Role of pyrethroid derivatives in autophagy and apoptosis crosstalk signaling and potential risk for malignancies
Effect of pyrethroid derivatives on the induction of autophagy. Credit: 2022 Puvula et al.
Pyrethroids are widely used insecticides due to their potential insecticidal activity in Asia, especially India and in different countries worldwide to combat mosquitoes and insects for household needs. or agriculture. The continued rampant and uncontrolled use of pyrethroids and its derivatives has resulted in multiple adverse effects leading to potential risk factors for damage to organ systems.
Allethrin and prallethrin are widely used, however their effects on human primary cells have been limited or have not been fully reported. Potential mechanisms by which allethrin and prallethrin regulate human primary cells, particularly molecular mechanism or the connectivity of autophagy-apoptosis and their clinical relevance in humans or patients is not well defined.
In a new research paper published on online target on December 17, 2022, researchers Jyothi Puvula, Narendra Maddu, Nagajothi Gutam, Asha Parimal and Raghavendra B. Pongali from Sri Krishnadevaraya University, Queen Mary University, University of Manipal and Biomedical Genomics Research Institute nationals provided evidence that both allethrin and prallethrin in user samples induce significant Ccl2 mRNA expression, increased reactive oxygen mediators, inhibition of membrane-bound enzymes, and altered membrane fluidity. .
The administration of pyrethroid derivatives induced levels of lipid peroxidation and induced binding activities of transcription factors (tfs) such as CEBP-β and NF-AT. Pyrethroid derivatives induce autophagy, stimulate intracellular Ca2+ levels, calcineurin and the upregulated proapoptotic genes, DAPK1, Bim.
“Our current study probably includes the initial investigation of a very new mechanism of programmed pyrethroid derivatives. dead cells in different subsets or cell types, such as human primary cells, where this is a late event, has been recorded,” the researchers said.
Therefore, the present study may have implications in various pyrethroid derivatives-associated hematological cancers and immunosuppressive or autoimmune disorders. In the most important case, the researchers presented the data saying that pyrethroids derivatives that induce multiple cellular signaling cascades, such as CEBP-β, NF-AT, ERK and MAPK have a role in autophagy; effective synergistic effect on programmed death, thereby causing hematologic tumors and toxicity or immune related disorders.
Overall, this present study may facilitate the formulation of therapeutic or interventional targets that may reduce the effects or effects of pyrethroid derivatives by targeting the signaling cascade serves to minimize the modulation of autophagy-mediated apoptosis,” the researchers concluded.
Jyothi Puvula et al., Role of pyrethroid derivatives in autophagy and programmed death crosstalk signaling and potential risk for malignancies, online target (2022). DOI: 10.18632/oncotarget.28328
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