DRUG AND CHEMICAL TOXICOLOGY, cilt.46, sa.5, ss.944-954, 2023 (SCI-Expanded)
Citrinin (CIT) is a mycotoxin produced as a secondary product by the genera Aspergillus, Penicillium, Monascus, and other strains. CIT has the potential for contaminating animal feed and human food such as maize, wheat, rye, barley, oats, rice, cheese, and sake. Although CIT is primarily known as a nephrotoxic mycotoxin, it also affects other organs, including the liver and bone marrow, and its mechanisms of toxicity have not been clearly elucidated. There is a further lack of studies investigating the potential for CIT-induced neurotoxicity and its mechanisms. In the current study, SH-SY5Y human neuroblastoma cell line was treated with CIT for 24 h to evaluate various toxicological endpoints, such as reactive oxygen species (ROS) production and apoptosis induction. Results indicate that CIT has an IC50 value of 250.90 mu M and cell proliferation decreased significantly at 50 and 100 mu M CIT concentrations. These same concentrations also caused elevated ROS production (>= 34.76%), apoptosis (>= 9.43-fold) and calcium ion mobilization (>= 36.52%) in the cells. Results show a significant decrease in the mitochondrial membrane potential (>= 86.8%). We also found that CIT significantly upregulated the expression of some genes related to oxidative stress and apoptosis, while downregulating others. These results suggest that apoptosis and oxidative stress may be involved in the mechanisms underlying CIT-induced neurotoxicity.