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The Occurrence, Properties and Significance of Citrinin Mycotoxin

Authors:
  • Modibbo Adama University, Yola

Abstract and Figures

Citrinin is a nephrotoxic mycotoxin produced by several fungal strains belonging to the genera Penicillium, Aspergillus and Monascus. It contaminates various commodities of plant origin, cereals in particular, and is usually found together with another nephrotoxic mycotoxin, ochratoxin A. These two mycotoxins are believed to be involved in the etiology of endemic nephropathy. The mechanism of citrinin toxicity is not fully understood, especially not whether citrinin toxicity and genotoxicity are the consequence of oxidative stress or of increased permeability of mitochondrial membranes. Compared with other mycotoxins, citrinin contamination of food and feed is rather scarce. However it is reasonable to believe that humans are much more frequently exposed to citrinin than generally accepted, because it is produced by the same moulds as ochratoxin A which common contaminant of human food all over the world. Adequate knowledge of the toxin and proper food storage is essential to avoid contamination and further health and economic implication of citrinin poisoning.
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Review Article Open Access
Plant Pathology & Microbiology
ISSN: 2157-7471
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Doughari, J Plant Pathol Microbiol 2015, 6:11
http://dx.doi.org/10.4172/2157-7471.1000321
Volume 6 • Issue 11 • 1000321
J Plant Pathol Microbiol
ISSN: 2157-7471 JPPM, an open access journal
Keywords: Cereals; Citrinin; Genotoxicity; Nephrotoxicity;
Mycotoxins; Ochratoxin A
Introduction
Citrinin mycotoxin is a polyketide produced by several species of
the genera Aspergillus, Penicillium and Monascus. ough A. niger is
reported to be the highest producer of citrinin among the Aspergillus
species, other citrinin producers of this genus include A. awentil, A.
ostianus, A. fumigatus, A. niveus, A.awamori and A. parasiticus [1].
Some of the citrinin producing fungi are also able to produce the
mycotoxins ochratoxin A or patulin [2]. Citrinin is generally formed
aer harvest under storage conditions and it occurs mainly in stored
grains, but can also occur with other products of plant origin e.g. beans,
fruits, fruit and vegetable juices, herbs and spices and also in spoiled
dairy products [3].
In addition, citrinin is found as an undesirable contaminant in
Red Mould Rice (RMR), which is used as a food preservative, and
colourant in Asian foods [4]. e compound was shown to have broad
antibacterial activity, thus prompting a growing interest and research
for antibiotic agents in the middle of the last century. However,
research interest decreased when the compound was demonstrated to
have mammalian toxicity [2].
Storage of agricultural products has always been a challenge
especially in Africa. Such agricultural stored produce usually is
contaminated with a variety of fungi and pests. Consequently,
the distribution of mycotoxins in many agricultural products is
heterogeneous. It is therefore important that some of these toxins such
as the citrinins and their health implications be adequately understood
with a view to developing adequate preventive and control measures
against food contamination. is review attempts to look at the nature
and implications of citrinin in food crops [5].
Natural Occurrence
Citrinin is a mycotoxin originally isolated in 1931 by Hetherington
and Raistrick from a culture of Penicillium citrinum. e toxin is
produced worldwide in foodstus by microfungi of the genera,
Penicillium and Monascus (Table 1) and a variety of other fungi that
are found as contaminants of human foods, such as grain, cheese, sake,
and red pigments as well as in spices [3,6-8]. e fungi that produce
citrinin are major producers of other mycotoxins including ochratoxin
A and aatoxins in grains. Consequently, co-occurrence of citrinin
with ochratoxin A and aatoxin B is common in grains, particularly
rice. Simultaneous occurrence of the toxin with patulin in apple juices
and apple jams has been reported [3].
Ostry et al. [6] also reported the occurrence of citrinin in a variety
of foodstus of vegetable origin, e.g., cereals and cereal products, rice,
pomaceous fruits (e.g., apples), fruit juices, black olive, roasted nuts
(almonds, peanuts, hazelnuts, pistachio nuts), sunower seeds, spices
(e.g., turmeric, coriander, fennel, black pepper, cardamom and cumin)
and food supplements based on rice fermented with red microfungi
Monascus purpureus.. e European Food Safety Authority has also
reported contamination of cheese by citrinin where toxigenic strains
directly grow in the cheese mass [3].
Citrinin has also been found in commercial red yeast rice
supplements. In so-called the “poisoning by moldy rice” case that
occurred in Japan in 1953-54. Citrinin were found to be metabolite
of the moulds Penicillium citrinum and Penicillium expansum, both
postharvest pathogens of fruits (e.g., apple) and vegetables [7,9].
Literature data are scarce on natural occurrence of citrinin in
indoor environments. However Tuomi et al. [10] did nd citrinin in
indoor materials; they analyzed 79 bulk samples of mouldy interior
surfaces for 17 mycotoxins in buildings having moisture problems.
e collected building materials included wallpaper, cardboard, wood,
plasterboard, sand, soil, linoleum, polyurethane insulation, and paint.
ree of the 79 samples were contaminated with citrinin. But also other
mycotoxins such as sterigmatocystin, satratoxins, diacetoxyscirpenol,
deoxynivalenol, verrucarol, and T-2-tetraol were present.
*Corresponding author: Doughari JH, Department of Microbiology, School of
Pure and Applied Sciences, Modibbo Adama University of Technology, P.M.B 2076,
Yola, Nigeria, Tel: +234-7035599712; E-mail: jameshamuel@yahoo.com
Received December 01, 2015; Accepted December 10, 2015; Published
December 15, 2015
Citation: Doughari JH (2015) The Occurrence, Properties and Signicance of
Citrinin Mycotoxin. J Plant Pathol Microbiol 6: 321. doi:10.4172/2157-7471.1000321
Copyright: © 2015 Doughari JH. This is an open-access article distributed under
the terms of the Creative Commons Attribution License, which permits unrestricted
use, distribution, and reproduction in any medium, provided the original author and
source are credited.
Abstract
Citrinin is a nephrotoxic mycotoxin produced by several fungal strains belonging to the genera Penicillium,
Aspergillus and Monascus. It contaminates various commodities of plant origin, cereals in particular, and is usually
found together with another nephrotoxic mycotoxin, ochratoxin A. These two mycotoxins are believed to be involved
in the etiology of endemic nephropathy. The mechanism of citrinin toxicity is not fully understood, especially not
whether citrinin toxicity and genotoxicity are the consequence of oxidative stress or of increased permeability
of mitochondrial membranes. Compared with other mycotoxins, citrinin contamination of food and feed is rather
scarce. However it is reasonable to believe that humans are much more frequently exposed to citrinin than generally
accepted, because it is produced by the same moulds as ochratoxin A which common contaminant of human food
all over the world. Adequate knowledge of the toxin and proper food storage is essential to avoid contamination and
further health and economic implication of citrinin poisoning.
The Occurrence, Properties and Significance of Citrinin Mycotoxin
Doughari JH*
Department of Microbiology, School of Pure and Applied Sciences, Modibbo Adama University of Technology, P.M.B 2076, Yola, Nigeria
Citation: Doughari JH (2015) The Occurrence, Properties and Signicance of Citrinin Mycotoxin. J Plant Pathol Microbiol 6: 321. doi:10.4172/2157-
7471.1000321
Page 2 of 6
Volume 6 • Issue 11 • 1000321
J Plant Pathol Microbiol
ISSN: 2157-7471 JPPM, an open access journal
Physiology of Producer Cultures of Citrinin
e major genera of fungi Penicillium, Aspergillus and Monascus
spp associated with citrinin production are lamentous, and ubiquitous
in the environment. Because they live a saprophytic mode of trophic
life, they play very important role in decomposition processes of forest
liter or dung, fruits or other organic materials [11]. Filamentous fungi
when grown in culture, exhibit a high tendency towards spontaneous
morphological or physiological change [12]. Penicillium spp with more
than 150 dierent identied families are among the most commonly
occurring worldwide and economically important members of the
microfungi family. P. citrinun, the pioneer citrinin producing known
occur in natural habitats such as air, soil, rhizosphere as well as the
aqueous environment. e most important toxigenic species of
Penicilllium in foods include P. citreonigrum (which produces the
toxin citreoviridin), P. expansum (citrinin), P. citrinum (produces
citrinin), P. islandicum (cychlorotine, islanditoxin, erythroskyrin and
luteoskyrin), P. vrrucosum (ochratoxin A, citrinin) and P. crustosum
(penitrem A). In previous studies in which various toxigenic strains
of Penicillium citrinum were investigated, although, minor genetic
variations were observed, there was considerable uniformity of banding
patterns among all the strains [11,13,14]. P. citrinum is distinctively
benicillus possessing a cluster of three to ve divergent usually epically
swollen metulae carrying long-columned conidia. Colonies, 25-30 mm
on Czapek yeast extract agar (CYA) and 14–18 mm on meat extract
agar (MEA) grow optimally at 37°C aer 7 days of incubation.
Aspergillus spp, a largest aatoxin producing fungal genus grows
optimally on PDA, CYA, and MEA and produces black, small pale
brown, to yellow green depending on the species. Diagnostic features
include colour and texture of conidia, and the nature of toxin produced.
Important mycotoxic species include A. avus and A. parasiticus
(produces aatoxin A), A. ochraceus (ochratoxin A, citrinin, penicillin
acid), A. versicolor (sterigmatocystin) [15,16].
Monascus spp is also a genus comprising a wide range of fungi
producing in addition to citrinin, a very wide range of useful colour
pigment secondary metabolites including, monacolin K, yellow
monascin and ankaavin, orange monascorubrin and rubropunktatin,
red monascorubramin and rubropunktamin, monacolines, enzymes
and lipids. Monascus spp the food fungi commonly called “red rice
mold” have been consumed over the centuries in Asian countries as
Monascus-fermented rice (MFR) locally called anka, beni koji and
red yeast rice. It has been used traditionally as food colourant and
preservative, food supplement and in traditional medicine [17]. e
genus is characterized by rapid growth on red yeast rice extract agar
(RYREA), MEA with colonies beginning as white, and then maturing
into a pale pink, purple or grayish black colour depending on the
species. On RYREA, the colonies are tapetum shaped with lm shaped
little or no wrinkled or radiation patterned skin membrane. e fungi
acidophiles, with optimum pH and temperature of 3.55.0 and 32-35°C
and grows slowly on PDA [6,18]. e fungi are prototrophic, able to
utilize ammonium and nitrate nitrogen sources and glucose and under
anaerobic conditions can ferment glucose to ethanol with high yields
[16].
Biosynthesis and Genetics of Citrinin Biosynthesis
e biosynthesis of citrinin in the genus Monascus appeared to be
strain-specic and does not correlate with the pigments’ biosynthesis by
the fungal strains. e biosynthesis of the compound seem to originate
from a tetraketide instead of a pentaketide as it was found in Aspergillus
terreus and P. citrinum. ough both pigments and citrinin are derived
from the same tetraketide, their synthesis is not reciprocally mutual or
dependent upon the other. is independent level of production of each
suggests that the enzymes involved in their synthesis have independent
regulatory mechanisms of their genes. Consequently, a reduction in
citrinin synthesis does not correlate with an increase in red pigments.
Factors aecting production of these compounds and other secondary
metabolites by lamentous microorganisms include respiration rate
and hyphal morphology. Increase in respiration rate for instance makes
oxygen transfer rate and N variables relevant to the process [19].
Strain improvement for increased citrinin and pigment biosynthesis
has been reported by transformation with constructs of T-DNA
inserted into strains of Monascus ruber using the vector Agrobacterium
tumefaciens. Transformants were found to eciently integrate the
T-DNA gene into their genome and the transformed mutants were
fully stable even aer ve successive cultures. Transformed mutants
also demonstrated a greater citrinin and pigment production potential.
Present molecular studies are based on transformation models
targeting mainly functional genes for three important metabolites;
pigment, citrinin and Monacolin K. Currently, the breeding of mutant
transformant has been achieved by insertional inactivation in Monascus
chromosomal genes. In addition, site-directed knockout technology has
been developed for harmful citrinin synthase gene [17].
Factors Aecting Citrinin Production
Penicillium citrinum is one of the commonest microfungi on Earth,
occurring in all kinds of food and feed, in almost all climates. Citrinin is
produced over the range of 15–30°C and optimally at 30°C. Factors such
as a humidity of at least 16.5 ñ 19.5% favours the growth of the citrinin
producing fungi on grain [20].
Fungal growth and mycotoxin production are also aected by the
variety of agronomic practices and the nature of crops. In addition to
weather conditions during harvest, postharvest, drying and cleaning,
storage and processing conditions as well as toxigenic potential of the
mould species also aect the toxin production [21].
Decomposition of Citrinin
Because citrinin is heat sensitive, it is unstable and therefore present
in low levels in processed foods. In food processing, the compound
decomposes during heat treatment to form other complex compounds,
such as CIT H1 and CIT H2, whose cytotoxicity, compared to the
Genera Subgenus Series Species Foodstuff(examples)
Penicillium
Furcatum ------- P. citrinum Cereals, nuts, fruit
Penicillium Expansa P. expansum Fruit, cereals
Penicillium Corymbifera P. radicicola Bulbs and root vegetables
Penicillium Verrucosa P. verrucosum Cereals
Monascus M. purpureus Food supplement with fermented
red rice
M. ruber Soya bean, sorghum, rice, oat
Table 1: Penicillium and Monascus species as citrinin producers in foodstuffs (source; Ostry et al., 2013).
Citation: Doughari JH (2015) The Occurrence, Properties and Signicance of Citrinin Mycotoxin. J Plant Pathol Microbiol 6: 321. doi:10.4172/2157-
7471.1000321
Page 3 of 6
Volume 6 • Issue 11 • 1000321
J Plant Pathol Microbiol
ISSN: 2157-7471 JPPM, an open access journal
original CIT, is higher and lower, respectively. is decomposition
explains why [6].
Several studies have been carried out on degradation of citrinin
revealing that decomposition of citrinin occurs at >175°C under
dry conditions, and at >100°C in the presence of water. Known
decomposition products include citrinin H2 which did not show
signicant cytotoxicity, while the decomposition product citrinin
H1, which is made up of two citrinin molecules, showed an increase
in cytotoxicity as compared to the parent compound [20,22]. Another
decomposition product, the cytotoxic citrinin dimer, dicitrinin A, was
also reported in 2006, together with other monomeric and dimeric
degradation products [23].
Physical and Chemical Properties of Citrinin
Physical properties
Citrinin has an appearance of solid lemon-yellow needles. Its
solution changes colour in pH, from lemon-yellow at pH 4.6 to cherry-
red at pH 9.9. It has a melting point of 178.5°C. e toxin is practically
insoluble in cold water or sparingly soluble in hot water but soluble in
aqueous sodium hydroxide, sodium carbonate, or sodium acetate; in
methanol, acetonitrile, ethanol, and most other polar organic solvents
[2,20,24].
Chemical properties and chemistry of citrinin
Citrinin is a polyketide mycotoxin [C13H14O5, IUPAC: (3R,
4S)-4,6-dihydro-8-hydroxy-3,4,5-trimethyl-6-oxo-3H-2-benzopyran-
7-carboxylic acid (Figure 1); molecular weight 250.25 g/mol; CAS
No: 518-75-2]. It forms acidic lemon-yellow crystals with maximal
ultraviolet (UV) absorption in methanol, melting at 175°C with
decomposition. Citrinin crystallizes in a disordered structure, with the
p-quinone and o-quinone tautomeric forms in a dynamic equilibrium
in the solid state. It has a conjugated, planar structure which gives its
natural uorescence (the highest uorescence is produced by a non-
ionized citrinin molecule at pH 2.5 [25].
e toxin is capable of forming chelate complexes, and can be
degraded in acidic or alkaline solution, or by heating. It is a quinone,
with two intramolecular hydrogen bonds. Citrinin crystallizes in a
disordered structure, with the p-quinone and o-quinone two tautomeric
forms in a dynamic equilibrium in the solid state. In methanol or
methanol/ methylene chloride mixtures, citrinin undergoes a Michael-
type nucleophilic addition reaction. is reaction is reversible, and
the equilibrium shis toward the normal citrinin if temperature is
increased in methylene chloride [26].
In an investigation of a microbial fermentation of organic extract
of Penicillium sp, Guangmin et al. were able to isolate three derivatives
of citrinin. ese compounds are; penicitrone A (also known as
dicitrinin A), penicitrinol A, and penicitrinol B. [27]. Four new citrinin
derivatives, including two citrinin dimers and two citrinin monomer
derivatives, were isolated and identied from a marine-derived fungal
strain Penicillium sp. along with six known related compounds. eir
structures were elucidated by spectroscopic and chemical methods.
e new compounds showed modest cytotoxic activity, and weak
antimicrobial activity against Staphylococcus aureus. e isolated
compounds are: two new citrinin dimers - penicitrinone E, and
penicitrinol J; and the monomers - penicitrinol K, and citrinolactone
D; citrinolactone B, citrinin, 2, 3, 4-trimethyl-5, 7-dihydroxy-2,
3-dihydrobenzofuran, and phenol A. [28].
Laboratory Production of Citrinin
Citrinin occurs naturally, and can also be obtained as an extract.
Citrinin has mainly been found in rice, wheat, our, barley, maize, rye,
oats, peanuts and fruit and may co-occur in cereals with ochratoxin
A. However, there is limited evidence of it surviving unchanged into
cereal food products.
Chemical synthesis
e synthesis of citrinin was reported in 1949. Initially, the
laevorotatory form of 3-(4,6-dihydroxy-ortho-tolyl)butan-2-ol
is carboxylated to form the acid. is product is subjected to the
Gattermann reaction (conversion of the phenol to the aromatic
aldehyde by reaction with hydrogen cyanide/hydrogen chloride in the
presence of a zinc chloride catalyst) to produce an intermediate, which
is subsequently cyclized with sulphuric acid to form citrinin. e crude
product was puried by crystallization from ethanol. An alternative
synthetic method involves the conversion of dihydroxycitrinin to
citrinin by oxidation with bromine [29].
In another experiment, culture supernatant (10 l), was separated
from the mycelia by centrifugation (Chilspin MSE Fisons, USA) at 4°C
at 5000 rpm for 15 minutes. e supernatant was the acidied to pH 5.0
and extracted with ethyl acetate. e aqueous layer was removed and the
organic layer was concentrated and applied to a silica gel 60 preparative
TLC plate. e plates were examined under ultra violet light at 350 nm
for the presence of a pale yellow spot (Rf=0.6). e pale yellow active
compound was removed from the plate and dissolved in methanol and
again puried using HPLC (Hewlett-Packard 1090A, A Sphersorb C18,
5 µm (25 cm by 4.6 mm) column was eluted with methanol water (20:
80, v/v) at a ow rate of 1.0 ml/min. the concentration of the citrinin
was also measured in the culture supernatant spectrophotmetrically
[30].
Laboratory isolation
Citrinin was rst isolated in 1931 by Hetherington and Raistrick
from a culture of Pennicillum citrinum om. A ltrate of the culture
solution was acidied to precipitate the crude product; further
purication was achieved by recrystallization from boiling absolute
ethanol [20].
In the laboratory production process of citrinin, the Plackett-
Burman experimental design, a fractional factorial design, was used in
order to demonstrate the relative importance of medium components
on citrinin production and growth of M. ruber. Citrinin was produced
from cultures of Monascus ruber by Abdulaziz and Moustafa in a
submerged fermentation culture. Culture broth (10 ml) was centrifuged
in order to separate the fungal mycelium and the supernatant. e
supernatant was concentrated 10-fold and used for the determination
Citrinin Citrinin H1 Citrinin H2
Figure 1: Chemical Structure of Citrinin, Citrinin H1, and Citrinin H2.
Citation: Doughari JH (2015) The Occurrence, Properties and Signicance of Citrinin Mycotoxin. J Plant Pathol Microbiol 6: 321. doi:10.4172/2157-
7471.1000321
Page 4 of 6
Volume 6 • Issue 11 • 1000321
J Plant Pathol Microbiol
ISSN: 2157-7471 JPPM, an open access journal
of antibacterial activity. irty microliter (30 μl) of culture supernatant
were placed in each hole (6 mm of diameter) in Mueller-Hinton agar
medium in a Petri-dish inoculated with 0.1 ml bacterial suspension (3
× 106 cfu/ml). Petri dishes were kept for 2 h in the refrigerator and
then incubated for 12 h at 35°C and the inhibition zone diameter was
then measured. e triplicate mean values obtained were considered
the response [30].
For fungal biomass (mg/ml) determination, the sample culture aer
ltration through pre-weighed membrane lters (45-μm Millipore,
Millipore Corp., Beford, Mass., USA), washed with sterile distilled
water, and the mycelia then dried at 80°C to a constant weight [23].
Citrinin-producing fungi have been isolated on Potato Dextrose Agar
(PDA) supplemented with antibiotics such as 0.005% chloramphenicol,
grape juice agar (GJA) or yeast extract sucrose agar (YEA), [11,12].
Identication and characterization was based on estimation of
viability, morphological appearance on agar, lactophenol cotton blue
wet mount, random amplication of polymorphic DNA-polymerase
chain reaction (RAPD-PCR) and fragment length polymorphism
(AFLP) Santos, 2002; [11,13,14]. Further estimation and purication
of citrinin levels have been achieved by various methods including
thin layer chromatography (TLC) [11,12]. Other analytic methods
for citrinin include colorimetric, uorimetric, chromatographic
techniques such as high performance liquid chromatography with
uorescence detection (HPLC-FLD), liquid chromatography mass
spectrometry (LC-MS), gas chromatography mass spectrometry (GC-
MS) and immunochemical methods suchas EL:ISA (enzyme linked
immunosorbent assay) [1,3,31].
Pharmacological and Chemotherapeutic Potentials of
Citrinin
Citrinin is believed to be involved in the aetiology of endemic
nephropathy. In addition to nephrotoxicity, Citrinin is also
embryocidal and fetotoxic. e genotoxic properties of Citrinin have
been demonstrated with the micronuleus test (MN), but not with
single-cell gel electrophoresis. e mechanism of citrinin toxicity
is not fully understood, especially not whether citrinin toxicity and
genotoxicity are the consequence of oxidative stress or of increased
permeability of mitochondrial membranes. citrinin requires complex
cellular biotransformation to exert mutagenicity [32].
Antibacterial/antifungal potentials
Citrinin has weak activity against Gram-positive bacteria, including
Staphylococcus aureus, Bacillus subtilis, and Micrococcus luteus. It was
almost or very ineective against Gram-negative bacteria, yeasts, and
molds. Interestingly, however, citrinin tended to inhibit the growth of
some yeasts and molds in malt wort adjusted to acidic pH.
e mycotoxin citrinin had antifungal activity under acidic
conditions. At the minimum inhibitory concentration, it completely
inhibited cellular respiration and partially inhibited the incorporation
of radioactive precursors into macromolecules in Saccharomyces
cerevisiae. It had no eect on cell permeability. In mitochondrial
preparations, it signicantly inhibited succinate oxidase and NADH
oxidase. Rhizopus chinensis was more sensitive than S. cerevisiae; its
growth and mycelial respiration at acidic pH were completely inhibited
by lower concentrations of citrinin. e pH-dependent antifungal
activity of citrinin seems to be associated with its uptake by fungi.
Approximately half of the citrinin taken up was found in mitochondria.
e main site of the antifungal action of citrinin, therefore, appears to
be the mitochondrial electron transport system [32].
Anticancer potentials
A variety of citrinin derivatives from dierent fungal species
demonstrated antitumor potentials showing that Citrinin might be a
precursor of novel active compounds against cancer disease [9].
Red yeast rice has been used in chinese medicine to strengthen
the spleen, promote or improve digestion, eliminate dampness and
phlegm, promote or improve blood circulation, and remove blood
stasis. During the Ming Dynasty, red yeast rice was described as “sweet
in avor and warm in property.” e genus Monascus has been used
for centuries in Asia as a source of pigment for coloring traditional
foods. e medicinal properties of red yeast rice are valued throughout
Asia [33].
Other Biotechnological Applications of Citrinin
Red yeast rice (which contains citrinin) has been used to make rice
wine and as a food preservative for maintaining the color and taste of
sh and meat. Commercial food applications include coloration of
sausage, hams, surimi, and tomato ketchup. e pigment has a long
history of use as a food ingredient for Asian consumers, but not in
Europe or America. However, a recent study documents the registration
of numerous patents obtaining the use of Monascus as a food pigment
in Japan, the United States, France, and Germany. Because citrinin
is produced in by contaminating fungi, it has the potential of being
developed into bio-weapon to be fed to hungry population of a war-
torn country [9,20].
Health Implications of Citrinin Exposure
Citrinin represents a severe problem especially in countries with
a hot climate as under these conditions it is a major source of food
poisoning aer fungal contamination [34]. Citrinin (CIT), oen
found in the same food as ochratoxin A, is a powerful nephrotoxin
[6]. In repeat dose toxicity studies, the kidney was identied as the
principal target organ for CIT, and signicant species dierences in the
susceptibility to CIT have been observed. e renal system of humans
was found to be aected, and the mitochondrial respiratory chain was
identied as a possible sensitive target for CIT. A few studies have also
addressed its potential for immunotoxicity [35,36]. In animals and
humans the toxin accumulates in the kidneys and can cause severe
renal failure. Physiological investigations identied dierent adverse
eects on the kidneys, liver and the gastrointestinal tract [33].
It has been suggested that citrinin may be implicated in the fatal
human kidney disease, Balkan Endemic Nephropathy, along with other
mycotoxins including ochratoxin A and further unidentied toxins.
Citrinin can act synergistically with the ochratoxin A to attenuate the
activity of RNA synthesis in kidney tissue.
Recently additive and synergistic nephrotoxic eects of citrinin in
combination with other mycotoxins such as ochratoxin A have been
described. e mycotoxin complex so formed, disrupted RNA synthesis
in kidney tissue thereby further complicating its nephrotoxic potentials.
Citrinin-Ochrotoxin A complex formation has been associated with
alterations in renal function and/or with the development of renal
pathologies. Simultaneous co-exposure to citrinin and ochratoxin A
has also been reported to result in the modication of DNA adduct
formation with increasing formation of the C-C8dG-OTA adduct
[6]. e mycotoxin and ochratoxin complex A also are reported to be
causative agents of hepatorenal carcinogenesis [8,26].
Citrinin can be poisonous by ingestion and other routes, an
experimental teratogen, other experimental reproductive eects
Citation: Doughari JH (2015) The Occurrence, Properties and Signicance of Citrinin Mycotoxin. J Plant Pathol Microbiol 6: 321. doi:10.4172/2157-
7471.1000321
Page 5 of 6
Volume 6 • Issue 11 • 1000321
J Plant Pathol Microbiol
ISSN: 2157-7471 JPPM, an open access journal
a severe skin irritant, questionable carcinogen with experimental
neoplastigenic and tumorigenic data and mutation data reported.
When heated to decomposition it emits acrid smoke and irritating
fumes.
Citrinin has been associated with yellow rice disease in Japan. It has
also been implicated as a contributor to porcine nephropathy. Citrinin
acts as a nephrotoxin in all animal species tested, but its acute toxicity
varies in dierent species. e lethal dose for ducks is 57 mg/kg; for
chickens it is 95 mg/kg; and for rabbits it is 134 mg/kg . Citrinin can act
synergistically with ochratoxin A to depress RNA synthesis in murine
kidneys [37].
Exposure to mycotoxins through inhalation and skin contact can
occur in indoor environments. However, the extent of possible health
hazards caused by inhaled mycotoxins or through dermal exposure of
mycotoxins is largely unclear [38].
Control of Citrinin Contamination
In order to control and prevent citrinin contamination, food
containers should be tightly closed and kept in a well-ventilated
place. Suitable protective clothing such as gloves, eye/face protection
materials etc., should be worn at all times when coming in contact with
items susceptible to citrinin contamination. In case of ingestion or
contact with contaminated substances, it is appropriate to seek medical
attention immediately.
Conclusion
e mycotoxin citrinin has both potentially important
pharmacological applications as well as some signicant medical
implications. erefore, extraction and purication of the metabolite
and further toxicological studies will enable its appropriate
understanding with a view to exploiting its usefulness, and controlling
its harmful eects. Citrinin has been shown to produce serious illnesses
in animals and even death. And its health implications to humans
include irritation when contact is made in the eyes or skin.
ere is a need for more data regarding the occurrence of citrinin
in food and feed. ere is a need for certied reference materials and
dened performance criteria for the analysis of citrinin in food and feed.
ere is a need for well-designed toxicological studies in laboratory
animal species to further explore the toxicological potential of citrinin
and to characterize the dose-response relationships. ere is a need for
more data on farm animal toxicity and the carryover of citrinin from
the feed to animal products intended for human consumption. ere is
also the need to public enlightenment and sensitization on the sources,
eects and prevention of citrinin contamination.
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7471.1000321
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... Mycotoxins are low molecular weight secondary metabolites produced by various fungal genera, including Aspergillus, Fusarium, and Penicillium (Doughari 2015). These toxins develop when fungi grow on different substrates under suitable conditions (Richard 2007;Tola and Kebede 2016). ...
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... The fluorescence of these spots was compared to standard mycotoxins, and the Rf value of the spot was determined to be 0.63. Based on this comparison, the mycotoxins produced by Aspergillus niger in this study were identified as Citrinin (Rasheva et al. 2003;Doughari 2015). Since the spots were faint and fragile, the TLC plate was sprayed with aluminum chloride, which caused the spots to change from yellow to blue. ...
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... while without tarpaulin are 76 (53.1%). The results also corresponds to other studies that showed majority used polypropylene woven sacks while few used jute sacks [20][21][22][23][24][25][26][27][28][29]. Another study showed 57% store their finished products in polyethylene bags and 20% in leaves for an average of seven days. ...
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Chapter
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The mycotoxin citrinin had antifungal activity under acidic conditions. At the minimum inhibitory concentration, it completely inhibited cellular respiration and partially inhibited the incorporation of radioactive precursors into macromolecules in Saccharomyces cerevisiae. It had no effect on cell permeability. In mitochondrial preparations, it significantly inhibited succinate oxidase and NADH oxidase. Rhizopus chinensis was more sensitive than S. cerevisiae', its growth and mycelial respiration at acidic pH were completely inhibited by lower concentrations of citrinin. The pH-dependent antifungal activity of citrinin seems to be associated with its uptake by fungi. Approximately half of the citrinin taken up was found in mitochondria. The main site of the antifungal action of citrinin, therefore, appears to be the mitochondrial electron transport system.
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Maize flour treated with or without Tribolium castaneum was investigated for the presence of some fungi. Fusarium moniliforme had the highest occurrence of 36.7%, 28.1% and 33.3% while Aspergillus flavus/parasiticus had a frequency of 3.2%, 3.1% and 3% on primary isolation media of czapek dox agar (CDA), potato dextrose agar (PDA) and sabouraud dextrose agar (SDA) respectively, in maize flour without T. castaneum. The frequency of F. moniliforme reduced in maize flour with T. castaneum to 11.1%, 12.1% and 18.8% on CDA, PDA and SDA while A. flavus/parasiticus increased in occurrence after introducing T. castaneum to 22.2%, 18.2% and 12.3% on the three respective media. Fourteen and 7 fungal genera were isolated from maize flour with and without F. castaneum respectively. Two fungal species isolated from maize flour without T. castaneum were Cladosporium cladosporioides and C. lunata. Ten species isolated from maize flour with T. castaneum were A. pullulans, Auxarthron spp., C. herbarum, Eurotium sp., Phoma glomerata, Neosauorya spp., Scopulariopsis brevicaulis, Rhizopus oryzae, R. stolonifer and Wallemia sebi. These results suggest an association and a synergistic interaction between important spoilage and mycotoxigenic fungi with T. castaneum such as A. flavus/parasiticus and some mildly parasitic fungal colonies but an antagonistic interaction with F. moniliforme. Key words: Tribolium castaneum, storage fungi, synergistic/antagonistic interactions, mycotoxins (Af. J. Food and Nutritional Sciences: 2001 1(1): 3-8)