Journal
CHEMOSPHERE
Volume 330, Issue -, Pages -Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.chemosphere.2023.138714
Keywords
Dichlorvos; ER stress; Necroptosis; Autophagy; SIRT1
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In this study, we investigated the mechanism of Dichlorvos-induced toxicity in cardiac cells. Cell death by necroptosis was induced after 24-hour exposure to Dichlorvos, while autophagy was enhanced following 6-hour exposure. Autophagy acts as a protective mechanism against the toxicity induced by this pesticide. The inhibition of deacetylase sirtuin 1 (SIRT1) increased necroptosis, while its activation decreased cell death.
In this study we aimed to understand the underlying mechanism of Dichlorvos-induced toxicity in cardiac cells. For this end, cells were treated by 170 mu M of Dichlorvos (DDVP) (corresponding to the IC50) and molecular events were monitored by flow cytometry and western blotting. We have first demonstrated that cell exposure to DDVP for 24 h induced cell death by necroptosis. In fact, cell treatment with DDVP upregulated RIP1 expression and we have shown that chemical inhibition of RIP1 kinase activity by necrostatin-1 (Nec-1) greatly prevented from the induced cell death. Besides, we have demonstrated that, while there was no observed cell death following short exposure to DDVP (6 h), autophagy was enhanced, as proven by the increase in the level of both Beclin-1 and LC3-II and the accumulation of the CytoID (R) autophagy detection probe. Besides, when autophagy was inhibited by chloroquine (CQ) the percentage of necroptosis was significantly increased, suggesting that autophagy acts to protect cardiac cells against the toxicity induced by this pesticide. Concurrently, we have shown that the inhibition of the deacetylase sirtuin 1 (SIRT1) by EX527 or its knockdown by siRNA significantly increased DDVP-induced necroptosis, whereas when SIRT1 was activated by resveratrol (RSV) a significant decrease in DDVP-induced cell death was observed. In addition, we revealed that when the autophagy was
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