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ASTAXANTHIN : A PROMISING ANTIOXIDANT TO AMELIORATE HEAT STRESS AND IMPROVE PRODUCTION POTENTIAL IN ANIMALS

Authors:
ASTAXANTHIN : A PROMISING ANTIOXIDANT TO AMELIORATE HEAT
STRESS AND IMPROVE PRODUCTION POTENTIAL IN ANIMALS
Susmita Majumder, Lata Kant, Priyanka M. Kittur, Pravasini Das, Poonam Yadav, H. A. Samad, V. S.
Chouhan, Gyanendra Singh and V. P. Maurya*
Division of Physiology and Climatology, ICAR-Indian Veterinary Reasearch Institute, Izatnagar, Bareilly - 243 112, India.
Corresponding author - V P Maurya, *e-mail : vpmaurya@rediffmail.com
(Received 4 October 2023, Revised 18 November 2023, Accepted 30 November 2023)
ABSTRACT : A carotenoid, astaxanthin is extensively distributed in microbes and marine species. At the upcoming time,
astaxanthin will have the most share of the worldwide carotenoids market due to its widespread application in animal feed,
cosmetics and nutraceuticals. Because of its distinct molecular makeup, astaxanthin has strong antioxidant properties and may
be useful in biochemical research. We now have a better knowledge of how esterification and isomerization contribute to the
structure-function connection of dietary astaxanthin thanks to recent studies. Astaxanthin (AST) is a red carotenoid pigment
that is used in food, animal feed, cosmetics, medicine, and nutraceuticals. Fish, crustaceans, algae, and birds that are naturally
occurring all contain astaxanthin, mostly in the form of fatty acid esters. Numerous studies have shown that astaxanthin has
positive effects when used as a medicinal agent in animal diet. Numerous important biological effects of astaxanthin include
antihypertensive, antioxidant, anti-obesity and anti-carcinogenic characteristics. As a potent immunomodulator to preserve the
health and wellbeing of both people and animals, astaxanthin has lately grown in popularity. Astaxanthin is widely used in the
production purpose in animal as well as in medical sciences. Understanding the structure, origin and mode of action of
astaxanthin in the body offers a theoretical foundation for its therapeutic use and might improve the screening of substances
linked to the treatment of numerous disorders. With a focus on practical applications, this review article tries to make clear
astaxanthin’s key characteristics, including its bioavailability, therapeutic effects and synthesis. It is anticipated that knowledge
of these advantages and production would help the livestock sector create nutritional programmes that guarantee the protection
of animal health.
Key words : Astaxanthin, antioxidant, heat stress,
How to cite : Susmita Majumder, Lata Kant, Priyanka M. Kittur, Pravasini Das, Poonam Yadav, H. A. Samad, V. S. Chouhan,
Gyanendra Singh and V. P. Maurya (2024) Astaxanthin : A promising antioxidant to ameliorate heat stress and improve production
potential in animals. J. Exp. Zool. India 27, 000-000. DOI: https://doi.org/10.59467/jez.2024.27.000
J. Exp. Zool. India Vol. 27, No. 1, pp. 000-000, 2024 ISSN 0972-0030
DocID: https://connectjournals.com/03895.2024.27.000 eISSN 0976-1780
DOI: https://doi.org/10.59467/jez.2024.27.000
INTRODUCTION
A group of carotenoids known as xanthophylls, which
principally consists of lutein, zeaxanthin, β-cryptoxanthin,
and canthaxanthin, also contains astaxanthin (AST), an
oxygenated carotenoid (Jackson et al, 2008). This
substance naturally exists in several different living things,
such as microalgae and plants, but it is particularly
prevalent in the aquatic environment as a reddish-orange
pigment present in a variety of marine species (Ambati
et al, 2014). Phytoplankton and marine bacteria produce
AST, which is subsequently transferred to fish through
the food chain. However, the AST feed supplement gives
fish raised in aquaculture (like farmed salmonids) the
distinctive pink colour to their flesh (Lim et al, 2018).
Although, AST was first used as an animal food additive,
the US Food and Drug Administration (FDA) allowed its
use as a dietary supplement, when the first biological
activity were revealed and following a thorough
examination of its safety profile (Guerin et al, 2003). Grand
View Research projected that the astaxanthin market was
worth USD 1 billion globally in 2019. Due to growing
public knowledge of natural astaxanthin and its well-
established, multifaceted health advantages and safety, it
is predicted to increase at a compound yearly growth rate
of 16.2% and reach USD 3398.8 million from 2019 to
2027.
Chemical structure of astaxanthin
As with the majority of carotenoids, astaxanthin is a
tetraterpene with 40 carbons made up of connected
isoprene units. Two terminal rings and a linear polyene
Susmita Majumder et al
chain make up astaxanthin’s molecular structure.
Astaxanthin’s pink and red colour and anti-oxidative
capabilities are both attributed to its system of 11
conjugated double bonds. In addition, each of
astaxanthin’s terminal rings has two polar function groups:
hydroxyl (OH) at the two asymmetric carbons C3 and
C3 and keto (=O) at the carbons C4 in the molecule.
Astaxanthin is distinct from other carotenoids because
of the existence of these groups, which are characteristic
to it (Stachowiak, 2021). Due to its capacity to neutralize
free radicals, astaxanthin has a diverse array of
applications in the food, feed, cosmetic, aquaculture,
nutraceutical and pharmaceutical sectors (Shah et al,
2016).
Source of astaxanthin
Algae, salmon, trout, prawns, krill, yeast and crayfish
are astaxanthin’s natural food sources. Haematococcus
pluvialis, Chlorella zofingiensis, Xanthophyllomyces
dendrorhous, Catenella repens and Agrobacterium
aurantiacum are some of the microorganisms that
produce astaxanthin. The major sources of commercial
astaxanthin are Haematococcus, Phaffia yeast and
chemical synthesis. One of the greatest natural sources
of astaxanthin is Haematococcus pluvialis (Ambati et
al, 2014). As a lipophilic substance, astaxanthin may be
dissolved in oils and solvents. Astaxanthin is extracted
using solvents, acids, edible oils, microwave assistance,
and enzymatic processes. In Haematococcus encysted
cells astaxanthin builds up. Haematococcus astaxanthin
was extracted using a variety of acid treatments, with
hydrochloric acid recovering up to 80% of the pigment
(Sarada et al, 2006). 70% of the astaxanthin was
recovered from encysted cells after they had been
exposed to 40% acetone at 80°C for two minutes,
kitalase, cellulose, abalone, and acetone powder. When
hydrochloric acid was treated using sonication for 15 and
30 minutes at various temperatures, a high astaxanthin
output was seen (Mendes-Pinto et al, 2001).
The majority of microalgal strains utilised to produce
astaxanthin, including Chlorella zofingiensis and
Haematococcus pluvialis, are members of the
Chlorophyta. Typically, these green microalgae do not
undergo significant morphological changes while being
grown (Ranjbar et al, 2008). The resting cysts, which
are primarily give the microalgae their blood-red colour
and astaxanthin concentration, are created when the
microalgae cells are exposed to certain unfavourable
circumstances (Kobayashi, 2003). Microalgal
development is limited during the resting cyst stage, but
the ability of algal cells to survive in a hostile environment
will rise (Ranjbar et al, 2008). As a result, certain
microalgal strains produce astaxanthin as a kind of self-
defense that enhances algal cell survival at the price of
biomass accumulation in unfavourable environmental
circumstances. There are two different processes at work
when astaxanthin is accumulated from microalgae.
Mechanism of action of astaxanthin
Conjugated double bonds, hydroxyl, and keto groups
are all present in astaxanthin. It possesses both hydrophilic
and lipophilic qualities (Higuera-Ciapara et al, 2006).
Conjugated double bonds at the compound’s centre are
what give it its red colour. By giving electrons to free
radicals and interacting with them to create a more stable
product and stop free radical chain reactions in a range
of living creatures, this form of conjugated double bond
functions as a potent antioxidant (Guerin et al, 2003).
Astaxanthin showed more biological activity than other
antioxidants due to its capacity to create an internal-
external connection with cell membrane (Ambati et al,
2014). With polar structures—ionone rings—at both ends,
the conjugated double bond system in the middle of
astaxanthin’s structure creates a non-polar area with a
potent oxidant-suppressing effect. Astaxanthin’s polyene
long chain and ionone rings both have the capacity to
scavenge free radicals. The ionone rings at both ends of
the molecule serve a functional purpose because
Fig. 1 : Two modes of astaxanthin production (Lu et al, 2021).
Astaxanthin as a promising antioxidant to ameliorate heat stress and improve productuction potential in animals
astaxanthin molecules are more polar and have better
membrane function due to the presence of both hydroxyl
and ketone groups (Liu et al, 2022). In animals, natural
astaxanthin may pass the blood-brain barrier and exert
its antioxidant effects outside of blood-brain barrier. As
a result, astaxanthin can lessen the impact of neurological
illnesses like Alzheimers and others. According to Nagata
et al (2006), astaxanthin can improve the respiratory and
sympathetic nervous systems’ performance and inhibit
the formation of fibrosarcoma, breast, prostate and
embryonic fibroblasts (Palozza et al, 2009), cell death,
cell proliferation and mammary tumour (Nakao et al,
2010). Due to its unique chemical composition, AST has
a strong antioxidant impact that shields the entire cell.
AST might control reduced glutathione and SOD (Super
oxide dismutase) to improve the body’s endogenous
antioxidant defence system and direct elimination of free
radicals and ROS. It can also manage body cholesterol
levels and levels of T and B lymphocytes (Pertiwi et al,
2022).
Potency of asataxanthin
Singlet oxygen quenching power
Astaxanthin
540 times stronger than vitamin E
40 times greater capacity than carotenoids
6000 times stonger than vitamin C
3000 times stronger than reveratol
800 times stronger than CoQ 10
[Nishida et al (2007), Zhu et al (2021), Vitacare biotechnology]
Bioavailability of astaxanthin
In recent decades, the fields of food and medicine
have seen a rise in interest in bioavailability and bio-
accessibility. Because the solubility of bioactive
compounds dictates their bioavailability, nutrient functional
lipid molecules’ delayed dissolution or solubilisation in
aqueous based systems results in their poor absorption
rate and as a result, their low bioavailability (Anarjan et
al, 2012). Carotenoids, which are extremely lipophilic
chemicals, have a limited bioavailability. Carotinoids’ low
bioavailability is likely due to difficulties with their
breakdown in gastrointestinal fluids. A saturated capacity
of integration into bile micelles, which are generated
during lipolysis and aid in the absorption of lipophilic
substances is another mechanism that has been proposed
to restrict absorption. Conjugated bile salt’s presence and
capacity to form bile salt micelles are regarded to be the
primary causes of the increased bioavailability of
carotenoids following co-administration of fat (Odeberg
et al, 2003). Several different digestive enzymes help
astaxanthin, a carotenoid, to be liberated from the food
matrix and subsequently disseminated and dissolved
(Reboul, 2019). Then, in order to create mixed micelles,
astaxanthin is emulsified and combined with lipids (such
as cholesterol and phospholipids), by-products of lipid
digestion (such as free fatty acids and lysophospholipids)
and bile salts. When astaxanthin dissolves in mixed
micelles, tiny intestinal epithelial cells take it up and pack
it into chylomicrons, which are then secreted into the
lymphatic system, where they take part in blood circulation
and are then dispersed to various tissues (Liu et al, 2022).
Astaxanthin comes from two different sources: synthetic
biology and biological acquisition (Higuera-Ciapara et al,
2006). The bioavailability of synthesised astaxanthin,
which has a cis-structure, is quite poor. The trans-
structure of natural astaxanthin possesses biological
action and is comparatively stable (Zhu et al, 2021).
Antioxidant activity of astaxanthin
Due to the crucial functions of scavenging free
radicals and reducing the radical-induced destruction of
live cells or tissues, antioxidants are necessary for diets
and cosmetics. According to Tseng et al (2020), an
antioxidant is a chemical that has the ability to remove
free radicals from a system by either interacting with
them to produce innocuous products or by stopping
oxidation reactions. MDA levels, protein oxidation product
(APOP), cortical nitric oxide (NO), hypothalamus,
hippocampus, striatum and cerebellum dramatically
decrease in treated rats after astaxanthin administration.
While raising the quantity of GSH in the brain, astaxanthin
greatly boosts the activity of the CAT and SOD enzymes
(Zhang et al, 2017). By promoting mitochondrial
biogenesis and preserving mitochondrial integrity,
astaxanthin protected the mouse’s skeletal muscle against
the oxidative damage brought on by heat stress (Ambati
et al, 2014).
Application of astaxanthin in animal
Animals are administered astaxanthin as a feed
ingredient to boost output and reduce heat stress. Due to
its role in illness conditions, it is mainly utilized for
therapeutic purposes in humans. Numerous studies on
astaxanthin are being conducted on both humans and
animals. In this review, we will try to highlight some
research work of Astaxanthin in animal as well as human
also. The positive effects of daily dietary astaxanthin at
0.25 mg/kg body weight on the weight, feed efficiency,
Bcl-2 (B-cell lymphoma 2), adipose leptin hormone and
lowered skin temperature, plasma cortisol, interleukins,
nuclear factor-kappa B (NF-κB) and caspase-3
expression patterns of Karan Fries heifers were reported
Susmita Majumder et al
by Kumar and Singh (2019). Similarly, in the Egyptian
buffalo, astaxanthin supplementation raised glucose levels
while lowering non-esterified fatty acid levels, plasma
prolactin and respiration rate (Carballo et al, 2019).
According to Zenteno-Savýìn et al (2002), introducing
astaxanthin (6 mg/day) to a milk substitute for newborn
lambs improved the quality of meat by increasing the
redness of meat and fat, lipid stability and lowering the
buildup of butylated hydroxytoluene (BHT) in meat.
Prinyanka, 2022 found that giving goats’ astaxanthin has
a positive impact on their physiological, biochemical and
hormonal alterations during heat stress condition.
According to Soren et al (2017), the use of TEYCAF
extender improved the quality of sperm during
preservation at 5°C (refrigerator temperature). The
prolonged semen’s reduced quantity of SOD and CAT
further suggests that astaxanthin has antioxidant
properties. Additionally, Fang et al (2015) and Farzan et
al (2014) showed that supplementing ram and bull
prolonged semen with astaxanthin reduced
malondialdehyde and reactive oxygen species (ROS) and
improved the quality of the sperm throughout the 72-hour
storage period at 5°C. After being ingested by animals,
astaxanthin may be directly retained in tissues without
alteration or metabolic change (Lim et al, 2018), which
gives certain animals’ skin and eggs a healthy golden
yellow or red appearance. However, the amount egg
polyunsaturated fatty acids in the yolk might influence its
colour, and laying hens’ diets could be supplemented with
microalgal astaxanthin to enhance it (Zhu et al, 2021).
The milk output was increased by 5.39, 13.8 and 15.6%,
respectively, above the control group, when astaxanthin,
prill fat, and their combination were added to Groups II
(astaxanthin), III (prill fat), and VI (astaxanthin + prill
fat). Comparing the combination group to the control and
other treatment groups, there was an improvement in
immunity and a drop-in stress levels in addition to the
combination group’s higher milk output (Somagond et al,
2022). When added to food for 6 weeks in the case of
healthy dogs and 8 weeks in the case of obese dogs,
astaxanthin successfully stimulated antioxidant and liver
function, which was then followed by improved lipid
metabolism (Murai et al, 2019). By lowering the
expression of heat shock proteins, astaxanthin may
enhance grill performance. It also enhances the quality
of chicken meat and eggs (Pertiwi et al, 2022). Gao et al
(2020) found that AST supplementation in a grill diet
decreased the hepatic mRNA levels of several redox
status-controlling genes, including heat shock protein 70
(HSP70), heat shock transcription factor 1 (HSTF1), c-
Jun N-terminal kinase 1 (JNK1), tumour necrosis factor-
a and sterol regulatory element-binding protein 1.
Malondialdehyde (MDA) levels in the leg muscles
decreased as a result of dietary ASTA, while plasma
levels of catalase and superoxide dismutase increased
linearly. The addition of astaxanthin to the grill meal also
raised the levels of total antioxidant potential, 2,2-diphenyl-
1-picrylhydrazyl radical scavenging, and 3-
ethylbenzothiazoline-6-sulfonate reduction activity in the
leg muscle (Kumar et al, 2019). Heifers were given
astaxanthin in their diets at a rate of 0.25 mg/kg of body
weight each day and compared to a control diet, high
ambient temperature increased body weight, FCR, and
leptin hormone levels while lowering skin temperature
(Kumar and Singh, 2019). Carballo et al (2019) reported
that buffaloes given prill fat at 100 g/animal/day along
with astaxanthin at 0.25 mg/kg body weight per day
showed reductions in non-esterified fatty acids in plasma,
elevated glucose, decreased prolactin and decreased
respiration rate. When astaxanthin (6 mg/day) was given
Fig. 2 : Transmembrane antioxidation of astaxanthin (Liu et al, 2022).
Astaxanthin as a promising antioxidant to ameliorate heat stress and improve productuction potential in animals
to newborn lambs, the amount of BHT (Butylated
hydroxytoluene) that accumulated in the flesh reduced,
the colour of the meat and fat rose, and the stability of
the lipid in frozen meat increased (Zenteno-Savýn et al,
2002). In training Thoroughbred horses, Sato et al (2015)
found that continuous dietary supplementation with
astaxanthin and L-carnitine decreased serum Creatine
kinase and Lactate dehydrogenase isoenzyme-5(LDH-
5) activity levels and delayed the onset of clinical signs
of exertional rhabdomyolysis. Inoue et al (2019) reported
that in rooster sperm, astaxanthin and cadmium
nanoparticles protected against lipid peroxidation and
improved the enzymatic (MDA, CAT, SOD, TAC and
GPX) antioxidant systems. The findings show that at 25
mg/kg, astaxanthin nanoparticles can function as a potent
antioxidant to shield rooster testes from oxidative stress
caused by cadmium (Inoue et al, 2019). In case of human,
Patients with functional dyspepsia were given a single
dosage of 100 mg astaxanthin and a daily dose of 40 mg
for four weeks (Kupcinskas et al, 2008), a daily dose of
4 mg for 12 months in mascular degeneration patients
did not result in any negative side effects (Yang et al,
2013).
CONCLUSION
The link between astaxanthin structure and function
as well as astaxanthin metabolism have made significant
progress in recent years. The bioavailability and biological
activity of astaxanthin are influenced by isomerization
and esterification. The distinctions in the contributions of
various astaxanthin isomers to health benefits are a
fascinating area for in-depth research, in addition to
variances in the possible selective absorption and
isomerization of astaxanthin. There are several animal
health and production procedures where astaxanthin is
advantageous. Astaxanthin is a safe, pleiotropic drug
without significant harmful effects. Astaxanthin given
orally or intravenously has been proven to reduce heat
stress, increase milk production in buffalos, have anti-
inflammatory effects, and promote the activity of
antioxidant enzymes. It is anticipated that study into the
biological role of the catabolites created by dietary
astaxanthin during absorption and metabolism will be a
fruitful field in the near future. More reliable data in
humans is urgently required in addition to pilot studies
done in animals in vitro to evaluate the practical
advantages of astaxanthin and eventually provide
optimised dietary intake recommendations.
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