Ochratoxin A Toxicosis in Economic Animal Production

1. Introduction

Ochratoxins are a group of widespread toxic secondary metabolites produced by A. niger, and Penicillium verrucosum fungi commonly found in cereal (e.g., wheat, soybeans, and coffee beans), nuts, fruits (grapes), and animal feed [1,2]. Ochratoxins incidence highly occur in South Asia, Eastern Europe, and Sub-Saharan Africa, where the climatic conditions are warm and wet, favoring the growth of toxigenic fungi [3,4]. There are twenty different types of ochratoxins, among which ochratoxin A (OTA) is the highest occurrence and most toxic for non-ruminants and humans, especially for poultry and pigs [5,6]. Ochratoxin A consists of a dihydroisocoumarin part coupled, via its 7-carboxy group, with an L-β-phenylalanine part [7]. Ochratoxin A has strong thermal stability, which induces this mycotoxin to be challenging to remove by feed processing [8]. Besides, OTA has high bioaccumulation efficiency in animal tissues, organs, and dairy products and is transferable over the food chain [9]. Furthermore, OTA often occurs with fumonisin B₁(FB₁) and aflatoxin B₁ (AFB₁) because they have similar toxigenic temperature and humidity conditions. Different studies explain that OTA and FB₁, or OTA and AFB₁ when given in combination, have synergistic effects on each other, causing aggravated adverse effects mainly present in nephrotoxicity in poultry and pigs [10]. In summary, feed contamination with OTA is a problem almost exclusively for monogastric livestock, mainly due to the economic losses caused by the reduction of production performances, the negative impact on animal health, and the food safety issues due to the transfer of the toxin through the food chain to humans [7].

2. Toxicities on Animal Production

Phenylalanine is a key moiety for OTA toxicity. This chemical structure induces phenylalanine tRNA synthase dysfunction and acts as a competitive inhibitor of carboxypeptidase A [11], which inhibits protein synthesis and furthers a series of toxicities and symptoms in animals [1,12,13]. Ochratoxin A is a nephrotoxin and a hepatotoxin, immune suppressant, potent teratogen, and carcinogen which induces poor growth performances and low egg quality in pigs and poultry [1,14]. Due to ruminal bacterial protection, ruminants have a higher tolerance to OTA than monogastric animals (e.g., pigs and poultry); among monogastric animals, birds are more sensitive than swine because of the former’s renal metabolic process. Typically, young animals are more sensitive to OTA than mature ones due to their incomplete organ development [15]. 

Nephrotoxicity is considered the most important toxicity of OTA in all the non-ruminant mammals tested so far, as well as in poultry [16]. The feed containing higher OTA concentrations has been conformed to provoke porcine spontaneous nephropathy in Bulgaria and South Africa [17,18]. For about four months, porcine feed containing more than 200 μg/kg of OTA induces nephropathy damage during the fattening period [19]. Chronic exposure to OTA in birds reduces urine quantity, phenol clearance, and impaired glomerular and proximal tubular infiltration [20]. It also affects the renal functional ability to metabolize calcium and causes lipid peroxidation in poultry [21]. In addition to the kidney, the liver is the organ most severely affected by OTA, and histological alterations include congestion, swelling, and tissue lesions [22].

Ochratoxin A accumulates in the organs and products of animals due to its high protein affinity, especially to albumin, and causes contamination carryover [13,23]. In many countries, OTA was reported in samples of muscle, milk, and eggs [24,25]. Besides, due to the high accumulation of OTA, chronic exposure to it in low doses may have higher toxicity than acute exposure in high doses for animals [26].

Table 1. The guidance values of the European Union (EU) Commission and China for ochratoxin A concentrations (μg/kg) in complete feed [27-29].

2.1  Swine

Swine is the more susceptible animal to OTA exposure as compared to ruminants. Ochratoxin A is nephrotoxic, hepatotoxic, immunotoxic, teratogenic, and neurotoxic in each stage of swine [30,31]. Ochratoxin A-acute toxicity affects the kidneys most, causing nephropathy by damaging proximal tubules in pigs [17]. Ochratoxin A is considered to be the most important mycotoxin provoking mycotoxic porcine nephropathy (MPN) [32], which is a widely encountered renal disease all over the world, such as famous Danish porcine nephropathy and Bulgarian porcine nephropathy [17,18]. The porcine gastrointestinal tract absorbs 65% of OTA after consuming the OTA-contaminated feed [33], and OTA accumulation occurs in several tissues (primarily in kidneys), leading to clinical symptoms, such as depression and reduction in feed intake, with consequent body weight loss, followed by dehydration, diarrhea, polyuria, and polydipsia, ultimately to death [34,35]. The equation slope from review research indicates an average reduction of 12% in weight gain of pigs for an increase of 1 mg/kg of OTA in the diet [7]. After necropsy of sick pigs, it will be found that enlargement of renal lymph nodes, neoplastic changes, significantly enlarged and pale appearance of kidneys as well as fibrotic changes in the cortex of the kidneys [36]. 

For reproductive ability, OTA with high concentration affects sperm production and boar semen quality [37], on the contrary, the reproductive tract of sows showed no obvious abnormalities either in the adult or the embryo [38]. Moreover, OTA also alternates some metabolism and is revealed by several anomalous serum blood parameters such as hyperproteinemia, azotemia, hypocholesterolemia, and hypercalcemia, which may indirectly affect growth performance and production ability in swine [39]. Besides, OTA induces immunosuppression, making Brachyspira hyodysenteriae and porcine circovirus type 2 (PCV2) infections in pigs [40]. 

It should be noted, because of the stability of OTA and its long half-life in blood and tissues, pigs ingesting feed containing OTA causes the latter to remain in pork and some edible tissues of pigs [14]. This may represent a potential danger to the human food chain. Indeed, the occurrence of OTA in lard, pork, blood, and liver has been extensively documented as well [14,41]. 2 

Table 2. Toxic concentrations and symptoms of ochratoxin A (OTA) in pig

2.2  Poultry

Ochratoxin A is one of the most toxic mycotoxins in poultry, which is more sensitive than swine [45,46]. Poultry has a lower absorption rate for OTA, which can be carried to the hindgut (mainly in the proximal jejunum) and alter with beneficial intestinal microbiota [47]. Previous research indicated that the populations of the beneficial species Lactobacillus declined in chickens exposed to OTA [45]. Besides, OTA reduced the abundance of cecum microbiota in ducks, particularly Bacteroides, and triggered intestinal injuries [48]. The physiological symptoms of OTA toxicity in poultry are weakness, anemia, reduced feed consumption, decreased productivity, reduced egg-laying, poor feathers, and excessive mortality at high dietary concentrations [49,50]. Although OTA induces alterations in internal organs such as pale swollen kidneys and enlarged yellowish livers in poultry [1,51], however, OTA is more a nephrotoxin than a hepatotoxin for poultry [52]. Nephrotoxicity of OTA also directly affects these adverse effects on production performance in broiler and laying hens.

Poultry exposed to OTA-contaminated feed becomes more prone to parasitic diseases and secondary bacterial infections, and this happens due to immunosuppression along with nephrotoxicity induced by OTA [53]. A previous study reported an increased incidence of acute enteritis in birds given OTA-contaminated feed [54]. Poultry feed containing OTA also increases the chances of air sacculitis as a secondary infection of E. coli in turkeys [55]. The immunosuppression, growth reduction, and other OTA-associated alterations make the poultry more compromised and prone to other bacterial infections. In such cases, the secondary infections become much more aggravated than those observed in birds receiving feed without OTA. Previous scientists reported an enhanced Salmonella infection when co-administered with OTA [56]. Similarly, OTA administration in birds also aggravates different viruses induced infections, as observed alongside the inclusion body hepatitis (IBH) virus [57].

Regarding reproductive toxicities, teratogenic effects were reported in many animal studies, including chicks and quails with craniofacial abnormalities and reduced birth weight being the most common [5,38]. It has been observed with great concern that eggs laid by the hens fed on OTA-contaminated feed contain their residues which are severe threats to developing embryos as these residues can cause embryonic deaths [58], reduced hatchability percentage, and poor performance/immune status of those hatched. 

Table 3. Toxic concentrations and symptoms of ochratoxin A (OTA) in poultry

2.3 Ruminants 

Ruminants (such as cattle, sheep, and goats) are able to degrade OTA to the virtually non-toxic ochratoxin α (OTα) in the rumen mainly through the action of protozoa, thus rendering acute poisoning an infrequent event under field conditions [7,63]. An in vitro experiment concluded that cows may degrade OTA in feeds contaminated with up to 12 mg/kg [64]. Such high levels of OTA are extremely rare in the diets of general ruminant farms. In some extreme experiment conditions, higher doses of OTA (e.g., 13 mg/kg) produced clinical symptoms (e.g., anorexia, diarrhea, and difficulty in rising and rapid decrease of milk production), while the lower dose of OTA ranging from 0.2 to 1.66 mg/kg showed no clinical symptoms [65]. However, such ability is strictly related to rumen functionality. According to some experiment results, the ability of sheep to degrade OTA in its rumen is lower than that observed in cattle. Besides, pre-ruminating calves are more sensitive to OTA toxicities because they lack a developed rumen with a functional microbial population [15], thus leading to the death of calves within 24 hours from an administration by a stomach tube of a single dose of 11 mg OTA/kg body weight [16,66]. Besides, intravenous infusion of OTA at 1 mg/kg of body weight caused the death of ewes within 24 hours [7,67]. Even though ochratoxicosis has been rarely reported in ruminants, the long-term accumulation of OTA in blood and tissues represents a potential risk of its harmful effects in cattle. Therefore, the best way to prevent the adverse effects of OTA is to minimize its intake in ruminant production. 

Table 4. Ochratoxin A (OTA) toxicities on growth performance in ruminants

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