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Oxidative stress, apoptosis and histopathological alterations in brain stem and diencephalon induced by subacute exposure to fipronil in albino rats

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Abstract

Fipronil (FIP) is a highly effective insecticide that has been used in agriculture and veterinary medicine. Its neurotoxic effect to insects and to non-target organisms, after nonintentional exposure, was reported. Many studies were conducted to evaluate FIP effects on mammals. However, slight is known about its effect on the brain stem and diencephalon. The current study was designed to investigate the ability of FIP to induce oxidative stress as a molecular mechanism of FIP neurotoxicity that resulted in apoptosis and neural tissue reactivity in these regions. Ten adult male rats received 10 mg/kg of FIP technical grade by oral gavage, daily for 45 days. Brain stem and diencephalon were processed to examine oxidative stress–induced macromolecular alteration (MDA, PCC and DNA fragmentation). Also, the histopathological assessment and immunoreactivity for caspase-3 (active form), iNOS and GFAP were performed on the thalamus, hypothalamus and medulla oblongata. Our results revealed that FIP significantly raised MDA, PCC and DNA fragmentation (p ≤ 0.05). In addition, significantly increased immunoreactivity to GFAP, iNOS and caspase-3 (active form) in the FIP-treated group was noticed (p ≤ 0.05). Moreover, alterations in the histoarchitecture of the neural tissue of these regions were observed. We conclude that FIP can induce oxidative stress, leading to apoptosis and tissue reaction in brain stem and diencephalon.

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Acknowledgements

This project was supported via general scientific research department of Cairo University, Egypt.

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Contributions

Moukhtar H.G. Moussa and Gehad Abd El-Fattah Hassan Elbargeesy conceived the idea of the research and managed the study. Huda O. AbuBakr was responsible for performing the biochemical analysis of the study in addition to her contribution in writing the manuscript sections related to the biochemical analysis. Zainab Sabry Othman Ahmed contributed by samples collection, writing the manuscript, and revising it critically in addition to submission of the manuscript as she is the corresponding author. Mohamed A. Awad contributed by managing the experiment, collection of samples, performing the histological analysis and writing the manuscript.

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Correspondence to Zainab Sabry Othman Ahmed.

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The study was conducted in Faculty of Veterinary Medicine, Cairo University, Giza, Egypt. The maintenance of experimental rats and experimental procedures implemented were accepted by Institutional Animal Care and Use committee (IACUC). (Reference No. Vet CU20022020135).

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The authors declare no competing interests.

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Highlights:

• FIP induces histopathological alterations in diencephalon and brain stem.

• FIP increases GFAP, iNOS and caspase-3 immunoexpression in thalamus, medulla oblongata and hypothalamus.

• FIP elevates MDA, PCC and DNA fragmentation in diencephalon and brain stem.

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Awad, .A., Ahmed, Z.S.O., AbuBakr, H.O. et al. Oxidative stress, apoptosis and histopathological alterations in brain stem and diencephalon induced by subacute exposure to fipronil in albino rats. Environ Sci Pollut Res 29, 936–948 (2022). https://doi.org/10.1007/s11356-021-15537-3

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  • DOI: https://doi.org/10.1007/s11356-021-15537-3

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