THE ALLEVIATION OF OXIDATIVE STRESS, A KEY STRATEGY TO MITIGATE THE IMPACT OF DEOXYNIVALENOL ON ANIMAL HEALTH

BIŌNTE QUIMITŌX PLUS is an effective anti-mycotoxins solution to combat the severe mycotoxins challenge related to oxidative stress.

The presence of mycotoxins in animal nutrition poses several problems for animal health and performance parameters. Mycotoxins binders are included in feed to counteract the negative effects of these toxins. This strategy aims to adsorb and excrete certain families of mycotoxins, reducing their bioavailability and minimizing their harmful effects on animals. However, due to the diversity in their chemical structures, the adsorption efficacy differs between mycotoxins. In this scenario, most of the mycotoxins binders used have low efficacy for deoxynivalenol (DON), a common mycotoxin in raw materials and feed that generates significant economic losses.

DON induces oxidative stress at cellular level

DON, also known as vomitoxin, is a trichothecene produced by fungi of the genus Fusarium. It is one of the most common mycotoxins found in cereals and their by-products worldwide. Its presence is particularly notable in corn, wheat and oats (EFSA, 2013; Gruber-Dorninger et al., 2019). Among the toxic effects observed after DON exposure, the decrease in feed intake, alterations in the intestinal and hepatic functions of the organisms, as well as immunomodulation stand out. These effects compromise the performance parameters and the animal health (Riahi et al., 2020; You et al., 2021). It is important to highlight that DON toxicity is closely related to the induction of oxidative stress (Mishra et al., 2014)

Oxidative stress is defined as the imbalance between free radicals (ROS) and the antioxidant mechanisms of the organism. Thus, DON-induced increase in ROS levels leads to oxidation and damage to DNA and lipids, causing apoptosis (cell death) and alterations in the metabolism of the animals (You et al., 2021).

Phytogenic extracts: a complementary strategy to mitigate the negative effects of DON

In such situations, the use of phytogenic ingredients is of great interest due to their extensive range of beneficial effects. Thus, in order to mitigate the negative effects of mycotoxins, BIŌNTE has developed QUIMITŌX® PLUS: a complete anti-mycotoxins solution that includes extracts rich in silymarin and curcumin in its formula.

Silymarin and curcumin, how can they reduce the negative effects of DON?

Silymarin

In the case of trichothecenes, such as DON, it has been observed that their transport into cells is carried out mainly by facilitated transport. In cells highly affected by the presence of DON, such as hepatic and intestinal cells, DON entry occurs primarily through channel proteins, such as the organic anion transporting polypeptide (OATP) family. In this scenario, silymarin acts as an inhibitor of the OATP, preventing the entry of DON into hepatic and intestinal cells, thus protecting the cells from the harmful effects of this mycotoxin (Xiaoming et al., 2017).

Curcumin

On the other hand, the curcumin-rich extract shows multiple antioxidant effects and plays an essential role in reducing cellular oxidative stress: it can eliminate high levels of free radicals, such as superoxide anions, hydroxyl radicals and nitric oxide, which are observed in the cellular redox imbalance. Likewise, various studies have shown that dietary supplementation with curcumin increases the expression of the Nrf2 transcription factor and the activity of endogenous antioxidant enzymes, such as glutathione (GSH), catalase (CAT) and superoxide dismutase (SOD). In addition, curcumin inhibits the activation of the mitogen-activated protein kinase (MAPK) signalling pathway, reducing ribotoxic stress (Hafez et al., 2022), the main toxic pathway of DON at the cellular level. Thus, curcumin reduces the DON toxicity. In addition, it can improve mitochondrial antioxidant capacity by increasing mitochondrial membrane potential, thereby reducing mitochondrial dysfunction and hepatic cell apoptosis, thus contributing to alleviate liver damage (Pan et al., 2022).

In vitro efficacy of BIŌNTE® QUIMITŌX® PLUS to mitigate the negative effects of oxidative stress induced by DON

Recently, the results of an in vitro study, carried out in collaboration with the Biotech Agrifood Laboratory of the University of Valencia (Spain), have demonstrated the efficacy of BIŌNTE® QUIMITŌX® PLUS to mitigate the oxidative stress induced by DON in hepatic cells, of great interest due to the great metabolic importance of the liver.

The study was performed in HepG2 cells using the dichlorodihydrofluorescein-diacetate (H2-DCFDA) test to determine intracellular levels of ROS by fluorescence. The use of 1 kg/t of QUIMITŌX® PLUS was evaluated against the exposure to three concentrations of DON (1, 2 and 4 ppm) at several time-points, from 5 min to 24 h.

Considering the DON toxicokinetics in broilers, the ROS levels detected in hepatic cells after 15 min of exposure to DON (1, 2 and 4 ppm) and the inclusion of QUIMITŌX® PLUS at 1 kg/t are presented below.

The in vitro assays in hepatic cells show that the use of BIŌNTE® QUIMITŌX® PLUS at 1 Kg/t in DON-contaminated media at different doses produces a clear decrease in ROS levels after 15 min of exposure.

On the other hand, considering the toxicokinetics of the mycotoxin in pigs, the ROS levels detected in hepatic cells after 2 h of DON-exposure (1, 2 and 4 ppm) and the inclusion of QUIMITŌX® PLUS at 1 kg/t are presented below.

The results demonstrate that the use of BIŌNTE® QUIMITŌX® PLUS at 1 Kg/t in DON-contaminated medium at different doses produces a clear decrease in ROS levels after 2 h of exposure.

The presence of mycotoxins in animal nutrition poses significant challenges to animal health and performance parameters. The use of mycotoxins binders and phytogenic ingredients are complementary strategies to mitigate the negative effects of these toxins. However, the diversity of chemical structures and the low adsorption of some mycotoxins, such as DON, pose limitations in the efficacy of conventional adsorbents. In this sense, the use of extracts rich in silymarin and curcumin offers a synergistic effect to protect hepatic from the detrimental effects of mycotoxins, by inhibiting the OATP channel protein and reducing cellular oxidative stress.