Tebuconazole and Econazole Act Synergistically in Mediating Mitochondrial Stress, Energy Imbalance, and Sequential Activation of Autophagy and Apoptosis in Mouse Sertoli TM4 Cells: Possible Role of AMPK/ULK1 Axis

• DOI: 10.1093/toxsci/kfz031
• Publication Date: 2019-01-23T20:42:52Z
• Authors: Sabrina Petricca; Vincenzo Flati; Giuseppe Celenza; Jacopo Di Gregorio; Anna Rita Lizzi; Carla Luzi; Loredana Cristiano; Benedetta Cinque; Gianna Rossi; Claudio Festuccia; Roberto Iorio
• Keywords: Tebuconazole; Econazole; Energy charge

Tebuconazole and Econazole are triazole imidazole fungicides currently used worldwide. Although their reproductive toxicity in mammals has been described, effect on male systems poorly investigated. As humans may be exposed to different azole compounds simultaneously, the combinational vitro of (MIX) mouse Sertoli TM4 cells was This study demonstrates that (40 µM) (20 act synergistically mediating decrease mitochondrial membrane potential (ΔΨm) changes morphology. These events were associated with ATP depletion, cell cycle arrest, sequential activation autophagy apoptosis. Remarkable differences other parameters such as AMP/ATP ratio adenylate energy charge observed. Pharmacological inhibition by bafilomycin A1 leads enhanced MIX-induced apoptosis suggesting an adaptive cytoprotective function for MIX-modulated autophagy. Finally, a possible role AMPK/ULK1 axis signalling cascades response stress hypothesized. Consistently, ULK1 Ser 555 phosphorylation occurred AMPK (Thr 172) activation. In conclusion, combination, at concentrations relevant dermal clinical exposure, induces severe SCs. Consequently, prolonged exposure affect ability re-establish homeostasis trigger