Table 4.
The cardiotoxicity of mycotoxins.
| Mycotoxin | Effective dose, target | Effect | Major conclusion | Ref. |
|---|---|---|---|---|
| OTA | 289 μg/kg, myocardial tissue of rat | Histopathological changes on myocardial tissue; Extensive cytoplasmic vacuole formation Necrosis of the myocytes Dissolution of the nucleus Clumped fibers Fibrinolysis Swollen myocardial fibers Small hemorrhagic areas and hyperaemic vessels |
Heart damage (reduced by the antioxidant effect of melatonin) | (135) |
| 0.1 mL of OTA 5 mg/kg b.w., mice | ↓ Heart weight and rate ↓ SOD, CAT, and GSH ↑ Cardiac enzymes (CK, CK-MB, and LDH) ↑ MDA level ↑ Keap1, Bax, caspase 3 and 9 expressions level ↓ Nrf2, HO-1, and Bcl-2 expression level |
Myocardial injury; mitochondria-mediated apoptosis pathway; (protection by Keap1-Nrf2 signaling pathway) | (136) | |
| T-2 | 0.5 ng/mL, murine embryonic stem cells (embryoid bodies) | ↑ ROS accumulation ↑↓ Phosphorylation of p38 (time-dependent) ↓ Mitochondrial number ↓ Mitochondrial biogenesis-related proteins (PGC-1α, NRF-1, mtTFA, and COXIV) |
Inhibition of cardiac differentiation; via p38MAPK- and ROS-mediated mitochondrial pathway | (137) |
| 0.23 mg/kg, cardiac tissue of rat | Cardiac histopathology; Myofibril degeneration Hemorrhages Glycogen distribution Accumulation of neutrophils, macrophages and mast cells Mast cells degranulation |
Progressive myocardial injuries (cardiomyocytes' lysis and loss of cross-striation) by long exposure (28–60th day) | (138) | |
| 0.125 and 0.25 (-1) μM, primary cardiomyocytes of rat | Autophagy induction; ↑ LC3-II and Beclin-1 levels ↓ Cardiomyocytes viability ↑ LDH release ↑ Cleaved caspase 3 ↑ ROS generation ↓ GSH level and SOD activity (significant with lower dose: 0.125) ↑ MDA level (significant with lower dose: 0.125) ↓ Na+-K+-ATPase activity and Ca2+-Mg2+-ATPase activity ↑ GRP78, CHOP, and p-eIF2α mRNA levels (ER-stress) |
Antioxidant (selenium) deficiency decreases autophagy activity protecting cardiomyocytes and aggregates cardiomyocyte injury through ER stress | (139, 140) | |
| T-2/ DON | 6.0×10−6 and 6.0×10−5 μM (T-2) 0.39 and 0.78 μM 1.56 and 3.13 μM (DON), primary cardiomyocytes of rat | Inhibition of ATP-linked OCR Inhibition of bioenergetics reserve capacity |
Inhibition of mitochondrial ETS function associated with oxidative stress in cardiomyocytes | (141) |
| ZON, α- and β-ZOL | 20-100 μM, H9c2 cell line (embryonic rat heart) | Autophagy induction; ↑ LC3-II and Beclin-1 levels (before the onset of apoptosis) Activation of the mitochondrial apoptotic pathway ↑ ROS generation Loss of mitochondrial transmembrane potential (ΔΨm) Caspases activation Increased cell death |
Higher level of ROS and oxidative stress by long-term exposure (24 h) to ZON and its derivatives overcomes a cardioprotective mechanism (SIRT1-mediated autophagy) | (142) |
OTA, ochratoxin A; SOD, superoxide dismutase; CAT, catalase; GSH, glutathione; CK, creatine kinase; CK-MB, creatine kinase isoenzyme; LDH, lactate dehydrogenase; MDA, malondialdehyde; Bax, Bcl-2-associated X; Nrf2, nuclear factor erythroid 2-related factor 2; HO-1, heme oxygenase 1; Bcl-2, Bcl-2, B-cell lymphoma 2; ROS, reactive oxygen species; PGC-1α, peroxisome proliferator-activated receptor coactivator-1 alpha; NRF-1, nuclear respiratory factor 1; mtTFA, mitochondrial transcription factor A; COXIV, mitochondrial respiratory chain complex IV; p38MAPK, p38 mitogen-activated protein kinase; LC3-II, microtubule-associated protein light chain 3 II; ATPase, adenosine triphosphatase; GRP78, glucose Regulated Protein 78 kDa; CHOP, CCAAT enhancer-binding protein homologous protein; p-eIF2α, phosphorylated α subunit of eukaryotic initiation factor 2; ER, endoplasmic reticulum; DON, deoxynivalenol; OCR, oxygen consumption rate; ETS, electron transport system; ZON, zearalenone; ZOL, zearalenol; SIRT1, sirtuin 1.