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Advances in food technology and
nutritional sciences
Open Journal http://dx.doi.org/10.17140/AFTNSOJ-1-123
Adv Food Technol Nutr Sci Open J
ISSN 2377-8350
Oxidation of Polyunsaturated Fatty Acids
and its Impact on Food Quality and
Human Health
Ling Tao*
Department of Animal Science, Cornell University, Ithaca, NY, USA
*Corresponding author:
Ling Tao, PhD
Department of Animal Science
Cornell University
149 Morrison Hall
Ithaca, NY 14853, USA
E-mail: Lt364@cornell.edu
Article History:
Received: November 24th, 2015
Accepted: December 17th, 2015
Published: December 18th, 2015
Citation:
Tao L. Oxidation of polyunsaturated
fatty acids and its impact on food
quality and human health. Adv Food
Technol Nutr Sci Open J. 2015; 1(6):
134-141.
Copyright:
© 2015 Tao L. This is an open ac-
cess article distributed under the
Creative Commons Attribution Li-
cense, which permits unrestricted
use, distribution, and reproduction
in any medium, provided the origi-
nal work is properly cited.
Volume 1 : Issue 6
Article Ref. #: 1000AFTNSOJ1123
Mini Review
Page 134
ABSTRACT
For many years, both preclinical and clinical studies have provided evidences to sup-
port the benecial effects of ω-3 Polyunsaturated fatty acids (PUFAs), particularly Eicosapen-
taenoic acid (EPA) and Docosahexaenoic acid (DHA) in the prevention of chronic diseases.
However, recently, an increasing number of studies reported adverse or contradictory effects
of ω-3 PUFAs on human health. While dose and experimental condition need to be considered
when evaluating these effects, oxidation of PUFAs also serves as an important factor contribut-
ing to the inconsistent results. In fact, oxidation of PUFAs happens frequently during food pro-
cessing and storage, cooking and even after food ingestion. The free radicals and metabolites
generated from PUFA oxidation may adversely affect food quality and shelf life by producing
off-avors and reducing nutritional values. The impact of PUFA oxidation in human health is
more complicated, depending on the concentration of products, disease background and targets.
This review will introduce different types of PUFA oxidation, discuss its impact on food quality
and human health and provide some thoughts for the future research directions.
KEYWORDS: Polyunsaturated fatty acids; Oxidation; Food quality; Human health.
ABBREVIATIONS: ALA: α-Linolenic acid; LOX: Lipoxygenase; COX: Cyclooxygenase; MaR:
Maresin; CYP: Cytochromes P450; PD/NPD: Protectin/neuroprotectin; DHA: Docosahexae-
noic acid; PL: Phospholipase; EPA: Eicosapentaenoic acid; PUFA: Polyunsaturated fatty acid;
GST: Glutathione S-transferase; RvD: D-series resolvin; HHE: 4-Hydroxy-2-hexenal; RvE: E-
series resolvin; HNE: 4-Hydroxy-2-nonenal; FAO: Food and Agriculture Organization; WHO:
World Health Organization; AHA: American Heart Association.
INTRODUCTION
Over the past few decades, chronic diseases including cardiovascular diseases, obesity,
diabetes and cancer have increased rapidly in the USA and other countries of the world.1 Diet
and nutrition are important factors in the maintenance and promotion of good health throughout
the entire life. By far, both preclinical and clinical studies have shown that ω-3 Polyunsatu-
rated fatty acids (PUFAs) in particular Eicosapentaenoic acid (EPA) and Docosahexaenoic acid
(DHA) exert heath benecial effects on cardiovascular diseases, diabetes, cancer and so on.2-5
This leads to institutions worldwide publishing recommendations on the intake of EPA and
DHA. For instance, Food and Agriculture Organization (FAO) and World Health Organization
(WHO) recommend adults to take 0.25-2 g EPA+DHA per day.6 American Heart Association
(AHA) recommends daily intake of 0.5-1 g EPA+DHA per day per adult.7
However, as reviewed by Weylandt et al more recently, there are controversial re-
sults regarding to the health efcacy of ω-3 PUFAs.8 On one hand, the dose and experimental
designs may contribute to the variation in results. On the other hand, with the nature of un-
saturated bonds, PUFAs are prone to oxidation which generates various metabolites as well as
reactive oxygen species. The extent of oxidation and the resulting metabolites may positively
or negatively affect the efcacy of PUFAs. This review will introduce different types of PUFA
Advances in food technology and
nutritional sciences
Open Journal http://dx.doi.org/10.17140/AFTNSOJ-1-123
Adv Food Technol Nutr Sci Open J
ISSN 2377-8350
Page 135
oxidation and discuss the effects of oxidation on food quality
and human health.
ENZYMATIC AND NON-ENZYMATIC OXIDATION OF PUFAs
With multiple unsaturated bonds, PUFA is susceptible
to oxidation, which is categorized into non-enzymatic oxida-
tion and enzymatic oxidation. Non-enzymatic oxidation can
be further divided into autoxidation (mediated by free radicals)
and photooxidation (mediated by ultraviolet or singlet oxygen).
In cells, several types of enzymes including Cyclooxygenases
(COXs), Lipoxygenases (LOXs) and Cytochromes P450 (CYPs)
are able to oxidize PUFAs and generate various metabolites.9
Non-Enzymatic Oxidation
In autoxidation, the reaction is mediated by free radi-
cals, giving rise to a lipid hydroperoxide as the primary oxida-
tion product.10 In many cases, hydroperoxides can be further
oxidized to ketones and ultimate malonaldehyde.11 Hydroxy al-
kenals such as 4-Hydroxy-2-nonenal (HNE), generated by per-
oxidation of ω-6 PUFAs,12-14 and 4-Hydroxy-2-hexenal (HHE),
a product from peroxidation of ω-3 PUFAs15-17 are also widely-
studied autoxidative products of PUFAs. Apart from autooxida-
tion, PUFAs are susceptible to light-induced photooxidation:
photochemical oxidation and photosensitized oxidation.18 The
former one is initiated during exposure to ultraviolet irradia-
tion. Photosensitized oxidation, instead, requires photosensitiz-
ers (i.e. chlorophyll, hemeprotein, riboavin and synthetic dyes)
and visible light.19 The reaction can be categorized into two
types: Type I reaction involves the production of free radicals
by interaction of the excited sensitizer with a substrate; Type
II reaction involves generation of singlet oxygen which further
reacts with PUFAs to produce hydroperoxides.20,21 In this case,
vegetable oils with chlorophyll-like pigments are likely to un-
dergo photooxidation during storage.
Enzymatic Oxidation
In enzymatic oxidation, Phospholipases A2 (PLA2) is
the major phospholipase that cleaves phospholipids at the sn-2
position resulting in free PUFAs and lysophospholipids.22 Af-
ter freeing from membrane, PUFAs can be further catalyzed by
COXs (COX1 or COX2) to form prostaglandin H2. It is unstable
and can be converted into various prostanoids depending on the
cellular prevalence of terminal prostanoid synthases.23,24 In ad-
dition to COX, free fatty acids can be converted by LOXs to
form hydroperoxides. LOXs belong to a family of dioxygenases
which catalyze the insertion of molecular oxygen into PUFAs
with at least one cis, cis-1,4-pentadiene in the structure.25 Some
of the LOX-catalyzed products have recently been discovered as
potent lipid mediators. For example, enzymatic oxygenation of
EPA yields new metabolites, named E-series Resolvins (RvEs),
which were the rst omega-3 lipid mediators reported to resolve
inammation via receptor-specic actions.26-28 Likewise, DHA
can form D-series Resolvins (RvDs),29,30 Protectins/neuroprotec-
tins (PDs/NPDs)31-33 and Maresins (MaRs)34-36 through enzymes-
mediated oxygenation. Those metabolites have been widely
studied to dampen or resolve inammation, protect from renal
or brain dysfunctions, etc. COXs and LOXs can also convert ω-3
and ω-6 PUFAs into different series of prostaglandins, throm-
boxanes and leukotrienes.37 CYPs are better known for their role
in xenobiotic metabolism. However, they can also transform
PUFAs to epoxy-, monohydoxylated-and dihydroxylated-me-
tabolites. Recent work using recombinant human CYP enzymes
has identied the predominant products from the expoxidation
of EPA and DHA as 17,18-epoxyeicosatetraenoic acid and ep-
oxy docosapentaenoic acid, respectively.38
IMPACT OF PUFA OXIDATION ON FOOD QUALITY
Plant oils and sh are known as major sources of ω-3
PUFAs. Soybean oil, canola oil are commonly consumed oil
and are rich in α-Linolenic acid or Alpha-linolenic acid ((ALA),
7.8-9.2%), while some fatty sh including salmon, sardine, and
menhaden contain abundant EPA and DHA (17%-27% of total
fatty acids). Other dietary sources of ω-3 PUFAs include nuts,
seeds, egg yolk, etc.39,40 With the recognition of the health ben-
ecial effects of ω-3 PUFAs, there is a growing industry provid-
ing novel sources of ω-3 PUFAs such as sh oil capsules, algae
products and food enriched with ω-3 PUFAs.41 Our lab recently
used defatted green microalgal biomass to enrich ω-3 PUFAs in
chicken meat42 and eggs (unpublished).
Susceptibility of lipid peroxidation in food depends on
the lipid composition, the presence of prooxidants and antioxi-
dants, oxygen levels, temperature, light and processing meth-
ods.43 PUFA-rich foods are more susceptible for lipid oxidation.
Likewise, presence of prooxidants such as redox active metals
(Fe, Cu) and hemeproteins, exposure to high oxygen levels and
high temperature may accelerate oxidation process. Lipid oxi-
dation often brings problems in food processing and storage.
First, it negatively affects food avor due to the formation of
aldehydes and ketones. Oxidation of PUFAs produces a com-
plex mixture of volatile secondary oxidation products, and these
cause particularly objectionable off-avors.44 For example, soy-
bean oil can undergo “avor reversion”, a type of light-induced
oxidation.45 It has been suggested that the oxidation of ALA in
soybean oil is responsible for the formation of 2-pentylfuran
and its isomer, which may result in avor reversion.46 Butter en-
riched with unsaturated fatty acids or conjugated linoleic acid
may be susceptible to off-avor by generation of oxidized prod-
ucts including 3-methyl-1H-indole (mothball-like), pentanal
(fatty), heptanal (green) and butanoic acid (cheesy).47 Second,
lipid oxidation may reduce the nutritional value by causing the
destruction of essential fatty acids and the lipid-soluble vitamins
A, D, E, and K as well as the decrease in caloric content.48 Third,
free radicals and metabolites formed during oxidation may exert
adverse effects on human health.49 More details of impact on hu-
man will be discussed in the next section.
Given lipid oxidation-triggered negative effects, mul-
Advances in food technology and
nutritional sciences
Open Journal http://dx.doi.org/10.17140/AFTNSOJ-1-123
Adv Food Technol Nutr Sci Open J
ISSN 2377-8350
Page 136
tiple methods have been applied to reduce or prevent lipid oxida-
tion so as to improve the food quality. The most commonly used
method is addition of antioxidants. Since the 1940’s, it is known
that vitamin E is a major lipophilic chain-breaking antioxidant
which protects tissue PUFAs against peroxidation50 Serfert et
al found a combination of tocopherols (rich in the δ-derivative
and low in the α-derivative), ascorbyl palmitate and trace metal
chelators (lecithin or citrem) efciently stabilized the oil during
microencapsulation. Addition of rosemary extract in the micro-
encapsulated oil further retarded autoxidation during storage.51
Besides vitamin E, other vitamins or precursors like ascorbic
acid and β-carotene were shown antioxidant activity in food
system.18,52 Plant bioactive compounds particularly polyphenols
have been widely reported to have antioxidant effects. For ex-
ample, apple skin extracts prepared from “Northern Spy” culti-
var were found effective in reducing the lipid oxidation induced
by heat, Ultraviolet (UV) light and peroxyl radicals.53 Although
it is plausible that natural polyphenols could prevent lipid oxida-
tion, the approach of incorporating polyphenols into food and
the effects of polyphenol additives on food avor are not com-
pletely understood. In addition to the antioxidant supplementa-
tion, other methods are used to reduce lipid oxidation. Arruda et
al reported that using nitrogen ushing to remove oxygen in the
headspace of bottled soybean oil increased the sensory quality
during storage. Shelf life can also be increased from 60 up to 180
days as the initial oxygen concentration is reduced from >15%
to <3%.54 Larsen et al found that cups with a high light barrier
(incorporation of a black pigment into the packaging material)
can sufciently protect the sour cream from getting rancid due to
photooxidation.55
IMPACT OF PUFA OXIDATION ON HUMAN HEALTH
In human body, PUFA is susceptible to oxidation un-
der the exposure of free radicals and enzymes such as COXs,
LOXs and CYPs. An increasing number of studies have been
conducted to identify the oxidation pathway of PUFAs and re-
lated metabolites. However, the impact of PUFA oxidation on
human health remains elusive.
HNE, a product from ω-6 oxidation of PUFAs, has been
found in many diseases including atherosclerosis,56,57 neurode-
generative diseases,58,59 cancer60,61 and so on. Indeed, Uchida et
al have recently found that HNE markedly induced intracellular
ROS production in cultured rat hepatocytes RL34 cells.62 This
pro-oxidant effect of HNE was also observed in human neuro-
blastoma SH-SY5Y cells.63 Awada et al reported that oxidized
PUFAs (rich in HNE and HHE) induced oxidative stress and in-
ammation in mice and in human intestinal Caco-2/TC7 cells.64
In human trials, Jenkinson et al also found that high PUFA diet
(15% PUFA) signicantly increased whole blood oxidized glu-
tathione and urinary thiobarbituric acid reactive substances, in-
dices of oxidative stress, in healthy male subjects.65 Interestingly,
PUFA oxidation products have also been reported to activate
antioxidant pathways which detoxify cytotoxic xenobiotics. For
instance, HNE has been shown to enhance the gene and protein
expression of class P Glutathione S-Transferase (GST-P) as well
as the total GST activity in normal rat liver epithelial cells.66
HNE can also activate antioxidant response element, leading
to the induction of class A GST isozymes, such as GSTA1 and
GSTA4, in rat clone 9 hepatoma cells.67 In addition, HHE up-
regulated nuclear factor, erythroid 2-like 2, an important regula-
tor of antioxidant responses in the heart of high fat-fed mice.68
The bi-directional effects of HNE or HHE are concentration de-
pendent. HNE at concentration lower than 10 μM tends to exert
benecial effects while higher concentrations may have toxic
effects.69 As supported by Zhang et al, treating cardiomyocytes
with small, subtoxic doses (5 μM) of HNE offered protection
from subsequent exposure to toxic doses (>=20 μM).70
Over a decade, a growing number of PUFA metabolites
have been discovered, including ω-3 PUFAs-derived resolvins,
protectins, maresins, prostaglandin-3-, thromboxane-3- and
leukotriene-5-series as well as ω-6 PUFA-derived prostaglan-
din-2-, thromboxane-2- and leukotriene-4-series.37,71 ω-3 PU-
FA-derived metabolites have shown potent anti-inammatory,
tissue protective and resolution-stimulating functions. For in-
stance, RvDs and PD1/NPD1 inhibit neutrophil inltration into
injured kidneys, block toll-like receptor-mediated inammatory
activation of macrophages and mitigate renal dysfunctions.72
Recently, Chiang et al demonstrated a previously unrecognized
role of GPR18 as a receptor for RvD2 that stimulates effero-
cytosis and mediates the resolution of inammation.73 Anoth-
er type of lipid mediator, MaR1 and MaR2 were identied to
have potency at enhancing human macrophage phagocytosis
and efferocytosis.34,74 ω-3 PUFAs-derived prostaglandin-3- and
leukotriene-5-series have been found to exert anti-arrhythmic
and anti-inammatory effects, respectively. By contrast,
ω-6 PUFAs-derived prostaglandin-2-series have shown pro-
arrhythmic effects and leukotriene-4-series from ω-6 PUFAs
have presented pro-inammatory effects.37,75 This indicates that
enzymatic oxidation products of ω-3 and ω-6 PUFA may exert
opposing effects on human health.
From current studies, we learnt that more PUFAs do
not necessarily yield better effects as they may undergo oxida-
tion and produce metabolites that exert adverse effects at high
levels. Co-supplementation with antioxidants such as vitamin C
and vitamin E may reduce autoxidation of PUFAs and poten-
tially enhance the efcacy. In addition, increasing ω-3 to ω-6
ratio in the diet is likely to produce more benecial metabolites,
thereby enhancing efcacies of PUFAs. The optimal dose of PU-
FAs, antioxidant supplementation as well as ω-3 to ω-6 ratio,
however, require additional research evidences.
CONCLUSION
As summarized in Figure 1, through non-enzymatic
and enzymatic oxidation, PUFAs are transformed to various
metabolites. In most cases, oxidation of PUFAs results in off-
avors and reduction of food quality and shelf life. The oxida-
tion may induce oxidative stress and inammation when the
Advances in food technology and
nutritional sciences
Open Journal http://dx.doi.org/10.17140/AFTNSOJ-1-123
Adv Food Technol Nutr Sci Open J
ISSN 2377-8350
Page 137
metabolites are at high concentrations. At low concentrations,
the metabolites may exert antioxidant effects. The enzymatic
oxidative products of ω-3 and ω-6 PUFAs may have opposing
effects on inammation and cardiac arrhythmicity. At present,
the functions and working mechanisms of PUFA metabolites are
not completely understood. Moreover, whether PUFA itself or
oxidized PUFA metabolites play more important roles in vari-
ous disease context remains unclear. Herein, future studies are
needed to tackle these problems.
CONFLICTS OF INTEREST
The authors declare that they have no conicts of interest.
ACKNOWLEDGMENT
The author would like to acknowledge Dr. Lei Liu, currently
an Assistant Professor in College of Veterinary Medline, Hunan
Agricultural University, China for the helpful comments and
suggestions.
REFERENCES
1. World Health Organization. The world health report: reducing
risks, promoting healthy life. Geneva, Switherland, 2002.
2. Yessoufou A, Nekoua MP, Gbankoto A, Mashalla Y, Moutai-
rou K. Benecial effects of omega-3 polyunsaturated fatty acids
in gestational diabetes: consequences in macrosomia and adult-
hood obesity. Exp Diabetes Res. 2015. 2015: 1-11.
3. Nabavi SF, Bilotto S, Russo GL, et al. Omega-3 polyunsatu-
rated fatty acids and cancer: Lessons learned from clinical tri-
als. Cancer Metastasis Rev. 2015; 34(3): 359-380. doi: 10.1007/
s10555-015-9572-2
4. Khawaja OA, Gaziano JM, Djousse L. N-3 fatty acids for pre-
vention of cardiovascular disease. Curr Atheroscler Rep. 2014;
16(11): 1477S-1482S.
5. van den Elsen L, Garssen J, Willemsen L. Long chain n-3
polyunsaturated fatty acids in the prevention of allergic and car-
diovascular disease. Curr Pharm Design. 2012. 18(16): 2375-
2392.
6. FAO-WHO. Fats and fatty acids in human nutrition: report of
an expert consultation, fao food and nutrition paper #91, FAO,
WHO: Geneva, Switherland, 2010.
7. Harris WS, Mozaffarian D, Rimm E, et al. Omega-6 fatty ac-
ids and risk for cardiovascular disease a science advisory from
the american heart association nutrition subcommittee of the
council on nutrition, physical activity, and metabolism; coun-
cil on cardiovascular nursing; and council on epidemiology and
Figure 1: The oxidation of PUFAs and its impact on food quality and human health. With multiple unsaturated bonds, PUFAs can undergo both non-
enzymatic and enzymatic oxidation and generate a variety of metabolites. Oxidation of PUFAs often brings adverse effects to food by producing off-avors,
reducing food quality and shelf life. The non-enzymatic oxidative products may induce oxidative stress and inammation at high concentrations while
exerting antioxidant effects at low concentrations. The enzymatic oxidative products of ω-3 and ω-6 PUFA may have opposing effects on inammation
and cardiac arrhythmicity.
COX: Cyclooxygenase; CYP: Cytochromes P450; DHA: Docosahexaenoic acid; EPA: Eicosapentaenoic acid; HHE: 4-Hydroxy-2-hexenal; HNE: 4-Hy-
droxy-2-nonenal; LOX: Lipoxygenase; MaR: Maresin; PD/NPD: Protectin/neuroprotectin; PUFA: Polyunsaturated fatty acid; Rv: Resolvin.
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prevention. Circulation. 2009; 119(6): 902-907. doi: 10.1161/
CIRCULATIONAHA.108.191627
8. Weylandt KH, Serini S, Chen YQ, et al. Omega-3 polyunsatu-
rated fatty acids: the way forward in times of mixed evidence.
Biomed Res Int. 2015; 2015: 1-24. doi: 10.1155/2015/143109
9. Gruber F, Ornelas CM, Karner S, et al. Nrf2 deciency causes
lipid oxidation, inammation, and matrix-protease expression
in dha-supplemented and Uva-irradiated skin broblasts. Free
Radic Biol Med. 2015; 88(Pt B): 439-451. doi: 10.1016/j.fre-
eradbiomed.2015.05.006
10. Thomas MJ. Analysis of lipid peroxidation products in health
and disease. In: Spickett CM, Forman H J, eds. Lipid oxidation
in health and disease. Boca Raton: CRC Press, 2015: 137.
11. Pryor WA, Stanley JP. Letter: A suggested mechanism for the
production of malonaldehyde during the autoxidation of polyun-
saturated fatty acids. Nonenzymatic production of prostaglandin
endoperoxides during autoxidation. J Org Chem. 1975; 40(24):
3615-3617.
12. Pryor WA, Porter NA. Suggested mechanisms for the pro-
duction of 4-hydroxy-2-240 nonenal from the autoxidation of
polyunsaturated fatty acids. Free Radic Biol Med. 1990. 8(6):
541-543.
13. Esterbauer H, Benedetti A, Lang J, Fulceri R, Fauler G,
Comporti M. Studies on themechanism of formation of 4-hy-
droxynonenal during microsomal lipid peroxidation. Biochim
Biophys Acta. 1986; 876(1): 154-166. doi: 10.1016/0005-
2760(86)90329-2
14. Esterbauer H, Schaur RJ, Zollner H. Chemistry and bio-
chemistry of 4-246 hydroxynonenal, malonaldehyde and related
aldehydes. Free Radic Biol Med. 1991; 247 11(1): 81-128.
15. Tanaka R, Shigeta K, Sugiura Y, Hatate H, Matsushita T. Ac-
cumulation of hydroxyl lipids and 4-hydroxy-2-hexenal in live
sh infected with sh diseases. Lipids. 2014; 49(4): 385-396.
doi: 10.1007/s11745-013-3875-2
16. Long EK, Picklo MJ, Sr. Trans-4-hydroxy-2-hexenal, a
product of n-3 fatty acid peroxidation: Make some room hne.
Free Radic Biol Med. 2010; 49(1): 1-8. doi: 10.1016/j.freerad-
biomed.2010.03.015
17. Yamada S, Funada T, Shibata N, et al. Protein-bound 4-hy-
droxy-2-hexenal as a marker of oxidized n-3 polyunsaturated
fatty acids. J Lipid Res. 2004; 45(4): 626-634. doi: 10.1194/jlr.
M300376-JLR200
18. Matsushita S, Terao J. Singlet oxygen-initiated photooxi-
dation of unsaturated fatty acid esters and inhibitory effects of
tocopherols and beta-carotene. In: Simic MG, Karel M, eds. Au-
tooxidation in food and biological systems. Springer US, 1980:
27-44.
19. Frankel EN. Lipid oxidation. 2nd ed. Oily Press, 2005.
20. Foote CS. Photosensitized oxidation and singlet-oxygen:
consequences in biological systems. In: Pryor WA, ed. Free radi-
cals in biology. New York: Academic Press, 1976: 85-133.
21. Stratton SP, Liebler DC. Determination of singlet oxygen-
specic versus radical-263 mediated lipid peroxidation in photo-
sensitized oxidation of lipid bilayers: effect of beta-264 carotene
and alpha-tocopherol. Biochemistry. 1997; 36(42): 11-20.
22. Dennis EA, Cao J, Hsu YH, Magrioti V, Kokotos G. Phos-
pholipase A2 enzymes: Physical structure, biological function,
disease implication, chemical inhibition, and therapeutic inter-
vention. Chem Rev. 2011; 111(10): 6130-6185. doi: 10.1021/
cr200085w
23. Smith WL, Urade Y, Jakobsson PJ. Enzymes of the cycloox-
ygenase pathways of prostanoid biosynthesis. Chem Rev. 2011.
111(10): 5821-5865. doi: 10.1021/cr2002992
24. Smith WL, DeWitt DL, Garavito RM. Cyclooxygenases:
structural, cellular, and molecular biology. Annu Rev Biochem.
2000. 69: 145-182. doi: 10.1146/annurev.biochem.69.1.145
25. Joo YC, Oh DK. Lipoxygenases: potential starting biocata-
lysts for the synthesis of signaling compounds. Biotechnol Adv.
2012. 30(6): 1524-1532. doi: 10.1016/j.biotechadv.2012.04.004
26. Isobe Y, Arita M, Iwamoto R, et al. Stereochemical assign-
ment and anti-inammatory properties of the omega-3 lipid
mediator resolvin E3. J Biochem. 2013; 153(4): 355-360. doi:
10.1093/jb/mvs151
27. Serhan CN, Clish CB, Brannon J, Colgan SP, Chiang N,
Gronert K. Novel functional sets of lipid-derived mediators with
antiinammatory actions generated from omega-3 fatty acids
via cyclooxygenase 2-nonsteroidal antiinammatory drugs and
transcellular processing. J Exp Med. 2000; 192(8): 1197-1204.
doi: 10.1084/jem.192.8.1197
28. Arita M, Bianchini F, Aliberti J, et al. Stereochemical assign-
ment, antiinammatory properties, and receptor for the omega-3
lipid mediator resolvin E1. J Exp Med. 2005; 201(5): 713-722.
doi: 10.1084/jem.20042031
29. Serhan CN, Hong S, Gronert K, et al. Resolvins: a family
of bioactive products of omega-3 fatty acid transformation cir-
cuits initiated by aspirin treatment that counter proinammation
signals. J Exp Med. 2002. 196(8): 1025-1037. doi: 10.1084/
jem.20020760
30. Ward PA. Resolvins on the way to resolution. J Exp Med.
Advances in food technology and
nutritional sciences
Open Journal http://dx.doi.org/10.17140/AFTNSOJ-1-123
Adv Food Technol Nutr Sci Open J
ISSN 2377-8350
2015; 212(8): 1142. doi: 10.1084/jem.2128insight4
31. Marcheselli VL, Hong S, Lukiw WJ, et al. Novel doco-
sanoids inhibit brain ischemia- reperfusion-mediated leukocyte
inltration and pro-inammatory gene expression. J Biol Chem.
2003; 278(44): 43807-43817. doi: 10.1074/jbc.M305841200
32. Mukherjee PK, Marcheselli VL, Serhan CN, Bazan NG.
Neuroprotectin D1: A docosahexaenoic acid-derived docosatri-
ene protects human retinal pigment epithelial cells from oxida-
tive stress. Proc Natl Acad Sci USA. 2004; 101(22): 8491-8496.
doi: 10.1073/pnas.0402531101
33. Serhan CN, Gotlinger K, Hong S, et al. Anti-inammatory
actions of neuroprotectin d1/protectin d1 and its natural stereo-
isomers: assignments of dihydroxy-containing docosatrienes.
J Immunol. 2006. 176(3): 1848-1859. doi: 10.4049/ jimmu-
nol.176.3.1848
34. Serhan CN, Yang R, Martinod K, et al. Maresins: novel
macrophage mediators with potent antiinammatory and prore-
solving actions. J Exp Med. 2009; 206(1): 15-23. doi: 10.1084/
jem.20081880
35. Serhan CN, Dalli J, Karamnov S, et al. Macrophage prore-
solving mediator maresin 1 stimulates tissue regeneration and
controls pain. FASEB journal. 2012; 26(4): 1755-1765. doi:
10.1096/fj.11-201442
36. Dalli J, Zhu M, Vlasenko NA, et al. The novel 13s, 14s-ep-
oxy-maresin is converted by human macrophages to maresin 1
(MaR1), inhibits leukotriene A4 hydrolase (LTA4H), and shifts
macrophage phenotype. FASEB journal. 2013; 27(7): 2573-
2583. doi: 10.1096/fj.13-227728
37. Schmitz G, Ecker J. The opposing effects of n-3 and n-6 fatty
acids. Prog Lipid Res. 2008; 47(2): 147-155. doi: 10.1016/j.plip-
res.2007.12.004
38. Fer M, Dreano Y, Lucas D, et al. Metabolism of eicosapen-
taenoic and docosahexaenoic acids by recombinant human cyto-
chromes p450. Arch Biochem Biophys. 2008; 471(2): 116-125.
doi: 10.1016/j.abb.2008.01.002
39. Racine RA, Deckelbaum RJ. Sources of the very-long-chain
unsaturated omega-3 fatty acids: eicosapentaenoic acid and
docosahexaenoic acid. Curr Opin Clin Nutr Metab Care. 2007;
10(2): 123-128. doi: 10.1097/MCO.0b013e3280129652
40. Kris-Etherton PM, Taylor DS, Yu-Poth S, et al. Polyunsatu-
rated fatty acids in the food chain in the United States. Am J Clin
Nutr. 2000; 71(1): 179s-88s.
41. Whelan J, Rust C. Innovative dietary sources of n-3 fatty
acids. Annu Rev Nutr. 2006; 26: 75-103. doi: 10.1146/annurev.
nutr.25.050304.092605
42. Gatrell SK, Kim J, Derksen TJ, O’Neil EV, Lei XG. Creat-
ing omega-3 fatty-acid-enriched chicken using defatted green
microalgal biomass. J Agr Food Chem. 2015; 63(42): 9315-322.
43. Kolakowska A, Bartosz G. Oxidation of food components:
an introduction. In: Bartosz G, ed. Food oxidants and antioxi-
dants: chemical, biological and functional properties. Taylor &
Francis Group, LLC, 2014: 9-10.
44. Let MB, Jacobsen C, Meyer AS. Sensory stability and oxi-
dation of sh oil enriched milk is affected by milk storage tem-
perature and oil quality. Int Dairy J. 2005; 15(2): 173-182. doi:
10.1016/j.idairyj.2004.06.003
45. Kao JW, Hammond EG, White PJ. Volatile compounds
produced during deodorization of soybean oil and their avor
signicance. J Am Oil Chem Soc. 1998; 75(9): 1103-1107. doi:
10.1007/s11746-998-0297-z
46. Min DB, Callison AL, Lee HO. Singlet oxygen oxidation for
2-pentylfuran and 2-329 pentenyfuran formation in soybean oil.
J Food Sci. 2003; 68(4): 1175-1178.
47. Mallia S, Escher F, Dubois S, Schieberle P, Schlichtherle-
Cerny H. Characterizationand quantication of odor-active
compounds in unsaturated fatty acid/conjugated linoleic acid
(UFA/CLA)-enriched butter and in conventional butter during
storage and induced oxidation. J Agr Food Chem. 2009; 57(16):
7464-7672. doi: 10.1021/jf9002158
48. Arab-Tehrany E, Jacquot M, Gaiani C, Imran M, Desobry S,
Linder M. Benecial effects and oxidative stability of omega-3
long-chain polyunsaturated fatty acids. Trends Food Sci Tech.
2012; 25(1): 24-33. doi: 10.1016/j.tifs.2011.12.002
49. Jacobsen C, Hartvigsen K, Lund P, et al. Oxidation in sh-
oil-enriched mayonnaise 1. Assessment of propyl gallate as an
antioxidant by discriminant partial least squares regression anal-
ysis. Eur Food Res Technol. 1999; 210(1): 13-30. doi: 10.1007/
s002170050526
50. Buettner GR. The pecking order of free radicals and anti-
oxidants: Lipid peroxidation, alpha-tocopherol, and ascorbate.
Arch Biochem Biophys. 1993; 300(2): 535-543. doi: 10.1006/
abbi.1993.1074
51. Serfert Y, Drusch S, Schwarz K. Chemical stabilisation of
oils rich in long-chain polyunsaturated fatty acids during ho-
mogenisation, microencapsulation and storage. Food Chem.
2009; 113(4): 1106-1112. doi: 10.1016/j.foodchem.2008.08.079
52. Nielsen JH, Ostdal H, Andersen HJ. The inuence of ascor-
bic acid and uric acid on the oxidative stability of raw and
pasteurized milk. In: Morello MJ, Shahidi F, Ho CT, eds. Free
Page 139
Advances in food technology and
nutritional sciences
Open Journal http://dx.doi.org/10.17140/AFTNSOJ-1-123
Adv Food Technol Nutr Sci Open J
ISSN 2377-8350
radicals in food: Chemistry, nutrition and health effects. Wash-
ington, DC: ACS Symposium Series, American Chemical Soci-
ety, 2002: 126-137.
53. Rupasinghe HPV, Erkan N, Yasmin A. Antioxidant protec-
tion of eicosapentaenoic acid and sh oil oxidation by poly-
phenolic-enriched apple skin extract. J Agr Food Chem. 2010;
58(2): 1233-1239. doi: 10.1021/jf903162k
54. Arruda CS, Garcez WS, Barrera-Arellano D, Block JM. In-
dustrial trial to evaluate the effect of oxygen concentration on
overall quality of rened, bleached, and deodorized soybean oil
in pet bottles. J Am Oil Chem Soc. 2006; 83(9): 797-802. doi:
10.1007/s11746-006-5017-y
55. Larsen H, Tellefsen SBG, Dahl AV. Quality of sour cream
packaged in cups with different light barrier properties measured
by uorescence spectroscopy and sensory analysis. J Food Sci.
2009; 74(8): S345-S350. doi: 10.1111/j.1750-3841.2009.01303.x
56. Rosenfeld ME, Palinski W, Yla-Herttuala S, Butler S, Witz-
tum JL. Distribution of oxidation specic lipid-protein adducts
and apolipoprotein b in atherosclerotic lesions of varying sever-
ity from WHHL rabbits. Arteriosclerosis. 1990; 10(3): 336-349.
doi: 10.1161/01.ATV.10.3.336
57. Palinski W, Yla-Herttuala S, Rosenfeld ME, et al. Antisera
and monoclonal antibodies specic for epitopes generated dur-
ing oxidative modication of low density lipoprotein. Arterio-
sclerosis. 1990. 10(3): 325-335. doi: 10.1161/01.ATV.10.3.325
58. Yoritaka A, Hattori N, Uchida K, Tanaka M, Stadtman ER,
Mizuno Y. Immunohistochemical detection of 4-hydroxynon-
enal protein adducts in parkinson disease. Proc Natl Acad Sci
USA. 1996; 93(7): 2696-2701.
59. Shibata N, Nagai R, Uchida K, et al. Morphological evidence
for lipid peroxidation and protein glycoxidation in spinal cords
from sporadic amyotrophic lateral sclerosis patients. Brain Res.
2001; 917(1): 97-104. doi: 10.1016/S0006-8993(01)02926-2
60. Okamoto K, Toyokuni S, Uchida K, et al. Formation of
8-hydroxy-2’-deoxyguanosine and 4-hydroxy-2-nonenal-modi-
ed proteins in human renal-cell carcinoma. Int J Cancer. 1994;
58(6): 825-859.
61. Zhong H, Yin H. Role of lipid peroxidation derived 4-hy-
droxynonenal (4-HNE) in cancer: Focusing on mitochondria.
Redox Biol. 2015; 4: 193-199. doi: 10.1016/j.redox.2014.12.011
62. Uchida K, Shiraishi M, Naito Y, Torii Y, Nakamura Y, Osawa
T. Activation of stress signaling pathways by the end product of
lipid peroxidation. 4-hydroxy-2-nonenal is a potential inducer
of intracellular peroxide production. J Biol Chem. 1999; 274(4):
2234-2242. doi: 10.1074/jbc.274.4.2234
63. Kondo M, Oya-Ito T, Kumagai T, Osawa T, Uchida K. Cy-
clopentenone prostaglandins as potential inducers of intracellu-
lar oxidative stress. J Biol Chem. 2001; 276(15): 12076-12083.
doi: 10.1074/jbc.M009630200
64. Awada M, Soulage CO, Meynier A, et al. Dietary oxidized
n-3 PUFA induce oxidative stress and inammation: role of in-
testinal absorption of 4-HHE and reactivity in intestinal cells. J
Lipid Res. 2012. 53(10): 2069-2080. doi: 10.1194/jlr.M026179
65. Jenkinson A, Franklin MF, Wahle K, Duthie GG. Dietary
intakes of polyunsaturated fatty acids and indices of oxidative
stress in human volunteers. Eur J Clin Nutr. 1999; 53(7): 523-
528.
66. Fukuda A, Nakamura Y, Ohigashi H, Osawa T, Uchida K.
Cellular response to the redox active lipid peroxidation prod-
ucts: induction of glutathione s-transferase p by 4-hydroxy-
2-nonenal. Biochem Biophys Res Commun. 1997; 236(2): 505-
509. doi: 10.1006/bbrc.1997.6585
67. Tjalkens RB, Luckey SW, Kroll DJ, Petersen DR. Alpha,
beta-unsaturated aldehydes mediate inducible expression of glu-
tathione s-transferase in hepatoma cells through 393 activation
of the antioxidant response element (ARE). Adv Exp Med Biol.
1999; 463: 123-131.
68. Anderson EJ, Thayne K, Harris M, Carraway K, Shaikh SR.
Aldehyde stress and up-regulation of Nrf2-mediated antioxidant
systems accompany functional adaptations in cardiac mitochon-
dria from mice fed n-3 polyunsaturated fatty acids. Biochem J.
2012; 441(1): 359-366. doi: 10.1042/BJ20110626
69. Anderson EJ, Taylor DA. Stressing the heart of the matter:
re-thinking the mechanisms underlying therapeutic effects of
n-3 polyunsaturated fatty acids. F1000 medicine reports. 2012;
4: 13. doi: 10.3410/M4-13
70. Zhang Y, Sano M, Shinmura K, et al. 4-hydroxy-2-nonenal
protects against cardiac ischemia-reperfusion injury via the
Nrf2-dependent pathway. J Mol Cell Cardiol. 2010; 49(4): 576-
586. doi: 10.1016/j.yjmcc.2010.05.011
71. Isobe Y, Arita M. Identication of novel omega-3 fatty acid-
derived bioactive metabolites based on a targeted lipidomics ap-
proach. J Clin Biochem Nutr. 2014; 55(2): 79-84.
72. Hong S, Lu Y. Omega-3 fatty acid-derived resolvins and
protectins in inammation resolution and leukocyte functions:
targeting novel lipid mediator pathways in mitigation of acute
kidney injury. Front Immunol. 2013; 4: 13. doi: 10.3389/m-
mu.2013.00013
73. Chiang N, Dalli J, Colas RA, Serhan CN. Identication of re-
solvin D2 receptor mediating resolution of infections and organ
protection. J Exp Med. 2015; 212(8): 1203-1217. doi: 10.1084/
Page 140
Advances in food technology and
nutritional sciences
Open Journal http://dx.doi.org/10.17140/AFTNSOJ-1-123
Adv Food Technol Nutr Sci Open J
ISSN 2377-8350
jem.20150225
74. Deng B, Wang CW, Arnardottir HH, et al. Maresin biosyn-
thesis and identication of maresin 2, a new anti-inammatory
and pro-resolving mediator from human macrophages. PLoS
One. 2014; 9(7): e102362. doi: 10.1371/journal.pone.0102362
75. Bagga D, Wang L, Farias-Eisner R, Glaspy JA, Reddy ST.
Differential effects of prostaglandin derived from omega-6 and
omega-3 polyunsaturated fatty acids on COX-2 expression and
IL-6 secretion. Proc Natl Acad Sci USA. 2003; 100(4): 1751-
1756. doi: 10.1073/pnas.0334211100
Page 141