The Fungicide Ipconazole Can Activate Mediators of Cellular Damage in Rat Brain Regions.

This study aimed to investigate the toxicity of the fungicide ipconazole on oxidative status, cell death and inflammasome complex activation in the hypothalamus, cerebral cortex, striatum and hippocampus of rats. Female albino rats were randomly divided into a control group and four groups treated with ipconazole at doses of 1, 5, 10 and 20 mg/kg b.w., administered for six days. Ipconazole significantly increased MDA and ROS levels in all brain regions studied, while reducing catalase enzyme activity. The molecular expression of cell death-related genes (AKT1, APAF1, BNIP3, CASP3 and BAX) and the inflammasome complex (CASP1, IL1ß, IL6, NLRP3, NFĸB and TNFα) was also assessed, showing increased expression in at least one brain region. The findings demonstrate that ipconazole induces central nervous system toxicity in mammals, highlighting its potential role as a risk factor in the development of neurodegenerative disorders in individuals exposed to this contaminant.

Potential Involvement of Oxidative Stress, Apoptosis and Proinflammation in Ipconazole-Induced Cytotoxicity in Human Endothelial-like Cells.

Triazole fungicides are widely used in the world, mainly in agriculture, but their abuse and possible toxic effects are being reported in some in vivo and in vitro studies that have demonstrated their danger to human health. This in vitro study evaluated the cytotoxicity, oxidative stress and proinflammation of EA.hy926 endothelial cells in response to ipconazole exposure. Using the MTT assay, ipconazole was found to produce a dose-dependent reduction (*** p < 0.001; concentrations of 20, 50 and 100 µM) of cell viability in EA.hy926 with an IC50 of 29 µM. Also, ipconazole induced a significant increase in ROS generation (** p < 0.01), caspase 3/7 (** p < 0.01), cell death (BAX, APAF1, BNIP3, CASP3 and AKT1) and proinflammatory (NLRP3, CASP1, IL1ß, NFκB, IL6 and TNFα) biomarkers, as well as a reduction in antioxidant (NRF2 and GPx) biomarkers. These results demonstrated that oxidative stress, proinflammatory activity and cell death could be responsible for the cytotoxic effect produced by the fungicide ipconazole, such that this triazole compound should be considered as a possible risk factor in the development of alterations in cellular homeostasis.

Ipconazole Induces Oxidative Stress, Cell Death, and Proinflammation in SH-SY5Y Cells.

Ipconazole is an antifungal agrochemical widely used in agriculture against seed diseases of rice, vegetables, and other crops; due to its easy accumulation in the environment, it poses a hazard to human, animal, and environmental health. Therefore, we investigated the cytotoxic effect of ipconazole on SH-SY5Y neuroblastoma cells using cell viability tests (MTT), ROS production, caspase3/7 activity, and molecular assays of the biomarkers of cell death (Bax, Casp3, APAF1, BNIP3, and Bcl2); inflammasome (NLRP3, Casp1, and IL1ß); inflammation (NFκB, TNFα, and IL6); and antioxidants (NRF2, SOD, and GPx). SH-SY5Y cells were exposed to ipconazole (1, 5, 10, 20, 50, and 100 µM) for 24 h. The ipconazole, in a dose-dependent manner, reduced cell viability and produced an IC50 of 32.3 µM; it also produced an increase in ROS production and caspase3/7 enzyme activity in SH-SY5Y cells. In addition, ipconazole at 50 µM induced an overexpression of Bax, Casp3, APAF1, and BNIP3 (cell death genes); NLRP3, Casp1, and IL1B (inflammasome complex genes); and NFκB, TNFα, and IL6 (inflammation genes); it also reduced the expression of NRF2, SOD, and GPx (antioxidant genes). Our results show that ipconazole produces cytotoxic effects by reducing cell viability, generating oxidative stress, and inducing cell death in SH-SY5Y cells, so ipconazole exposure should be considered as a factor in the presentation of neurotoxicity or neurodegeneration.