T-2 Toxin-Induced Hepatotoxicity in HepG2 Cells Involves the Inflammatory and Nrf2/HO-1 Pathways

Area of Science:

• Toxicology
• Cell Biology
• Molecular Biology

Background:

• T-2 toxin is a highly toxic mycotoxin commonly found in cereals and cereal-based foods.
• Dietary exposure to T-2 toxin poses a risk to the general population.
• Understanding T-2 toxin's cellular mechanisms is crucial for assessing its health impacts.

Purpose of the Study:

• To investigate the effects of T-2 toxin on HepG2 cells, focusing on morphological changes, oxidative stress, and inflammatory responses.
• To analyze the expression of key inflammatory cytokines (IL-1β, IL-6, TNF-α) and proteins involved in oxidative stress (Nrf2, HO-1) upon T-2 toxin exposure.

Main Methods:

• HepG2 cells were exposed to varying concentrations of T-2 toxin (7.5, 15, and 30 nM).
• Morphological changes were assessed using indirect immunofluorescence.
• mRNA and protein expression levels were quantified using qPCR and Western blot assays.

Main Results:

• T-2 toxin exposure induced concentration-dependent morphological alterations in HepG2 cells, shifting from circular to elongated shapes.
• Upregulation of inflammatory cytokine mRNA (IL-1β, IL-6, TNF-α) was observed, with TNF-α showing the most significant increase at 30 nM T-2.
• The Nrf2/HO-1 oxidative stress pathway was modulated, with HO-1 upregulated at low T-2 concentrations and Nrf2 downregulated across all tested concentrations.

Conclusions:

• T-2 toxin exposure leads to significant inflammatory responses and morphological changes in HepG2 cells.
• The study confirms T-2 toxin's hepatotoxicity involves modulation of the Nrf2/HO-1 pathway.
• Future research should explore the potential cytoprotective effects of natural antioxidants against T-2 toxin-induced damage.