Aflatoxins, as well as
ochratoxin generally are some of the groups of mycotoxins. Mycotoxins can be
describes as toxic microorganisms that can be directly taken by human or
animals via food, which can cause danger towards humans’ as well as animals’
health (Basappa, 2009). This has clearly showed that both aflatoxin and
mycotoxins has been among some compounds, or microorganisms that contain toxic,
as well as carcinogenic properties towards humans’ and animals body system.
These toxic compounds can be found in some of the food taken by humans and also
animals, and eventually can be ingested thoroughly by them. As a result of this
ingestion of toxic compunds, this can give some effects on humans’ and animals’
body systems as those compounds can harm the cell, organs and so on. As a
result, the health of infected organisms will be in great danger if those
mycotoxin-containing foods are taken by them, especially in very huge quantity.
However, if those kinds of foods have only be taken in small amount, this might
not give any significant effects towards humans’ and animals’ health.
Aflatoxins generally were “mycotoxins that are produced
by various Aspergillus species including A.
flavus, A.parasiticus and A.nominus.”
(Chen, Grenier & Applegate, 2013). Other than that, Basappa (2009) has
defined aflatoxins as a set of secondary metabolite compounds which has very
high toxic as well as carcinogenic properties, produces by some species such as
Aspergillus flavus and A.parasiticus. This has meant that aflatoxins
are the products of secondary metabolites that mainly forms from aspergillius
species of plant, which shows that aflatoxins are originated from plant
species. Furthermore, those aflatoxins that formed has their main
characteristics in which those compounds are very toxic and has carcinogenic
properties, thus these aflatoxins might cause cancer towards infected
organisms. Hence, these aflatoxins can be describes as “danger” if taken by
organisms, mainly in excessive manner. The examples of plants that contained
aflatoxins are maize, some beans and so on.
Meanwhile, ochratoxins, which also parts of mycotoxins,
can be describes as “mycotoxin found as a contaminant in different food
matrices such as cereals, beans, dried fruits and beverages such as beer, wine
and coffee. This mycotoxin is a secondary metabolite produced by several mould
species of Aspergillus and Penicillium” (Vanesa & Ana, 2012). Basically,
like the aflatoxins, ochratoxins can also be found as ingredients in some kind
of food as mentioned before, which are, for example, cereals, dried fruits, and
beans. In addition, those ochratoxins can also been found in some kind of
beverages especially in beers, wines and some kinds of coffees. Likewise of
those aflatoxins compound, ochratoxins also may harm humans’ as well as animals’
health if those ochratoxin-containing foods and beverages have been taken
excessively. This is because, as ochratoxins that are also parts of mycotoxins,
these compounds are believed to give toxic and some carcinogenic properties
towards the humans or animals that consume food or beverages containing these
compounds.
In this topic “Aflatoxins and Ochratoxins”, first of all,
this topic will begin with discussion about the general information about both
aflatoxins and ochratoxins. This general information will overview some
characteristics of aflatoxins and ochratoxins. This will include the structure,
the properties (physical, chemical, toxicology), how to distinguish both
compounds and many more. Then, the classifications of aflatoxins and
ochratoxins will be discussed in detail, as there are a lot of classifications
regarding both types of compounds, for example, Aflatoxin B1, Ochratoxin A and
many more. Subsequently, general ideas on both aflatoxins and ochratoxins
synthesis will be discussed. Lastly, some examples of health risks/problems
that has been caused by both aflatoxins and ochratoxins wil be discussed. For
example, effect of aflatoxins on maize production, ochratoxins in coffee and
their health risks on human, effects of aflatoxins on poultry production and
many more.
Aflatoxins, as
mentioned earlier, are secomdary metabolites produced by some plant species
namely Aspergillius flavus and A.
parasiticus. Those metabolites formed generally contained high toxic and
carcinogenic properties towards humans and animals. Furthermore, as these
aflatoxins has been studied to give some teratogenic and mutagenic effects in
some experimental animals” (Basappa, 2009), these has shown further effects
that can be happened towards animals and humans regarding aflatoxins, such as
some cancer, birth defects, mutations and many more. Generally, those toxins
that have been contained in the aflatoxins can be simply detected using UV
spectrophotometry analysis, and those differences of toxin compounds that has
been found in aflatoxins gave the different classifications of aflatoxins such
as aflatoxin B1, aflatoxin B2, aflatoxin G1, aflatoxin G2 and so on.
From the general
structure, it can be studied that the difuranucoumarin is the main, or in the
other word, the backbone structure of the aflatoxins. Meanwhile, the final part
of the general aflatoxin compound is the part that gives different classifications
of the aflatoxins. In fact, those parts that show aflatoxins classifications is
the part whereby the toxic properties are often found.
For the properties of aflatoxins, generally, for
toxicology properties, those aflatoxins have toxins structure that can give
harmful properties such as carcinogenic, mutagenic, teratogenic and many more.
However, according to Basappa (2009) and Morteza Azizollahi Aliabadi, Fatemeh
(Elham) Alikhani, Mahya Mohammadi and Reza Kazemi Darsanaki (2013), there are
some of the classifications of those aflatoxins which are non-toxic, and this
non-toxic aflatoxins can be used as treatment and biological control of those
aflatoxin-caused health effects.
For
chemical properties of aflatoxins, generally, aflatoxins are highly oxygenated
compounds. This is due to the large amount of oxygen compounds in the aflatoxin
structures. This oxygen in aflatoxins are highly reactive and can undergo redox
reaction very easily with humans’ or animals’ body systems if taken, which can
cause effect on the chemical compositions in humans’ or animals’ body systems,
hence, cause harm towards their health. Furthermore, aflatoxins are
heterocyclic compounds, led by coumarin nucleus and surrounded by bifuran, as
well as pentanone/lactone structure. All those structures have given
significant towards biological functions of aflatoxins as well as their
toxicology functions.
Meanwhile, for
ochratoxins, as differed from those aflatoxins which are secondary metabolites,
instead, are contaminants that formed in food, for example, cereals, beans,
dried fruits, and also in beverages such as beer, wine and coffee. This has
meant that as differed from aflatoxins which are secondary metabolites that
readily produced by some of the plant species, these ochratoxins are
contaminants that has been resulted to be formed by some food and beverages. In
short, ochratoxins has only been formed of the food or beverages that have been
contaminated by environmental factors.
Generally, the structure
of ochratoxins is based of para-chlorophenol methyl dihydroisocoumarin as
parent compound. Then, there were derivatives of amide link of L-phenylalanine at
ortho position of the para-chlorophenol parent structure. That structure is
generally derived from combinations of coumarin group with para-chorophenol as
well as the amide linkage of L-phenylalanine directly to the
para-chlorophenolic group. This ochratoxin structure is generally derived from
shikimic acid pathway between phenylalanine and malonyl-CoA synthesis of coumarin
structure, as well as formation of para-chlorophenolic group and amide linkage
to the phenylalanine group. These ochratoxins formed are not the main product
of the shikimate pathway phenylalanine and malonyl-CoA synthesis of coumarin
derivative structures, however, has been produced as contaminants of both
phenylalanine and coumarin reaction schemes.
For the toxicology properties of this ochratoxin groups,
the most notable toxic properties has come from the classification of
ochratoxin A. This ochratoxin group has been found mainly in beverages such as
beers and mainly in comtaminated coffee samples. Those ochratoxins, which are
known as most toxic among ochratoxin groups, has been generally can cause
highly damage towards human health. This is because, this ochratoxin A contain
dangerous toxicity such as neurotoxins as well as hepatotoxins which can highly
affected the neurotransmitter and digestive organs such as liver, gallbladder,
pancrease and many more. This can cause huge damage towards human health as
neurotransmitter system and digestive system are among the most important human
body systems. Therefore, it is very important to ensure that ochratoxins
contaminated in the coffee/any beverage samples needed to be isolated and
cleaned until the safe level of “5 mg/kg
for roasted coffee beans and ground roasted coffee, and 10 mg/kg for soluble
coffee” (Vanesa,& Ana, 2012) has been achieved.
For physical properties of ochratoxins, generally, these
ochratoxins are mainly polar; therefore these ochratoxins can be easily
absorbed in our body systems throughout water. Furthermore, the ochratoxins are
very permeable towards organ membrane, resulting to easy diffusion towards
targeted body systems, or body organs. Next, for chemical properties of the
ochtaroxins, as there are a lot of functional groups existed on the structure,
this has shown that thess ochratoxins are highly reactive, and a lot of
chemical reaction can be derived from this compound. This is the factor that is
believed to give toxicological properties towards this ochratoxin compound.
To proceed, there are
several differences between aflatoxins and ochratoxins. Firstly, aflatoxins are
the secondary metabolite products that are derived from difuranucoumarins,
while ochratoxins are contaminants of phenylalanine’ and coumarin’s shikimic acid
reaction schemes. Then, the aflatoxins has given toxicological properties of
mainly carcinogenic, mutagenic and teratogenic properties, while ochratoxins
give more vastly toxicological properties such as neurotoxic, hepatotoxic,
carcinogenic, and many more. In short, ochratoxins are generally more toxic
than aflatoxins, as ochratoxins can cause more severe diseases toward humans
and animals.
Other than that, aflatoxins are mainly found in plants
such as Aspergillius flavus and A.
parasiticus. Meanwhile, ochratoxins generally can be found in in food, for
example, cereals, beans, dried fruits, and also in beverages such as beer, wine
and coffee. To continue, ochratoxins have higher reactivity than aflatoxins as
ochratoxins contains more functional groups than aflatoxins. Last but not
least, not all aflatoxins have contained toxicological properties as there are
non-toxic aflatoxins, and ochratoxins are completely considered as highly toxic
compounds.
For the similarities between aflatoxins and ochratoxins,
first of all, both of aflatoxins and ochratoxins have contained toxicological
properties, in general. Other than that, both aflatoxins and ochratoxins
contained various classifications according to the structures and properties.
Other than that, both can harm humans’ and animals’ health. Subsequently, both
contained coumarin-derived structures, and both originated via shikimate
pathway. Lastly, both aflatoxins and ochratoxins may not give toxicological
effects if both have been taken in very small amounts inside the body systems.
For structural classifications of aflatoxins, first of all, the
aflatoxin B1, which is the most toxic and carcinogenic aflatoxin, contain
mostly unsaturated structure. In addition, there are no hydroxyl groups that
can be found in this aflatoxin B1 structure. Then, the other classification is
aflatoxin B2. This aflatoxin B2, accoding to Basappa (2009), has been derived
from aflatoxin B1. This has been formed via incubation of aflatoxin B1 with
hydrogenation reaction that occurred at aflatoxin B1 structure, hence make
aflatoxin B2 to be also known as dihydroaflatoxin B1 which is less toxic than
the aflatoxin B1 origin.
Then, for aflatoxin G1, this type of aflatoxin shares a
lot of similarities with aflatoxin B1; only slight difference is that this
aflatoxin G1 might contain hydroxyl group in the structure, which cannot be
found in the aflatoxin B1 structure. Meanwhile, the aflatoxin G2, likewise
aflatoxin B2, is the derivative of aflatoxin G1 which also can be known as
dihydroaflatoxin G1. For the toxicological properties, both aflatoxin G1 and
aflatoxin G2 are less toxic that their respective aflatoxin B1 and aflatoxin
B2.
Subsequently, from those four main classifications of
aflatoxins, there are lot aflatoxin metabolites and derivatives can be formed
from those structures. These have included aflatoxins M1, M2, GM1 and GM2,
aflatoxin B2a and G2a, aflatoxin M2a and GM2a, aflatoxin Q1, aflatoxin P1,
aflatoxin B3 which also known as parasiticol, aflatoxin R0 (Aflatoxicol),
aflatoxicol H1, aflatoxicol M1, reduced aflatoxin B1 and B2, aflatoxin B1-2-3-oxide,
and lastly, O-alkyl aflatoxin.
Among
the most notable aflatoxin derivatives is aflatoxin B2a which is generally not
active, or non-toxic. Other than that, aflatoxin P1 has been noted to become
non-toxic when exposed to chicken embryo. Moreover, aflatoxin P1 (parasiticol)
is among the least toxic among the toxic aflatoxin derivatives, found in
poultry productions. In addition, aflatoxin R0 (aflatoxicol) can be highly
discovered in bird, rabbit, fish, rodents and livestock, containing plunge
mutagenic properties. Lastly, the O-alkyl aflatoxin “has been identified as major
adduct formed between aflatoxin B1 and DNA or RNA” (Basappa, 2009).
There are some classifications regarding
ochratoxins, which regarding to the source of the ochratoxin compounds.
However, as highly opposed to aflatoxins which has a lot of discovered categories
and derivatives, there are only one most significant ochratoxin group which has
been discovered until now, which is known as Ochratoxin A (OTA). This OTA is
originated from
Aspergillus species.
According to Reddy and
Bhoola (2010), this OTA can stay within a very long time in human bodies,
mostly found in serum sample. As a result, this OTA can stay in a very long
time in the human bodies; hence can cause severe effects towards human health.
In fact, OTA is among the most toxic yet dangerous mycotoxin. This is because;
this OTA contains a lot of human health toxins, such as neurotoxins,
hepatotoxins, nephrotoxic. This has resulted on various important body system
defects, which includes neurotransmitter, digestion systems, secretory systems
and many more. In short, this OTA can cause severe diseases towards human
bodies as well as animals.
Unfortunately, until now, the other
classifications of ochratoxins are still cannot be discovered. There is
research about ochratoxins in pennicilium
species, however, the research about the types of ochratoxin contained is still
yet ongoing.
The synthesis of
Aflatoxin B1 begins with Wittig-carboxymetyl addition reaction on
coumarin enoate ester structure, forming enal. Then, the enal undergoes allylic
oxidation, resulting formation of new enal enoate ester. After that, conjugated
reduction occurred, and difuranocoumarin begin to form.
After
the difuranocoumarin formation, acetylation of OBn occurred, to be replaced
with OAc functional group. After that, Penchmann reduction occurred, followed
by formation of methyl dihydroisodifuranocoumarin (with formation of new
six-membered ring ester). After the formation, hydration occurs, forming
carboxylic acid group. Then, Friedel-craft acylation occurs, forming new
five-membered ring ketone. Before the formation of the aflatoxin, reduction has
occurred, lactone turns to lactol, followed by ester pyrolysis, resulting the
formation of desired aflatoxin B1 product.
As compared to the
synthesis of the aflatoxins, ochratoxins are not the secondary metabolite,
instead just contaminants of phenylalanine reacted with coumarin derivatives,
thus the synthesis of this particular ochratoxin compound is much simpler compared
to aflatoxins synthesis.
The synthesis begins with formation of malonyl-CoA from
the polyketide synthase of acetyl-CoA and malonate. Then the malonyl-CoA forms
cyclic compound with esterifications and several condensations, to form
mellein. Subsequently, the mellein undergo carboxylation to form ochratoxin β, and
then the ochratoxin β turned into ochratoxin α via para-chlorination reaction.
At the same time, the shikimate pathway reactions has
occurred which converted shikimic acid to phenylalanine. And finally, the
formed phenylalanine contaminated with ochratoxin α, and the ochratoxin A
finally has been produced. The final reaction involves ochratoxin A.
