Subchronic exposure to fenpyroximate causes multiorgan toxicity in Wistar rats by disrupting lipid profile, inducing oxidative stress and DNA damage

Abstract

Background

Fenpyroximate (FEN) is an acaricide that inhibits the complex I of the mitochondrial respiratory chain in mites. Data concerning mammalian toxicity of this acaricide are limited; thus the aim of this work was to explore FEN toxicity on Wistar rats, particularly on cardiac, pulmonary, and splenic tissues and in bone marrow cells.

Methods

rats were treated orally with FEN at 1, 2, 4, and 8 mg/Kg bw for 28 days. After treatment, we analyzed lipid profile, oxidative stress and DNA damage in rat tissues.

Results

FEN exposure increased creatinine phosphokinase (CPK) and lactate dehydrogenase (LDH) activities, elevated total cholesterol (T-CHOL), triglycerides (TG), and low-density lipoprotein cholesterol (LDL-C) concentrations, while decreasing high-density lipoprotein cholesterol (HDL-C). It inhibited acetylcholinesterase (AChE) activity, enhanced lipid peroxidation, protein oxidation, and modulated antioxidant enzymes activities (superoxide dismutase, catalase, glutathione peroxidase, and glutathione S-transferase). Comet assay indicated that FEN induced a dose-dependent DNA damage, contrasting with the micronucleus test showing no micronuclei formation. Nonetheless, FEN exhibited cytotoxicity to bone marrow cells, as evidenced by a reduction in the number of immature erythrocytes among total cells.

Conclusion

FEN appears to carry out its genotoxic and cytotoxic activities most likely through an indirect pathway that involves oxidative stress.

Keywords:

• Fenpyroximate
• biochemical markers
• AChE activity
• oxidative stress
• genotoxicity
• heart
• lungs
• spleen
• bone marrow cells
• Wistar rats

Authors’ contributions

This research was designed, conducted, and written by Dr. I. Ayed-Boussema; the study was supervised by Miss A. M’nassri; Dr. H. Hamdi conducted the statistical analysis, and Pr. S. Abid provided access to laboratory support.

Consent for publication

The authors grant the publisher an exclusive license to publish the article.

Disclosure statement

The authors declare no competing interests.

Ethics approval and consent to participate

The experimental strategy was done with ethical standards accorded by ARRIVE Guidelines for Animal Care and Use of Laboratory animals, and the study was approved by the University of Tunisia Ethical Committee (approval number: FST/LNFP/Pro 152012).

Data availability statement

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

Additional information

Funding

Our research was supported by the ‘Tunisian Ministry of Higher Education and Scientific Research’