon
Trolox
Compound Tested Concentration
(
μ
M
0.01- 15
0.01- 15
0.01- 15
0.01- 15
0.01- 15
0.01- 15
0.01- 15
0.01- 15
0.01- 15
20- 50,000
10- 20,000
10- 10,000
10- 3,000
10- 10,000
10- 10,000
10- 10,000
10- 6,000
10- 10,000
10- 10,000
10- 10,000
10- 10,000
10- 10,000
10- 5,000
10- 10,000
10- 10,000
10- 10,000
10- 20,000
k
T
(10
9
M
-1
s
-1
)
CDCl
3
CDCl
3
/CD
3
OD (2:1) DMF/CDCl
3
(9:1)
2.2
2.2
0.66
2.2
2.0
0.29
3.0
0.61
2.0
-
0.020
0.056
0.0019
-
-
-
-
-
-
-
-
-
-
-
-
-
-
1.8
1.3
0.23
0.28
0.27
0.075
1.4
0.26
0.73
-
0.0039
0.038
0.0021
-
-
-
-
-
-
-
-
-
-
-
-
-
-
5.4
2.0
0.93
1.1
1.7
0.97
3.4
2.1
3.4
0.00089
0.049
0.072
0.0068
0.0040
0.0023
0.0036
0.0096
0.0023
0.0055
0.0055
0.0018
0.0018
0.0012
0.0021
0.00044
0.0067
0.011
20
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... The increase in fat oxidation at low intensity after ET was greater in AX (placebo 0. 23 ± 0.15 g vs. AX 0.76 ± 0.18 g), and was associated with reduced carbohydrate oxidation and improved exercise efficiency in men, but not in women. 14.4% (± 6.2%, p < 0.02), tibialis anterior muscle size (cross-sectional area, CSA) by 2.7% (± 1.0%, p < 0.01), and specific impulse increased by 11.6% (MVC/CSA, ± 6.0%, p = 0.05), respectively, whereas placebo treatment did not alter these characteristics (MVC, 2.9% ± 5.6%; CSA, 0.6% ± 1.2%; MVC/CSA, 2.4 ± 5.7%; all p > 0.6). ...
... * In addition to AX, other nutrients such as antioxidants were used in the study.Nutrients 2022,14,107 ...
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City University for supplying β-carotene. We are also indebted to Dr. V. Wood and Ms. A. Miyashita of Fuji Chemical Industry Co
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