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.

Keywords:

• Bromuconazole
• rat brain damage
• SH-SY5Y cells
• oxidative stress
• genotoxic effect

Ethical approval

The experimental strategy was done as accorded by ARRIVES Guidelines for Animal Care and in agreement with the local Ethics Committee of Faculty of Pharmacy of Monastir.

Authors contributions

Dr. Karima Rjiba Touati designed the study, conducted the study and wrote the manuscript. Dr. Hiba Hamdi supervised the study and conducted statistical analysis, Mis. Asma M’nassri and Mis. Siwar Rich conducted statistical analysis. Moncef Mokni participated in the biochemical and histological studies. The authors are thankful to Pr. Salwa Abid for their laboratory supports.

Informed consent

The author(s) grant the publisher an exclusive licence to publish the article.

Disclosure statement

The authors declare the absence of conflicts of interest concerning the research, the authorship as well as the publication of this article.

Data availability statement

The datasets used and analysed in this research are available from the corresponding author upon reasonable request.

Additional information

Funding

Our research was designed in accordance with ethical standards and supported by the Ministry of Higher Education and Scientific Research.