Tenuazonic acid most frequent mycotoxin detected in Asian livestock blood

Thursday, April 15, 2021

Tenuazonic acid most frequent mycotoxin detected in Asian livestock blood




Alternaria mycotoxins

Fusarium and Aspergillus mycotoxins are often considered the most common and critical mycotoxins in grains and feed. However, Alternaria fungi, where the most predominant is A. alternata, have also a large presence in wheat, sorghum and barley, and have also been reported to occur in oilseeds such as sunflower and rapeseed, tomato, apples, citrus fruits, olives and several other fruits and vegetables (EFSA, 2011). Furthermore, some recent feed surveys pointed out the massive detection of Alternaria mycotoxins in feed and evoked increased attention to them in the last few years (Novak et al., 2019; Koshal et al., 2019). Alternaria species produce more than 70 phytotoxins and some of them have been chemically characterized as mycotoxins to animals. The most important Alternaria mycotoxins due to their harmful effects are alternariol, alternariol monomethyl ether and tenuazonic acid (Ostry, 2008) (Figure 1). These Alternaria mycotoxins are described to induce harmful effects in animals including fetotoxic and teratogenic effects. Alternaria mycotoxins are also well known to have estrogenic activity, thus, some Alternaria mycotoxins and several phase I and II metabolites of them are able to bind and activate estrogenic receptors because they act as mimetic of 17-β-estradiol (Lehmann et al., 2006; Dellafiora et al., 2018). Hence, due to their possible harmful effects, Alternaria toxins are of concern for animal health and performance. But, although Alternaria toxins have a significant toxicity, relevant in vivo toxicological data are scarcely available.



Tenuazonic Acid

Among Alternaria toxins, tenuazonic acid is considered the most toxic (Asam and Rychlik, 2013) and most frequent detected in feed samples. Several surveys have shown the larger presence of tenuazonic acid comparing to other Alternaria mycotoxins. For instance, tenuazonic acid was detected in 55% of feed samples (n = 1,141) with a mean concentration of 255 µg/kg, by contrast, alternariol was detected in 50% of swine feed samples with an average concentration of 17 µg/kg and alternariol monomethyl ether was detected in 40% of the samples with an average concentration of 6 µg/kg (Novak et al., 2019). Furthermore, in a similar feed survey study tenuazonic acid was detected in 73% of swine feed samples (n = 526) while alternariol and alternariol monomethyl ether were detected in 70 and 59% of the samples respectively (Koshal et al., 2019). Moreover, tenuazonic acid has normally the highest concentration detected among Alternaria mycotoxins. For example, while contamination levels of Alternaria mycotoxins in grains were <100 µg/kg and maximum concentrations were <1,000 µg/kg, the maximum observed tenuazonic acid contamination level in cereals was 4,224 µg/kg (Fraeyman et al., 2017). All this data allows to confirm, without a doubt, that tenuazonic acid is among Alternaria mycotoxin the most frequent and it has the highest concentration in feed. What is more, mentioned feed surveys also permitted to demonstrate that tenuazonic acid presence is more frequent than other extensively analysed mycotoxins as Fumonisin B1 or T-2 toxin (Koshal et al., 2019).

Therefore, interest for tenuazonic acid increased recent years when feed and food surveys could reveal the large presence of this mycotoxin. For this reason, studies to evaluate toxicity of tenuazonic acid started to be performed, but the knowledge about tenuazonic acid toxicity is still scarce. In vitro studies are limited, however, it has been discovered that presence of tenuazonic acid stops the formation of new proteins blocking the liberation of them from the ribosomes (Shigeura et al., 1963). On the other hand, in vivo studies demonstrated that exposure to tenuazonic acid has more severe effects. Tenuazonic acid caused emesis, salivation, tachycardia, haemorrhages and haemorrhagic gastro-enteropathy in several animal species as chicken, rats and dogs. Moreover, it is well known the large impact of tenuazonic acid in intestinal tissues (Fraeyman et al., 2017). Thus, a sub-acute exposure to tenuazonic acid produces intestinal multi-haemorrhages in poultry species and it results in the presence of bloody diarrhoea (Fraeyman et al., 2017). Moreover, exposure to tenuazonic acid has been linked to erosions of the gizzard and mottled spleens. Tenuazonic acid also impairs liver and kidney as microscopic exploration detected congestion of blood vessels and haemorrhages in kidneys and livers from poultry species exposed to tenuazonic acid. Besides, a chronic exposure to tenuazonic acid also reduced animal performance as reduction in the weight gain of broilers exposed to tenuazonic acid was also observed (Giambrone et al., 1978). So, although toxicity of tenuazonic acid is still not very well known, there is no doubt that exposure to this Alternaria mycotoxins has a huge impact in animal health status and performance.


Assessing real exposure to Tenuazonic acid through blood analysis

Feed surveys helped to identify tenuazonic acid as a big threat for livestock as they detected the large incidence and concentration of it in feed. Nonetheless, feed surveys are not able to elucidate the real mycotoxin exposure specifically for each farm. Recent analytical advances allowed to develop methods to determine mycotoxin biomarkers in blood and they rapidly have been proposed as the successful method to assess the exposure to mycotoxins, specifically for each farm. Thus, Innovad, applying Myco-Marker® service, collected 200 blood samples using FTA cards from Asian farms to elucidate the real mycotoxin exposure. Thirty-six (36) different mycotoxin biomarkers were analysed per sample to determine the real mycotoxins risk and not just the four typical studied mycotoxins (deoxynivalenol, aflatoxin, zearalenone and fumonisins). Surprisingly, blood analyses allowed to see that tenuazonic acid was the most frequent mycotoxin detected in blood. Thus, tenuazonic acid was detected in blood samples from 42% of the studied farms. Although, tenuazonic acid was more detected in blood from swine (60%), it was also persistent in poultry farms (33%). In addition, some worrying concentrations were detected, for instance, a maximum concentration of 100 ng of tenuazonic acid /mL in blood from pig was detected. The tenuazonic acid concentrations quantified in blood indicated specifically moderate/high threat for some farms (~30%) when risk level was established after using toxicokinetic data (Fraeyman et al., 2015). Noteworthy, another Alternaria mycotoxin, alternariol monomethyl ether, was also detected in blood samples. So, obtained results permitted to identify the large exposure of livestock to Alternaria mycotoxins, with tenuazonic acid as the principal threat, specifically for each farm. Moreover, analyses revealed that animals were always exposed to three or more mycotoxins in all studied farms from Asia (Figure 2) and this is of concern as co-exposure to other mycotoxins have a synergistic or additive negative toxic effect. These results are, without a doubt, demonstrating that mycotoxin control strategies cannot be only focused in the main four mycotoxins (zearalenone, deoxynivalenol, fumonisins and ochratoxin A), other commonly no controlled mycotoxins as tenuazonic acid or other emerging mycotoxins, as beauvericin or enniatins, can represent a greater threat than the main four mycotoxins. This means that real mycotoxin impact can not be totally known if the most frequent mycotoxins as tenuazonic acid or emerging mycotoxins are not controlled. For this reason, it is important to control the real mycotoxin levels to optimize mitigation strategies to reduce mycotoxins impact and improve animal performance.



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Article made possible through the contribution of Innovad