Potential Role of Individual and Combined Effects of T-2 Toxin, HT-2 Toxin and Neosolaniol on the Apoptosis of Porcine Leydig Cells

Abstract

T-2 toxin usually co-occurs with HT-2 toxin and neosolaniol (NEO) in the grains and feed. Our previous studies found that T-2 toxin and its metabolites’ binary or ternary combination exposure to porcine Leydig cells (LCs) displayed synergism in certain range of dosage and cannot be predicted based on individual toxicity. However, the possible mechanism of these mycotoxins’ combined exposure to cell lesions remains unknown. Based on 50% cell viability, the mechanism of apoptosis in porcine Leydig cells was investigated after exposure to T-2, HT-2, NEO individual and binary or ternary combinations. Compared with control, the adenosine triphosphate (ATP) content decreased, reactive oxygen species (ROS) level increased, and mitochondrial membrane potential (MMP) decreased in all treated groups. Additionally, the cell apoptosis rates were significantly increased in test groups (p < 0.05), and the B-cell lymphoma 2 (Bcl-2) Associated X (Bax)/Bcl-2 ratio and the expression of caspase 3, caspase 8, cytochrome c (Cytc) in the treated group are all significantly higher than the control group. Moreover, the expression of Cytc and caspase 8 gene in NEO and T-2+NEO groups was significantly higher than that in other individual and combined groups. It can be concluded that the toxicities of T-2, HT-2, and NEO individually and in combination can induce apoptosis related to the oxidative stress and mitochondrial damage, and the synergistic effect between toxins may be greater than a single toxin effect, which is beneficial for assessing the possible risk of the co-occurrences in foodstuffs to human and animal health.

Deciphering the Hazardous Effects of AFB1 and T-2 Toxins: Unveiling Toxicity and Oxidative Stress Mechanisms in PK15 Cells and Mouse Kidneys

“…In vitro, PK15 cells were treated with a combination of AFB1 and T-2 to evaluate their toxicity and oxidative stress responses. The findings of this study revealed that AFB1 and T-2, alone or in combination, produced time-and dosage-dependent increasingly toxic effects on PK15 cells, which is similar to the effects of T-2 toxin and its metabolites observed on porcine Leydig cells [28]. Our initial findings revealed that, at equivalent doses, cell viability in the T-2 group was significantly lower than in the AFB1 group (Figure 1A,B), indicating that T-2 had a more pronounced effect on cell viability at the same concentration.…”

“…In Vero kidney cells, AFB1 and OTA not only showed an additive cytotoxic effect but also synergism to promote genotoxicity with increased DNA fragmentation [ 31 ]. There experiments indicate that the binary and ternary combinations of T-2, HT-2, and NEO displayed synergistic toxicity in porcine Leydig cells [ 28 ]. However, it should be noted that differences in cell model, toxin concentration, and incubation time may affect the effects of toxin combinations.…”

The sweating process promotes toxigenic fungi expansion and increases the risk of combined contamination of mycotoxins in Radix Dipsaci

“…Additionally, there may be antagonistic, additive, and synergistic effects among mycotoxins. For instance, the combination of AFB 1 and OTA can enhance its toxicity ( McKean et al, 2006 ; Xu et al, 2022 ). The combination of AFB 1 and T-2 increases their toxicity ( Hou et al, 2018 ; Xiao et al, 2023 ).…”

Toxicodynamic of combined mycotoxins: MicroRNAs and acute‐phase proteins as diagnostic biomarkers

“…Different indicators present different combined effects, resulting in reproductive toxicity (Alahmar, 2019). When exposed to the two toxins for 3 and 5 days, the mouse brain experiences a significant induction of oxidative stress and apoptosis, synergistically enhancing brain damage (Xu et al., 2022). However, urine metabolomics analysis has revealed an antagonistic toxic effect on the metabolism of mice when DON (2 mg/kg) and ZEA (20 mg/kg) are combined (Shi et al., 2018).…”

“…Several physiological mechanisms are in place to maintain homeostasis. Factors such as infection, exposure to various compounds, including AFB1, and physical or thermal tissue injuries can trigger a complex early systemic reaction known as the APR (Xu et al., 2022). The APR plays a crucial role in ensuring survival during the immediate aftermath of an injury.…”