T-2 toxin neurotoxicity: role of oxidative stress and mitochondrial dysfunction

Dai, Chongshan; Xiao, Xilong; Sun, Fengjun; Zhang, Yuan; Hoyer, Daniel; Shen, Jianzhong; Tang, Shusheng; Velkov, Tony

doi:10.1007/s00204-019-02577-5

Cited by 114 publications

(53 citation statements)

References 135 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Previous studies demonstrated that CuSO 4 or copper chloride (CuCl 2 ) exposure can induce the production of excessive ROS in HEK293 cells, mouse liver cells or neuronal cells (23,40,41). Mitochondria are not only the major producer of cellular ROS but also a target (42). It has been demonstrated that CuSO 4 exposure can cause mitochondrial dysfunction in neuroblastoma SH-SY5Y cells, and human hepatoma (HepG2) cells (43,44).…”

Section: Figure 7 |mentioning

confidence: 99%

Molecular Mechanisms Underlying Protective Role of Quercetin on Copper Sulfate-Induced Nephrotoxicity in Mice

et al. 2021

Self Cite

View full text Add to dashboard Cite

Copper overload is an established cause of nephrotoxicity, but the precise molecular mechanism remains unknown. Our study aimed to investigate the molecular mechanism of copper sulfate (CuSO4)-induced nephrotoxicity and the protective effect of the natural compound quercetin using a mouse model. Mice were orally administered CuSO4 only (200 mg/kg per day), or co-administered CuSO4 (200 mg/kg per day) plus quercetin (25, 50, or 100 mg/kg per day), or quercetin only (100 mg/kg per day), or vehicle for 28 days. The blood and kidneys were collected for the examination of serum biomarkers, oxidative stress biomarkers, changes in histopathology and gene and protein expression. Our results show that quercetin supplementation attenuates CuSO4-induced renal dysfunction and tubular necrosis in a dose-dependent manner. Quercetin supplementation at 50 and 100 mg/kg significantly attenuated CuSO4-induced oxidative damage. Quercetin supplementation also inhibited the activities of caspases-9 and−3, and the expression of p53 and Bax mRNAs. Furthermore, quercetin supplementation markedly activated the expression of Nrf2 and HO-1 mRNAs, but inhibited the expression of NF-κB, IL-1β, IL-6, and TNF-α mRNAs. In conclusion, our results revealed that quercetin supplementation could inhibit CuSO4-induced nephrotoxicity in mice via the inhibition of mitochondrial apoptotic and NF-κB pathways and the activation of Nrf2/HO-1 pathway. Our study highlights quercetin as a potential candidate in treating copper overload-induced nephrotoxicity.

show abstract

Section: Figure 7 |mentioning

confidence: 99%

Molecular Mechanisms Underlying Protective Role of Quercetin on Copper Sulfate-Induced Nephrotoxicity in Mice

et al. 2021

Self Cite

View full text Add to dashboard Cite

show abstract

“…T2 toxin also shows neurotoxic activity and exposure to this substance results in a wide range of neurological symptoms, such as ataxia, muscular weakness, anorexia, as well as pathological lesions in the brain with disturbances in the functioning of this organ [ 179 , 180 , 181 ]. The main mechanisms underpinning the neurotoxic properties of T2 toxin are connected with reactive oxygen species and oxidative stress, as well as with mitochondrial dysfunction (consisting of the inhibition of the mitochondrial membrane potential and intensification of apoptosis) [ 182 ].…”

Section: Mycotoxins Affecting the Enteric Neuronsmentioning

confidence: 99%

Mycotoxins and the Enteric Nervous System

Gonkowski

Gajęcka

Makowska

2020

Toxins

View full text Add to dashboard Cite

Mycotoxins are secondary metabolites produced by various fungal species. They are commonly found in a wide range of agricultural products. Mycotoxins contained in food enter living organisms and may have harmful effects on many internal organs and systems. The gastrointestinal tract, which first comes into contact with mycotoxins present in food, is particularly vulnerable to the harmful effects of these toxins. One of the lesser-known aspects of the impact of mycotoxins on the gastrointestinal tract is the influence of these substances on gastrointestinal innervation. Therefore, the present study is the first review of current knowledge concerning the influence of mycotoxins on the enteric nervous system, which plays an important role, not only in almost all regulatory processes within the gastrointestinal tract, but also in adaptive and protective reactions in response to pathological and toxic factors in food.

show abstract

“…Oxidative stress participates in the initiation and development of cardiovascular and digestive diseases and is considered as the underlying mechanism of intestinal barrier dysfunction [24]. The underlying mechanism of T-2 toxin-triggered cell apoptosis and tissue damage was shown to be oxidative stress, which was partially regulated by the overproduction of ROS, inhibition of the activity of antioxidant enzymes and an increase in lipid peroxidation [25]. These findings are similar to the results of the present study showing that T-2 toxin remarkably declined the levels of CAT, GSH and GSH-PX and elevated the accumulation of MDA in the intestine.…”

Section: Discussionmentioning

confidence: 99%

Betulinic Acid Ameliorates the T-2 Toxin-Triggered Intestinal Impairment in Mice by Inhibiting Inflammation and Mucosal Barrier Dysfunction through the NF-κB Signaling Pathway

Luo

Huang

Zhu

et al. 2020

Toxins

View full text Add to dashboard Cite

T-2 toxin, a trichothecene mycotoxin produced by Fusarium, is widely distributed in crops and animal feed and frequently induces intestinal damage. Betulinic acid (BA), a plant-derived pentacyclic lupane-type triterpene, possesses potential immunomodulatory, antioxidant and anti-inflammatory biological properties. The current study aimed to explore the protective effect and molecular mechanisms of BA on intestinal mucosal impairment provoked by acute exposure to T-2 toxin. Mice were intragastrically administered BA (0.25, 0.5, or 1 mg/kg) daily for 2 weeks and then injected intraperitoneally with T-2 toxin (4 mg/kg) once to induce an intestinal impairment. BA pretreatment inhibited the loss of antioxidant capacity in the intestine of T-2 toxin-treated mice by elevating the levels of CAT, GSH-PX and GSH and reducing the accumulation of MDA. In addition, BA pretreatment alleviated the T-2 toxin-triggered intestinal immune barrier dysregulation by increasing the SIgA level in the intestine at dosages of 0.5 and 1 mg/kg, increasing IgG and IgM levels in serum at dosages of 0.5 and 1 mg/kg and restoring the intestinal C3 and C4 levels at a dosage of 1 mg/kg. BA administration at a dosage of 1 mg/kg also improved the intestinal chemical barrier by decreasing the serum level of DAO. Moreover, BA pretreatment improved the intestinal physical barrier via boosting the expression of ZO-1 and Occludin mRNAs and restoring the morphology of intestinal villi that was altered by T-2 toxin. Furthermore, treatment with 1 mg/kg BA downregulated the expression of p-NF-κB and p-IκB-α proteins in the intestine, while all doses of BA suppressed the pro-inflammatory cytokines expression of IL-1β, IL-6 and TNF-α mRNAs and increased the anti-inflammatory cytokine expression of IL-10 mRNA in the intestine of T-2 toxin-exposed mice. BA was proposed to exert a protective effect on intestinal mucosal disruption in T-2 toxin-stimulated mice by enhancing the intestinal antioxidant capacity, inhibiting the secretion of inflammatory cytokines and repairing intestinal mucosal barrier functions, which may be associated with BA-mediated inhibition of the NF-κB signaling pathway activation.

show abstract

T-2 toxin neurotoxicity: role of oxidative stress and mitochondrial dysfunction

Cited by 114 publications

References 135 publications

Molecular Mechanisms Underlying Protective Role of Quercetin on Copper Sulfate-Induced Nephrotoxicity in Mice

Molecular Mechanisms Underlying Protective Role of Quercetin on Copper Sulfate-Induced Nephrotoxicity in Mice

Mycotoxins and the Enteric Nervous System

Betulinic Acid Ameliorates the T-2 Toxin-Triggered Intestinal Impairment in Mice by Inhibiting Inflammation and Mucosal Barrier Dysfunction through the NF-κB Signaling Pathway

Contact Info

Product

Resources

About