Synergistic Activity of Ketoconazole and Miconazole with Prochloraz in Inducing Oxidative Stress, GSH Depletion, Mitochondrial Dysfunction, and Apoptosis in Mouse Sertoli TM4 Cells
| Autor: | Sabrina Petricca, Giuseppe Celenza, Carla Luzi, Benedetta Cinque, Anna Rita Lizzi, Nicola Franceschini, Claudio Festuccia, Roberto Iorio |
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| Jazyk: | angličtina |
| Rok vydání: | 2022 |
| Předmět: |
Male
Miconazole enzymatic activity Apoptosis mitochondrial activity Catalysis Inorganic Chemistry mouse Sertoli TM4 cells Mice fluconazole Animals Physical and Theoretical Chemistry SOD ROS generation and apoptosis Molecular Biology GSH homeostasis Spectroscopy prochloraz Mammals Organic Chemistry Imidazoles General Medicine miconazole and ketoconazole synergistic effects oxidative stress Glutathione Computer Science Applications Mitochondria Oxidative Stress Reactive Oxygen Species Ketoconazole |
| Zdroj: | International Journal of Molecular Sciences; Volume 23; Issue 10; Pages: 5429 |
| Popis: | Triazole and imidazole fungicides represent an emerging class of pollutants with endocrine-disrupting properties. Concerning mammalian reproduction, a possible causative role of antifungal compounds in inducing toxicity has been reported, although currently, there is little evidence about potential cooperative toxic effects. Toxicant-induced oxidative stress (OS) may be an important mechanism potentially involved in male reproductive dysfunction. Thus, to clarify the molecular mechanism underlying the effects of azoles on male reproduction, the individual and combined potential of fluconazole (FCZ), prochloraz (PCZ), miconazole (MCZ), and ketoconazole (KCZ) in triggering in vitro toxicity, redox status alterations, and OS in mouse TM4 Sertoli cells (SCs) was investigated. In the present study, we demonstrate that KCZ and MCZ, alone or in synergistic combination with PCZ, strongly impair SC functions, and this event is, at least in part, ascribed to OS. In particular, azoles-induced cytotoxicity is associated with growth inhibitory effects, G0/G1 cell cycle arrest, mitochondrial dysfunction, reactive oxygen species (ROS) generation, imbalance of the superoxide dismutase (SOD) specific activity, glutathione (GSH) depletion, and apoptosis. N-acetylcysteine (NAC) inhibits ROS accumulation and rescues SCs from azole-induced apoptosis. PCZ alone exhibits only cytostatic and pro-oxidant properties, while FCZ, either individually or in combination, shows no cytotoxic effects up to 320 µM. |
| Databáze: | OpenAIRE |
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