T-2 toxin-induced toxicity in neuroblastoma-2a cells involves the generation of reactive oxygen, mitochondrial dysfunction and inhibition of Nrf2/HO-1 pathway

Area of Science:

• Neuroscience
• Toxicology
• Cell Biology

Background:

• T-2 mycotoxin is a potent neurotoxic agent.
• The precise molecular pathways of T-2 toxin neurotoxicity are not fully understood.

Purpose of the Study:

• To elucidate the molecular mechanisms underlying T-2 toxin-induced neurotoxicity in mouse neuroblastoma 2a (N2a) cells.
• To investigate the roles of oxidative stress, mitochondrial dysfunction, and apoptosis in T-2 toxin neurotoxicity.

Main Methods:

• N2a cells were treated with varying concentrations of T-2 toxin.
• mRNA and protein expression of key genes (p53, Bax, caspase-8, Nrf2, HO-1) were analyzed.
• Caspase activation was assessed.
• The effects of N-acetyl-cysteine, brusatol, and zinc protoporphyrin IX were evaluated.

Main Results:

• T-2 toxin induced dose- and time-dependent neurotoxicity, oxidative stress, mitochondrial dysfunction, and apoptosis.
• T-2 toxin altered the expression of p53, Bax, caspase-8, Nrf2, and HO-1, and activated caspases.
• N-acetyl-cysteine mitigated T-2 toxin-induced neurotoxicity and caspase activation.
• Inhibition of Nrf2/HO-1 exacerbated T-2 toxin neurotoxicity.

Conclusions:

• T-2 toxin neurotoxicity involves oxidative stress, mitochondrial dysfunction, and apoptosis.
• The Nrf2/HO-1 pathway is inhibited, while the p53 pathway is activated.
• These findings suggest potential therapeutic targets for T-2 toxin neurotoxicity.