Brain injury, genotoxic damage and oxidative stress induced by Bromuconazole in male Wistar rats and in SH-SY5Y cell line

Abstract

Background Bromuconazole is a widely used triazole against various fungi disease. It’s employment provokes harmful effects on the environment and human health. In the present study, we explored bromuconazole toxic effects in both rat brain tissue and SH-SY5Y cell line. Methods Male Wistar rats were administrated orally with Bromuconazole (NOEL/4, NOEL o and NOEL ×2) daily for consecutive 28 days. In addition, neuronal SH-SY5Y cell line was used. The rat brains and SH-SY5Y cells were collected and analysed for AChE activity, oxidative stress biomarkers, genotoxicity and histopathological alterations. Results Our results showed that rat exposure to bromuconazole at doses corresponding to NOEL/4, NOEL and NOEL ×2 caused brain histopathological alteration and decrease in acetylcholine esterase (AChE) activity. In SH-SY5Y cell line, bromuconazole strongly induced cell mortality with an IC50 about 250 µM. Bromuconazole induced also DNA damage as assessed by comet assay in both rat brain tissue and SH-SY5Y cell. Moreover, bromuconazole increased ROS production, malondialdehyde (MDA) and protein carbonyl (PC) levels and enhanced the enzymatic activities of catalase (CAT), superoxide dismutase (SOD), Glutathione-S-transferase (GST) and peroxidase (GPx) in the two studied systems. Conclusion Therefore, we can deduce that bromuconazole-caused neurotoxicity may be related to oxidative statue disturbance. HIGHLIGHTS Bromuconzole causes oxidative stress in the brain tissue of male Wistar rats. Bromuconazole enhances MDA, PC levels and induces DNA damage in rat brain. Bromuconazole provokes disturbance of the neuronal antioxidant system. Bromuconazole induces histopathological alterations in rat brain. Bromuconazole exposure induced cytotoxic effects and DNA damage in SH-SY5Y cells. Bromuconazole exposure induced oxidative stress in SH-SY5Ycells.