Mycotoxins are one of the main feed contaminants worldwide. Mycotoxins exposure can lead to severe effects in animal production, disrupting the intestinal function and integrity, causing liver damage, as well as deleterious immunological impacts. These effects are associated with compromised growth and productivity (da Silva et al., 2016; Pauletto et al., 2020). Since the complete elimination of mycotoxins is impossible, effective mitigation strategies are required (Xu et al., 2022).
Due to their diverse health-promoting properties of their active compounds, natural plant extracts have gained attention to mitigate mycotoxins adverse effects (Qiu et al., 2022; Guerrini et al., 2023).
Curcumin is a natural compound extracted mainly from turmeric (Curcuma longa) and it is used to offer a wide range of benefits on animal health (Pauletto et al., 2020; Pan et al., 2022): It works as an antioxidant, hepatoprotective, anti-inflamatory, antimicrobial, antiviral and antifungal. It also reinforces the intestinal function and promotes the productive performance.
Several studies demonstrate the potential of curcumin to improve the health status of animals. Indeed, it is well known that the phenolic groups contained in curcumin have an essential role to mitigate oxidative stress. Some of these groups can eliminate high levels of ROS (including superoxide ion, hydroxyl radicals and nitric oxides) observed in the redox imbalance at cellular level.
Dietary supplementation with curcumin has been shown to increase the expression of the transcription factor Nrf2 and the activity of endogenous antioxidant enzymes such as glutathione (GSH), catalase (CAT), and superoxide dismutase (SOD), while reducing oxidative enzymes (Hafez et al., 2022). Thus, curcumin can improve mitochondrial antioxidant capacity by increasing the membrane potential, and reducing the mitochondrial dysfunction and the liver cell apoptosis, alleviating the hepatic lesions (Pan et al. 2022).
Additionally, curcumin supports liver function by restoring enzymatic levels of aspartate transaminase (AST) and alanine aminotransferase (ALT). Particularly, in cases of aflatoxicosis, Muhammad et al. (2018) found that curcumin supplementation reduces AFB1 bioactivation in the liver by altering the activity of CYP enzymes. Therefore, curcumin has been shown to mitigate mycotoxin-induced liver damage.
The use of curcumin as immunomodulator agent is increasing as the intestine is the most extensive and complex organ of the immune system. Specifically, curcumin is a natural compound that interacts with different signaling and transcription molecules of the immune system such as mitogen-activated protein kinases (MAPKs), nuclear factor ᴋB (NF-ᴋB) and Janus kinases and STAT proteins (JAK). /STAT). It decreases proinflammatory cytokines (IL-1, IL-6, IL-8, TNF-α, IFN-γ), among other proinflammatory mediators such as inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX2 ) (Kahkhaie et al., 2019). Furthermore, curcumin has been shown to promote intestinal integrity by increasing the tight junction expression and the villi height which, together with the modulation of the microbial population, improves the barrier functions as well as the nutrient digestibility. Thus, curcumin is a natural compound that promotes intestinal health and the productive performance of animals.
These potential properties are promising in challenging mycotoxins scenarios. Thus, Table 1 summarizes the different studies in which the efficacy of curcumin against mycotoxins has been evaluated, observing a potent antioxidant activity accompanied by a hepatoprotective and intestinal health-improving effect.
| Curcumin, doses | Mycotoxin, doses | Target species | Effects of curcumin | Reference |
|---|---|---|---|---|
| 0,4 g/kg | AFB1, 0,02 mg/kg | Broiler chicken | Serum and kidney: restored SOD, CAT, GSH-Px activity | Damiano et al. (2022) |
| 0,4 g/kg | OTA, 2 mg/kg | Duck | Performance: restored BW, BWG, FI and liver weight Plasma: restores SOD and MDA Jejunum: restored GSH-Px, IL-1β, TNF-α, and improves SOD levels affected by OTA Increases villus height and restores Caspase-3 | Ruan et al. (2019) |
| 7,4 and 740 g/L | ZEN, 4,78, 9,5, 19,1 g/L | In vitro - pig cells | Restored ROS levels and relative expression of SOD1, CAT, GPx1 reduced by ZEN | Qin et al. (2015) |
| 0,45 g/kg | AFB1, 5 mg/kg | Broiler chicken | Performance: restored BW and liver weight Serum: restored ALT, ASP, ALP, GGT, SOD, MDA activities Liver: inhibits CYP enzymes-mediated bioactivation of AFB1, upregulates Nrf2, and enhances GST activity | Muhammad et al. (2018) |
| 5 mg/kg | AFB1, 0,2 mg/kg | Nile Tilapia | Performance: restored BWG, and survival rate Plasma: restores SOD, IL-1β, TGF-β and CYP1A | Mahfouz et al. (2015) |
| 0,4 g/kg | OTA, 2 mg/kg | Duck | Serum: reduced ALT activity increased by OTA and restores lipid metabolism Liver: restored SOD and CAT activity, as well as MDA levels. Improved expression of FAS, PPARG and SREBP-1c Cecum: recovered the microbiota disturbance caused by OTA | Zhai et al. (2020) |
AFB1: aflatoxin B1; OTA: ochratoxin A; ZEN: zearalenone; BW: body weight; BWG: body weight gain; FI: feed intake; ROS: reactive oxygen species; SOD: superoxide dismutase; CAT: catalase; GPx: glutathione peroxidase; MDA: malondialdehyde; ALT: alanine transaminase; AST: aspartate transaminase; ALP: alkaline phosphate; GGT: gamma-glutamyl transferase; GST: glutathione S-transferase; TGF–β: transforming growth factor beta; IL-1β: interleukin 1β; TNF-α: tumor necrosis factor; CYP: cytochrome; Nrf2: nuclear factor, erythroid 2 like 2; FAS: fatty acid synthase; PPARG: peroxisome proliferator activated receptor gamma; SREBP-1c: sterol regulatory element binding transcription factor1.
Silymarin is a complex flavonoid found in the milk thistle (Silybum marianum): contains a mixture of flavonolignans and flavonoids characterized by having several beneficial properties for health such as antioxidant, hepatoprotective, immunostimulant, and barrier function-promoting activity. For years, silymarin has been considered a promising natural compound to protect the liver from different toxic substances and to mitigate consequent liver damage (Wadhwa et al., 2022).
It has been observed that the supplementation of silymarin in the diet restores the level of functional enzymes of the liver such as γ-glutamyl transferase (GGT), aspartate transaminase (AST), alanine aminotransferase (ALT) and alkaline phosphatase (ALP). Additionally, silymarin modulates the expression of caspases, transmembrane glycoproteins (n-cadherin) and chemokines, among other proteins, responsible for cell viability and tissue integrity, as well as the local immune response.
As described in the case of curcumin, the use of a natural agent such as silymarin interacts with different signaling and transcription molecules of the immune system such as kinases (including p38 MAPK) and the factors NF-ᴋB and STATS. Silymarin reduces the levels of proinflammatory cytokines (such as IL-1β, IL-2, IL-10, TNF-α, IFN-γ, TGF-β) and promotes the anti-inflammatory effect (Agarwal et al., 2006).
On the other hand, it is important to highlight that the hepatoprotective function is supported by the regulation of the lipid metabolism. It is used to reduce the triglyceride, cholesterol levels, and the redox balance between the activity of endogenous antioxidant enzymes and free radicals. Additionally, the use of silymarin has been shown to reduce liver damage at the microscopic and macroscopic levels.
Regarding the intestinal barrier, silymarin supplementation increases the absorption surface and modulates the intestinal microbiota, which, in turn, results in an improvement in digestibility, growth and product quality (meat and eggs). It also enhances lipid profile, among other parameters.
Table 2 shows the different studies that have evaluated the efficacy of silymarin in animal nutrition under the challenge with mycotoxins, highlighting its beneficial effects on the liver.
| Silymarin, dosis | Micotoxinas, dosis | Target species | Effects of silymarin | Reference |
|---|---|---|---|---|
| 0.1 g/kg | AFB1, 5µg FB1, 0.02 mg/kg | Broiler chicken | Performance: restored BWG, FCR Serum: restored ALT, AST, and globulin levels Jejunum: increased villus height and crypt depth Meat quality: restored ROS and GST levels, increases PUFA levels, pH and reduces L* values | Armanini et al. (2021) |
| 0,6 g/kg | AFB1, 0.8 mg/kg | Broiler chicken | Performance: restored growth performance | Tedesco et al. (2004) |
| 1-2 g/kg | AF, 2.2 mg/kg | Japanese quail | Performance: restores BWG, FCR Serum: restores ALT, AST, ALP activities, reduces triglycerides and glucose | Khaleghipour et al. (2019) |
| 6 g/kg | OTA, 3 mg/kg | Broiler chicken | Kidneys and liver: restored AST, ALT activities and reduces macroscopic and microscopic lesions | Stoev et al. (2021) |
| 5 g/kg | DON, 4.9 mg/kg ZEN, 0.66 mg/kg | Duck | Liver: reduced MDA and ROS levels, and decreased cytotoxicity | Egresi et al. (2020) |
| 0.6 mg/kg-BW | AFB1, 1 mg/kg-BW | Calve | Performance: restored BWG, FI Blood: restored AST, ALP levels | Nasser et al. (2016) |
BWG: body weight gain; FI: feed intake; FCR: feed conversion ratio; ROS: reactive oxygen species; MDA: malondialdehyde; ALT: alanine transaminase; AST: aspartate transaminase; ALP: alkaline phosphate; GST: glutathione S-transferase; PUFA: polyunsaturated fatty acids.
As a conclusion, the use of curcumin and silymarin have been shown to be able to reduce the toxicity of the mycotoxins in animal nutrition. Their combination is an interesting strategy to synergistically mitigate the immunotoxic and hepatotoxic effects of mycotoxins to promote the animal health and productivity.
In animal production, the use of products based on curcumin and silymarin extracts can enhance the intestinal barrier and the digestive functionality, to improve the immune response, to boost the detoxification capacity of liver cells and to enhance growth, meat and egg quality.
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