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Detoxification gene expression, genotoxicity, and hepatorenal damage induced by subacute exposure to the new pyrethroid, imiprothrin, in rats

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Abstract

The pyrethroid imiprothrin is widely used worldwide for control of insects in the agriculture and public health sectors. No sufficient information is however available concerning detoxification gene expression, i.e., cytochrome P450 1A2 (CYP1A2) and metallothionein 1a gene, oxidative stress, lipid peroxidation, DNA damage, cytotoxicity, genotoxicity, and organ injury induced by imiprothrin in mammals. This study is designed to explain the mechanism of imiprothrin induced detoxification gene expression, DNA damage, cytotoxicity, genotoxicity, and organ toxicity in male rats. The benchmark dose (BMD) was calculated to find the best sensitive markers to imiprothrin toxicity. Imiprothrin was injected intraperitoneally (i.p.) into male rats once a day for 5 days with doses of 19, 38, and 75 mg/kg body weight (b.wt.). Imiprothrin caused a significant increase in lipid peroxidation and changes in oxidative stress biomarkers in treated rats. Significant dose-dependent changes in the liver and kidney biomarkers were observed. Histopathological alterations were seen in the liver and kidney tissue of male rats. Imiprothrin also significantly increased chromosomal aberrations (CA) and micronuclei in bone-marrow cells, and induced lipid peroxidation, oxidative stress, cytotoxicity, and liver and kidney dysfunction, and damage. Imiprothrin induced DNA damage and over detoxification gene expression of CYP1A2 and metallothionein 1a gene in hepatocytes of male rats. Imiprothrin thus shows clastogenic and genotoxic potential. The mechanism for hepatorenal toxicity and injury, genotoxicity/cytotoxicity of imiprothrin might be due to enhanced lipid peroxidation, and oxidative stress associated with overproduction of free radicals, especially reactive oxygen species, and an imbalance in redox status. From the BMD models, aspartate aminotransferase (AST), total protein, uric acid, superoxide dismutase (SOD), and micronuclei (MPEs) were very sensitive markers to imiprothrin toxicity.

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Data availability

The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.

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Acknowledgements

The authors are thankful to the NRC to support this work and Prof. Dr. Wagdy Khalil, department of cell biology, NRC for helping in cytochrome P450 1A2 (CYP1A2) and metallothionein 1a gene expression and comet assay.

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All authors were involved in the design of the study and collection and analysis of data. EH and AM performed the genotoxic analysis and interpretation. NE performed the histopathology study and interpretation. SM and AM performed the biochemical and BMD analysis and interpretation all the data obtained from this study and was a major contributor in writing the manuscript. All authors read and approved the final manuscript

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Correspondence to Abdel-Tawab H. Mossa.

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All experiments were completed under the standard conditions in the Animal Breeding House (ABH), of the National Research Centre (NRC), Dokki, Cairo, Egypt. The Local Ethics Committee at the National Research Centre (NRC) approved the ABH (without number).

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Mohafrash, S.M.M., Hassan, E.E., El-shaer, N.H. et al. Detoxification gene expression, genotoxicity, and hepatorenal damage induced by subacute exposure to the new pyrethroid, imiprothrin, in rats. Environ Sci Pollut Res 28, 33505–33521 (2021). https://doi.org/10.1007/s11356-021-13044-z

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