Mycotoxins and their impact on human and animal health

MYCOTOXINS AND THEIR IMPACT ON HUMAN AND ANIMAL HEALTH

Al-Zahraa Mamdouh1 and Eman Zahran2* Fish Diseases Department, National Institute of Oceanography and Fisheries (NIOF), Egypt 1

Department of Internal Medicine, Infectious and Fish Diseases, Faculty of Veterinary Medicine, Mansoura University, Mansoura, Egypt 2

*Corresponding author: emanzahran@mans.edu.eg

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Mycotoxins are toxic substances produced naturally by filamentous fungi as secondary metabolites that can be found in food for humans and feed for livestock.

Cereals, nuts, corn, and rice can be contaminated in the field during harvest or storage, making them a common source of contamination.

Most mycotoxins have been shown to be toxic, nephrotoxic, hepatotoxic, carcinogenic, immunosuppressive, and mutagenic in animal studies, and they pose a serious threat to human and animal health.

Mycotoxins that have been chemically characterized and are currently the subject of research because of their demonstrated potential toxicity are described in this review.

The threat of mycotoxins Mycotoxins are produced naturally as

These toxins are produced by fungal

secondary metabolites with no known

species belonging mainly to:

metabolic function by filamentous fungi

(Edite Bezerra da Rocha et al., 2014).

They are considered toxic substances

Aspergillus Fusarium

when present in human

Alternaria

food or animal feed.

Penicillium

They can appear during pre-harvest, post-harvest, processing, storage, and feeding.

Besides, they are commonly found in human and animal food derivatives (Sforza et al., 2006).

Myrothecium Trichothecium Verticimonosporium (Zain, 2011)

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Mycotoxins are one of the main classes

Direct contamination occurs through

of naturally occurring toxic substances

the infection of the food by a toxigenic

contaminating food and feed worldwide

fungus with subsequent production

(Hueza et al., 2014; Shetty et al., 2006; Taheur et al., 2017).

of mycotoxins, whereas indirect contamination occurs through previous contamination of food ingredients by a toxigenic fungus, even though it has been eliminated during processing (Edite

25%

According to the Food and

Bezerra da Rocha et al., 2014).

Agriculture Organization (FAO), about 25% of the food produced

Factors enhancing mold growth and

in the world is contaminated

mycotoxin production include weather

with at least one mycotoxin

conditions, particularly humidity levels

(Rogowska et al., 2019).

(above 70%) and temperature (20–30°C).

Additionally, the plant’s moisture content (above

Contamination of animal and human food

15%), mechanical damage, damage to crops by

with mycotoxins occurs directly or indirectly.

insects, substrate composition, use of pesticides, plant variety, and spore load influence the production of mycotoxins (Streit et al., 2012).

Humidity (>70%)

Temperature (20-30°C) Mechanical damage

Plant moisture

PREDISPOSING FACTORS FOR MOULD GROWTH AND MYCOTOXIN PRODUCTION

Plant variety

Damage from insects Mycotoxin-containing ingredients used in preparing food and feedstuffs have less

Substrate composition Use of pesticides

nutritional value and represent a risk for animal and human health (Matejova et al., 2017).

Spore load

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Major mycotoxins that pose a risk to human and animal health Aflatoxins Aflatoxins are difuranocoumarin derivatives that are produced in a variety of food, including maize, groundnuts, rice, sorghum (Kew, 2013), pistachio, groundnuts, tree nuts (almonds,

Additionally, aflatoxin M1, a hydroxylated form of aflatoxin B1, is formed in animal tissues and fluids as a metabolite of AFB1

(Neal et al., 1998), whereas aflatoxin M2 is a

walnut, hazelnut, brazil nuts), cottonseed,

metabolite of aflatoxin B2 formed in cattle

spices, dried fruits, cereals, soybean, cocoa,

milk (Dhanasekaran et al., 2011).

milk, milk products, and meat (Patriarca y Pinto, 2017; Vila-Donat et al., 2018).

Several factors enhance the production of aflatoxins.

They are produced mainly by Aspergillus

flavus and A parasiticus and, to a

For example, tropical and sub-tropical

lesser extent, A nomius, A bombycis,

regions characterized by high temperatures

Aspergillus pseudotamari and Aspergillus ochraceoroseus (Varga et al., 2011).

and humidity, along with moisture content of the plants, have favorable conditions for the growth of Aspergillus and the

Based on their blue or green fluorescence

production of aflatoxins (Kew, 2013).

under ultraviolet light, the main known aflatoxins are B1, B2, G1 and G2.

The most favorable temperature for their production is 25-32˚C, as well as moisture contents over 12% and less than

AFB1 and AFB2 are produced mainly by A.

16%, and relative humidity of 85%.

flavus, while others are produced by A. parasiticus (Dhanasekaran et al., 2011).

Other types of aflatoxins include P1, Q1, B2A and G2A, which are formed due to biotransformation or metabolism of aflatoxins in humans and animals (Doi et al., 2002).

IDEAL CONDITIONS FOR PRODUCTION OF AFLATOXINS Temperature: 25-32˚C Moisture: 12-16% Relative humidity: 85%

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MECHANISMS OF TOXICITY AND EFFECTS Aflatoxins are the most researched group of mycotoxins due to their carcinogenic and toxic effects in laboratory animals and livestock (Jha et al., 2013; Rotimi et al.,

2017), as well as their acute and chronic hepatocarcinogenic and toxicological effects in human beings (Asim et al., 2011; Kew, 2013).

These ROS target cellular DNA, RNA, Aflatoxin toxicity arises mainly from

proteins, and cell membranes, leading

the generation of intracellular reactive

to the impairment of cell function,

oxygen species (ROS), such as superoxide

oxidative stress, DNA damage, cytolysis,

anion, hydroxyl radical, and hydrogen

and apoptosis (Asim et al., 2011; Yang

peroxide (H2O2), during its metabolism

et al., 2016). In addition, they can target the p53 tumor suppressor gene causing hepatocarcinoma (Kew, 2013).

by cytochrome P450 in the liver.

AFLATOXIN ROS Hepatocarcinoma

P53 TUMOR SUPPRESSOR GENE

DNA RNA Proteins Cell membranes

Impaired cell function Oxidative stress DNA damage Cytolysis Apoptosis

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Hepatotoxicity

The metabolism of aflatoxins occurs mainly in the liver under the action of cytochrome P450s into electrophilic, reactive epoxide which, in turn, binds to DNA, RNA, and cellular macromolecules in the liver (Abrar et al.,

2013).

Aflatoxins are usually associated with the development of hepatocellular carcinoma (HCC) in humans due to their mutagenic and carcinogenic properties.

Levels of serum liver enzymes were changed upon administration of AFB1 through intraperitoneal injection

In fact, they are considered a significant risk factor, alongside the hepatitis B virus (HBV) and the hepatitis C virus (HCV), for HCC (Bosetti et al., 2014).

in 5-week-old male Wistar rats.

It also increased malondialdehyde (MDA) and decreased glutathione, catalase (CAT), superoxide dismutase (SOD), and glutathione peroxidase (GPx) levels (Ji et al., 2020).

Similar oxidative stress was represented by increased MDA levels and decreasing

AFB1 is the most potent experimental

glutathione content (GSH) and altered liver

hepatocarcinogen known (Humans and

enzyme levels in rats exposed to AFB1

Cancer, 2002) and no animal model exposed to the toxin has failed to develop HCC.

Nile tilapia (Oreochromis niloticus)

(Karaca et al., 2021; Vipin et al., 2017).

exposed to AFB1 suffered from oxidative It also accounts for approximately

stress and hepatic damage indicated by

9.2 % of all new cancers worldwide

liver damage biomarkers represented

(Ferlay et al., 2010). Other liver diseases, including cirrhosis (Humans, 2014) and hepatomegaly (Gong et al., 2012), have also been reported as implications of aflatoxin-induced toxicity in humans.

by decreased CAT activity, GPx,

Liver function and oxidative stress are expected consequences

and SOD levels and increased MDA content (Ben Taheur et al., 2022).

Matrinxã (Brycon cephalus) and Pacu

(Piaractus mesopotamicus) showed fatty degeneration, liver damage and altered levels of liver enzymes following dietary exposure to AFB1 (Michelin et al., 2021).

of af aflatoxicosis in fish and experimental animals.

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Immunosuppressive effects

Effects on reproduction

The immunosuppressive effects of aflatoxins

The hepatotoxic and carcinogenic effects of

have been thoroughly investigated in

aflatoxins in mammals and aquatic organisms

human, poultry, and aquatic species.

have been intensively reviewed, unlike their effects on reproduction. The mechanism

AFB1 is toxic to human lymphocytes and

of reproductive toxicity of aflatoxin is not

its cytotoxicity is mediated by apoptosis

fully understood (Shuaib et al., 2010), but

and necrosis (Al-Hammadi et al., 2014),

previous studies reported that exposure to

and it has been shown to suppress the

aflatoxins induces toxic effects on testis and

alternative pathway of complement activation

other reproductive organs with subsequent

(APCA) in ducks (Valtchev et al., 2015).

impairment of spermatogenesis.

Lymphocyte percentage, avian influenza

It was found that abnormalities in semen

antibody titer relative to thymus weight, and

parameters (volume, viscosity, pH, fructose,

immune response to phytohemagglutinin

spermatozoa count, morphology, and

were decreased in broiler chickens

motility) were evident in infertile men

exposed to AFB1 (Rashidi et al., 2020).

showing highly significant blood and semen aflatoxin levels when compared to their

Similarly, dietary exposure of broiler

level in fertile men (Uriah et al., 2001).

chickens to AFB1 induced immune suppressive effects, including a reduction

Varieties of significant changes

in the immune response to sheep red

in reproduction indexes were

blood cells (SRBCs), phagocytic clearance

detected in male Wistar rats injected

of carbon particles, and PHA-P-mediated

intramuscularly with 20 µg AFB1/kg

cutaneous basophilic hypersensitivity, along

body weight (Supriya et al., 2014).

with degeneration, necrosis, and depletion of lymphoid tissue (Bhatti et al., 2021).

Furthermore, AFB1 was proved to cause

AFB1 reduced bactericidal activity,

as degeneration and necrosis of epithelial

lysozyme activity, and total serum protein

cells of sperm tubules with decreased

level in yellow catfish (Pelteobagrus

sperm number (Murad et al., 2015).

pathological changes in the epididymis, such

fulvidraco) (Wang et al., 2016).

Similarly, lysozyme activities, total immunoglobulin contents, and complement C3 and C4 activities were significantly decreased in the plasma of common carp fed with a diet containing aflatoxins (Bitsayah et al., 2018).

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Fumonisins Fumonisins are produced mainly by Fusarium verticillioides (also known as Fusarium moniliforme), Fusarium proliferatum, Fusarium nygamai, and other Fusarium species, such as Fusarium anthophilum, Fusarium dlamini, Fusarium napiforme, Fusarium subglutinans, Fusarium polyphialidicum and Fusarium oxysporum (Scott, 2012).

There are 16 known types of Fumonisins, referred to as B1 B1 (FB1, FB2, FB3 and FB4), A1, A2, A3, AK1, C1, C3, C4, P1, P2, P3, PH1a and PH1.

They are usually found in corn and corn-based foods (Marasas, 2001).

FB1 is the most commonly found in a list of food and feedstuff other than corn, such as rice, sorghum, beer, triticale, cowpea seeds, beans, soybeans, and asparagus (Scott, 2012).

MECHANISMS OF TOXICITY AND EFFECTS FB1 has a neurotoxic effect in equines as

It is carcinogenic, hepatotoxic, nephrotoxic (Szabó

it causes leucoencephalomalacia in horses

et al., 2019; Szabó et al., 2018), and embryotoxic (Lumsangkul et al., 2019) in laboratory animals, while in humans, fumonisins are associated with oesophageal cancer (Yu et al., 2021) and neural tube defects (Copp et al., 2013).

(Vendruscolo et al., 2016), while its target organ in swine is the lungs as it causes porcine pulmonary edema in pigs (Freitas et al., 2012).

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Fumonisins exert their toxic effects mainly

It has been further suggested that the

by inhibiting the ceramide synthase

pathogenesis of pulmonary edema in swine and

enzyme, which is essential for the

cardiotoxicity in horses exposed to FB1 is partly

synthesis of ceramide from sphinganine

due to inhibition of L-type calcium channels in

and sphingosine (Voss y Riley, 2013).

the heart caused by the accumulated sphingosine and sphinganine, which then leads to left-sided cardiac insufficiency (Voss et al., 2007).

Ceramides are the basic structural components of all sphingolipids (found in the cellular membranes of animals

In addition, the carcinogenic effect of

and plants) (Engelking, 2015).

fumonisins in humans is related to impaired sphingolipid biosynthesis, which leads to

As a result, both sphinganine and

impairment of cellular activity as they are part

sphingosine accumulate following

of cellular membrane composition and essential

enzyme inhibition causing apoptosis

for cell-cell communication, intracellular and

of renal tubule cells and hepatocytes

cell-matrix interactions, and growth factors

(Voss and Riley, 2013).

(Edite Bezerra da Rocha et al., 2014).

FUMONISIN

CERAMIDE SYNTHASE ENZYME INHIBITION

Accumulation of sphinganine and sphingosine

Apoptosis in renal tubule cells and hepatocytes Inhibition of L-type calcium channels in the heart (cardiotoxicity)

Impaired sphingolipid synthesis

Carcinogenicity due to impaired cellular activity

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H O

O OH

HO

Trichothecenes

O HO

Trichothecenes are toxic secondary metabolites produced in host plants, food, and other organic matrices by several fungal genera, including

Fusarium, Microcyclospora, Myrothecium, Peltaster, Spicellum, Stachybotrys, Trichoderma, and Trichothecium. Among them, Fusarium trichothecenes are of most significant concern to food and feed safety (Proctor et al., 2018).

There are more than 150 toxins belonging to the trichothecenes family, but the most important ones are deoxynivalenol (DON), nivalenol (NIV), toxin T2, toxin HT2 and diacetoxyscirpenol (DAS) (Yang et al., 2015).

Like most mycotoxins, they are a significant food safety concern because of the harmful effects they induce from acute and chronic exposure to them (Sobrova et al., 2010). DON is the most commonly found trichothecene in cereal grains (Tian et al., 2016).

MECHANISMS OF TOXICITY AND EFFECTS Trichothecenes are known for their capacity to

These toxins can also inhibit DNA and RNA synthesis (Minervini et al., 2004), alter cellular membrane structure (Diesing

et al., 2011), mitochondrial function, and arrest the cell cycle (Pestka, 2010a).

inhibit eukaryotic protein synthesis by binding to the 60S subunit of the eukaryotic ribosomes

They can also induce oxidative stress via

and inhibiting peptidyl transferase activity,

increasing lipid peroxidation and alteration of

which eventually leads to inhibition of the

antioxidant defenses, which eventually impair

initiation, elongation, or termination of the

protein synthesis and cause DNA damage

chain elongation step in protein synthesis

(Doi and Uetsuka, 2011; Wu et al., 2014).

(Arunachalam and Doohan, 2013).

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TRICHOTHECENES H O

O OH

HO

O

Protein synthesis inhibition

HO

DNA/RNA SYNTHESIS INHIBITION

PEPTIDYL TRANSFERASE INHIBITION (60S)

ALTERED MITOCHONDRIAL FUNCTION OXIDATIVE STRESS ALTERED MEMBRANE STRUCTURE

Impaired protein synthesis DNA damage

CELL CYCLE ARREST

T-2 toxin significantly increased ROS

glutathione reductase (GR) and glutathione

levels, decreased GSH, and elevated lipid

peroxidase (GPx) and decreased in catalase

peroxidation leading to single-strand

(CAT) activity (Modra et al., 2018).

breaks in DNA In human cervical cancer cells (Chaudhari et al., 2009).

In the same fish species, significant alterations in activities of GPx in the

Elevated concentrations of DON increased

kidney, GR in the gill and kidney, CAT

ROS levels leading to cell death in a

in the kidney and liver, and GST in the

human cell line (Costa et al., 2009).

gill and liver followed dietary exposure to DON (Šišperová et al., 2015).

Dietary exposure of rainbow trout

(Oncorhynchus mykiss) to 0.01 mg/ kg b.w. and 0.018 mg/kg b.w T-2 toxin increased lipid peroxidation and the activities of glutathione-S-transferase (GST),

Trichothecenes are well known for inducing apoptosis and programmed cell death (PCD) via ROS- mitochondrialmediated pathway (Zhuang et al., 2013).

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T-2 toxin treatment of ovarian granulose cells of rats caused typical apoptotic morphological changes, such as nuclear fragmentation and reduction in mitochondrial membrane potential, due to the up-regulation of pro-apoptotic proteins p53 and Bax, higher Bax/ Bcl-2 ratio, and the activation of caspase 3 pathway (Wu et al., 2011).

In addition to biological biomarkers for detection It also induced increased ROS production

of trichothecene toxicity, clinical symptoms are

and cell apoptosis, mainly in the tail areas

often associated with digestive tract disorders

of zebrafish embryos revealed by Acridine

where DON contamination in cereal grains

Orange staining (Yuan et al., 2014).

causes severe gastrointestinal disorders

In human chondrocytes, T-2 toxin-induced apoptosis was associated with increased Fas, p53, pro-apoptotic factor Bax, and caspase 3, and downregulation of anti-apoptotic factor Bcl-xl expression (Chen et al., 2008).

including nausea, vomition, diarrhea, and abdominal pain in humans (Pestka, 2010b; Pinton et al., 2012) and in animals.

It can cause weight loss and the refusal to eat when ingested by swine and other animals in small doses (vomitoxin or food refusal factor) (da Rocha et al., 2014).

Zearalenone Zearalenone (ZEN), also referred to as the

This toxin is a xenoestrogen, which means

F-2 or RAL mycotoxin, is a non-steroidal

that it is a type of xenohormone that

estrogenic secondary metabolite biosynthesized

imitates estrogens (sex-steroid hormone

mainly by Fusarium graminearum and to

mimicry) (Zahran et al., 2021).

a lesser extent by Fusarium culmorum,

Fusarium cerealis, or Fusarium equiseti (De Boevre et al., 2012; Taheur et al., 2017).

It has genotoxic (Braicu et al., 2016; Taranu

et al., 2015), immunotoxic (Assumaidaee et al., 2020; Hueza et al., 2014), teratogenic, carcinogenic (Abassi et al., 2016), hematotoxic and hepatotoxic properties (Bai et al., 2018) but its toxicity to human and animal arises mainly from its xenosteroidal activities.

Its chemical structure is similar to naturally occurring estrogen and it exerts its action by acting as an endocrine-disrupting compound (EDCs) (Rogowska et al., 2019), potentially changing the functions of the endocrine system in living creatures and causing adverse health effects. In fact, they are known to prompt alterations in hormonally monitored physiological functions (homeostasis, growth, development, and reproduction) (Kar et al.,2021).

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MECHANISMS OF TOXICITY AND EFFECTS Zearalenone exerts its action by imitating

Either way, reproductive impairment is the

naturally occurring estrogens (leading to

final outcome (Rogowska et al., 2019).

a similar outcome as natural estrogens) or competing with their receptors (leading to an antiestrogenic reaction).

ZEARALENONE Estrogenic effects Reproductive impairment IMITATION OF NATURAL ESTROGEN

Antiestrogenic effects COMPETITION FOR ESTROGEN RECEPTORS

Dietary exposure of piglets to 1mg/kg

Similarly, low doses of ZEN affected

ZEN induced reproductive impairment

mice’s male reproductive capacity with a

represented by an increase in the length,

significant decrease in spermatogenic cells,

width, and area of the vulva, the genital

sperm concentration, viability, motility,

organ coefficient, and a significant decrease

and hyperactive rate and a significant

in E2, LH, and FSH (Su et al., 2018).

increase in the DNA double-strand break in spermatogenic cells, in addition to a significant increase in deformity and mortality rate of sperm (Pang et al., 2017).

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In fish, several studies reported the effect of zearalenone on reproductive performance, including impaired reproduction of rainbow trout and induced high sperm concentration and high plasma vitellogenin levels in males, and induced early ovarian development in females (Woźny et al., 2020).

In the same line, zearalenone induced vtg-1 mRNA expression in zebrafish

The mechanism of zearalenone-associated immunotoxicity

(Danio rerio) in a concentrationdependent manner following 120 h exposure (Bakos et al., 2013).

arises because it is a xenoestrogen and EDC. Estrogens not only function as reproductive hormones. They also have non-reproductive functions, also affecting immune functions. In this respect, estrogens act on immune cells via estrogen receptors (ERs) which enable them to act either in an immunomodulatory (Islam

et al., 2017) or immunosuppressive way (Abbès et al., 2013; Zahran et al., 2021).

Ochratoxins Ochratoxins are dihydroisocoumarin bonded to phenylalanine pentaketide metabolites. They are classified as ochratoxin A (OTA), produced by Aspergillus ochraceus, and ochratoxin A, B, and C, produced by other Aspergillus and Penicillium species (Marroquín-Cardona et al., 2014).

Ochratoxins have been found to contaminate various foods like grains, rice, wheat, dried fruit, coffee, cocoa, wine, beer, and foods of animal origin, particularly pork (Kumar et al., 2020).

OTA is the most predominant ochratoxin found in food and feed across the world, and it is the most toxic form comprising significant risk to human and animal health.

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MECHANISMS OF TOXICITY AND EFFECTS OTA induces toxicity by binding to

It induced hepatotoxicity in rats marked

proteins, particularly serum albumins,

by a significant decrease in SOD, CAT, and

with subsequent bioaccumulation in its

GPx activities, a significant increase in MDA

target organs (Duarte et al., 2012).

level, and histopathological lesions in the liver, including inflammation, steatosis,

It is also an inhibitor of the nuclear factor

necrosis, and fibrosis (Damiano et al., 2021).

erythroid 2–related factor 2 (Nrf2), thus inducing physiological oxidative stress,

In another study, OTA exposure was

further damaging the DNA (Limonciel

associated with a significant increase in

and Jennings, 2014).

pro-inflammatory and DNA oxidativedamage biomarkers and a significant

OTA is mainly nephrotoxic:

increase in nitric oxide (NO) levels in kidneys and liver (Longobardi et al., 2021).

In humans, it is responsible for human

The carcinogenic effect of OTA was reported

Balkan endemic nephropathy (BEN)

in rats represented by increased mRNA

(Stiborová et al., 2016), chronic interstitial nephropathy (CIN) (Hassen et al., 2004), renal failure, and tumors (Chen and Wu, 2017; Hope and Hope, 2012).

levels of clusterin in kidneys, increased proliferation of cell nuclear antigen (PCNA) in liver and kidney, down-regulation of reactive oxygen species (ROS) and p53 gene, and up-regulation of vimentin and

In pigs, it causes endemic

lipocalin in the kidney (Qi et al., 2014).

porcine nephropathy (Jørgensen

and Petersen, 2002).

Furthermore, Liver and kidney impairment was evident in Nile tilapia exposed to

It is also carcinogenic, classified as a

OTA (Mansour et al., 2015), while it

Group 2B possible human carcinogen

induced hepatic failure and antioxidative

(Marroquín-Cardona et al., 2014).

suppression in Thinlip Mullet (Liza

ramada) (Magouz et al., 2022).

Ruminants and rodents are, to some extent, resistant to OTA because their microbiota can produce carboxypeptidase enzymes.

The enzyme can cleave the peptide bond and form less toxic OTα

(Abrunhosa et al., 2006).

Despite that fact, OTA is hepatotoxic, teratogenic, immunotoxic, and carcinogenic in experimental models.

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Decontamination of mycotoxins in experimental models Mycotoxins in feed necessitated the

Dietary supplementation of rutin in

development of novel technologies that

Nile tilapia improves growth, elevated

would be useful, environmentally friendly,

liver antioxidant capacity, and reduced

and cost-effective in their removal.

liver and myofiber damage induced

by T-2-toxin (Deng et al., 2019).

Examples of some compounds used to ameliorate mycotoxin toxicity are described as follows.

Oxidative damage and hepatopancreas immune responses induced by T-2 toxin in Chinese mitten crab (Eriocheir sinensis) are reduced following dietary supplementation with arginine (Zhang et al., 2020).

Sodium selenite exhibits protective effects on AFB1-induced toxicity by inhibiting

Vitamina C supplementation

oxidative stress and excessive apoptosis

diminishes reproductive, immune,

in broilers’ spleen (Wang et al., 2013),

and hematological toxicity in piglets

decreasing DNA damage and histological

exposed to ZEN (Su et al., 2018).

alterations in ducklings’ liver (Shi et al.,

2015), and ameliorating reproductive toxicity in mice (Cao et al., 2017).

Resveratrol (RSV) is able to decrease or reverse ZEN-induced toxicity in adult male Wistar rats, enhancing antioxidant enzyme

Silymarin administration alleviates elevated Vascular endothelial growth factor (VEGF) and fibroblast growth factor-2 (FGF-2) expression levels and diminishes liver damage induced by FB1 in mice (Sozmen et al., 2014) .

activity and improving immune parameters

Lactobacillus paracasei alleviates genotoxicity, oxidative stress status, and histopathological damage induced

by FB1 in mice (Ezdini et al., 2020),

(Longobardi et al., 2021).

while Lb. delbrueckii subsp. lactis (LL) and P. acidilactici (PA) strains induced a

in exposed rats (Virk et al., 2020).

Curcumin modulates nitrosative stress, inflammation and DNA damage, hepatotoxicity, and nephrotoxicity induced by Ochratoxin A in Rats

Green tea-mediated zinc nanoparticles ameliorate the hepatotoxicity and nephrotoxicity induced by OTA in albino rats (Mansour et al., 2015).

protective effect against antigenotoxicity and precancerous lesions caused by FB1 in Sprague-Dawley Rats (Khalil et al., 2015) .

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Selenium-enriched probiotics (SP) enhance

The protective role of Minazel® Plus on fish

kidney functions, growth performance,

health is evidenced in growth performance,

and antioxidant parameters in piglets

hematological parameters, innate immune

intoxicated with OTA (Gan et al., 2021).

and antioxidant responses, bioaccumulation

Whey supplementation ameliorates ochratoxicosis in Nile tilapia (Mansour et

al., 2015) and dietary Bacillus subtilis protects against hepatic failure, and antioxidative suppression induced by ochratoxin A in Thinlip Mullet (Liza ramada) (Magouz et al., 2022).

of mycotoxins in liver and musculature, and histopathological assessment of liver and kidney tissues (Zahran et al., 2020).

CONCLUSIONS Toxigenic secondary fungal metabolites, known as mycotoxins, are regarded as a threat to human health and food safety.

Due to their presence in a wide range of agricultural and food products, they continue to pose a serious threat to the health of animals and humans alike.

This article summarizes the major mycotoxins and their impact on animal and human health. In addition to this, methods used to decontaminate feed and feedstuffs are briefly discussed.

Establishing a strategy for regular analysis and monitoring of mycotoxins levels to ensure food safety is essential for the future.

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