Table 3.
Examples of combined mycotoxins effects disturbing metabolic and immune reactions (focusing on low concentrations).
| Mycotoxin | Effective dose, target | Effect | Major conclusion | References |
|---|---|---|---|---|
| AFB1/ AFM1 | 5–30 μM, murine macrophage | ↓ NO production by LPS-stimulated macrophages | Alteration of immune response and ↓defense ability against tumorgenesis | (73) |
| AFB1/ AFB2/ AFG1/ AFG2 | 1.0, 0.5, 0.25, and 0.25 ng/mL (respectively), bovine PBMCs | ↑ TLR-4 mRNA expression level | Signal transduction by TLRs | (74) |
| AFB1/ AFB2/ AFG1/ AFG2 | 2.0, 1.0, 0.5, and 0.5 ng/mL (respectively), porcine monocyte-derived DCs | ↑ Expression of co-stimulatory molecules; CD25 and CD80/86 ↑ Antigen-presenting capacity of DCs |
Breakdown of immunological tolerance | (75) |
| AFB1/ AFB2/ AFB2a/ AFG1/ AFG2/ AFM1 | 0.1, 1, and 10 pg/mL, rat macrophage | ↓ Phagocytosis activity ↓ Intracellular killing and spontaneous superoxide production (The biggest effect by AFB1 and AFM1 The smallest effect by AFG1) |
Depressive effect on macrophages and a susceptibility of host to infectious diseases | (76) |
| AFB1/ OTA/ FB1/ T-2 | 1, 3, 10, and 30 μM, human Caco-2 cell | ↓ mRNA expression of the tight junction proteins (claudin-3 and occludin) | ↑ Paracellular (epithelium) permeability | (77) |
| AFB1/ OTA/ FB1 | OTA and AFB1 (5 and 40 ng/mL) FB1 (5 and 40 μg/mL), human mononuclear blood cells | ↑ DNA damage and fragmentation ↑ Cell apoptosis ↓ Cell viability |
Increased immuno-suppression by chronic exposure, especially in patients with chronic diseases, like cancers, tuberculosis, malaria, and HIV | (78) |
| OTA/ FB1 | OTA (5 ng/kg b.w.) FB1 (200 ng/kg b.w.), rat kidney and liver |
↑ MDA and Protein carbonyls ↓ CAT activity |
High potential to induce oxidative damage | (79) |
| 0.05, 0.5 and 5 μg/mL, porcine kidney epithelial cells | ↑ Lipid peroxidation ↓ GSH level ↓ Cell viability |
Long-term exposure is an important inducer of immunosuppression and development of chronic renal diseases | (80) | |
| FB1/ DON | FB1 (110 μg/kg b.w./day) DON (45 μg/kg b.w./day), mice | ↑ Triglyceride and total cholesterol ↑ Blood total proteins and creatinine ↑ m5dC level from 3.6 to 7.2% (DNA methylation) ↑ DNA fragmentation |
Lipid and lipoprotein (increased serum proteins) metabolism disorders Blood lymphocytes cell deaths | (81) |
| 3+6 mg/kg, piglet | ↓ The number of goblet cells ↑ The number of lymphocytes, plasma cells, and eosinophils ↓ Lymphocytic infiltration ↓ Epithelial cell proliferation ↑ TNF-α, IL-1β, IFN-γ, IL-2, IL-6, IL-12p40, MIP-1β, and IL-10 expression in ileum or jejunum (alone) ↓ Adherent junction protein E-cadherin and occludin in the intestine |
Alteration in the intestine and induction of more susceptibility to infections by enteric pathogens | (82) | |
| DON/ ZON | 40+12 μg/kg, porcine peripheral blood lymphocytes | ↓ CD4+ and CD8+ lymphocytes | Transiently depletion of immunoregulatory mechanisms (strong effects of mixed AFs) | (83) |
AFB1, aflatoxin B1; NO, nitric oxide; LPS, lipopolysaccharides; PBMCs, peripheral blood mononuclear cells; TLR, toll-like receptor; DCs, dendritic cells; OTA, ochratoxin A; FB1, fumonisin B1; HIV, human immunodeficiency virus; MDA, malondialdehyde; CAT, catalase; GSH, glutathione; DON, deoxynivalenol; m5dC, 5-methyldeoxycytidine; TNF-α, tumor necrosis factor-alpha; IL-1β, interleukin 1β; IFN-γ, interferon-gamma; MIP-1β, macrophage inflammatory protein 1-beta; ZON, zearalenone; CD4, cluster of differentiation 4.