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

Xiya Zhang, Ying Wang, Tony Velkov, Shusheng Tang, Chongshan Dai

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47 Citations (Scopus)


The molecular mechanisms of T-2 mycotoxin induced neurotoxicity remains enigmatic. In the present study we show that T-2 toxin induced neurotoxicity in mouse neuroblastoma2a (N2a) cells is both dose- and time-dependent and is associated with oxidative stress, mitochondrial dysfunction and apoptosis. T-2 toxin treatment of N2a cells at 10, 20, 40 and 80 ng/mL for 24 h significantly up-regulated the mRNA expression of p53, Bax, and caspase-8 and down-regulated the expression of Nrf2 and HO-1 mRNA and protein expression. Activation of caspases-8, -9 and -3 was also evident in a concentration-dependent manner. Pre-treatment of the cells with the antioxidant N-acetyl-cysteine markedly suppressed T-2 toxin-induced neurotoxicity and caspase activation. Conversely, pre-treatment of the cells with the Nrf2 inhibitor brusatol or the HO-1 inhibitor zinc protoporphyrin IX, enhanced T-2 toxin induced neurotoxicity and increased the activation of caspase-9 and -3. Taken together, these novel findings suggest that T-2 toxin-induced neurotoxicity in N2a cells involves oxidative stress, mitochondrial dysfunction and apoptosis via the inhibition of the Nrf2/HO-1 and activation of p53 pathway. The present study highlights the potential of developing much needed pharmacological interventions to prevent T-2 toxin neurotoxicity.

Original languageEnglish
Pages (from-to)88-97
Number of pages10
JournalFood and Chemical Toxicology
Publication statusPublished - Apr 2018
Externally publishedYes


  • Apoptosis
  • Neurotoxicity
  • Nrf2/HO-1 signaling pathway
  • ROS
  • T-2 toxin

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