DEHP-induced mitophagy and mitochondrial damage in the heart are associated with dysregulated mitochondrial biogenesis.

Di(2-ethylhexyl) phthalate (DEHP) is a plasticizer widely used in agricultural and industrial plastic products. Many researchers have demonstrated that DEHP can cause varying degrees of harm to the heart. This research investigated the mechanism by which DEHP causes heart damage in quail. The quail were treated with DEHP (250 mg/kg BW/day, 500 mg/kg BW/day or 750 mg/kg BW/day) for 45 days. The present study suggested that DEHP could cause varying levels of heart damage, including disordered myocardial fiber arrangements, myocardial fiber breakage and myocardial cell swelling. The results showed that DEHP induced mitochondrial damage, such as cavitation lesions and mitochondrial crest breakage. DEHP damaged mitochondria and inhibited nuclear respiratory factor 1 (Nrf1)-mediated mitochondrial biogenesis, which led to mitochondrial damage. DEHP caused oxidative stress in the heart and activated the defense mechanism of the nuclear factor red blood cell 2 related factor 2 (Nrf2) system. DEHP-induced mitophagy was related to a decline in mitochondrial biogenesis and disordered mitochondrial dynamics. The data indicated that DEHP exposure damaged cardiac mitochondria and caused mitophagy and cardiotoxicity. Of note, this study showed that DEHP-induced mitophagy and mitochondrial damage are associated with the dysregulation of mitochondrial biogenesis. This study showed that DEHP exposure can cause cardiotoxicity, which was closely related to mitochondrial damage. DEHP inhibited Nrf1-mediated mitochondrial biogenesis and caused an imbalance in mitochondrial dynamics. DEHP exposure increased the level of Nrf2 because it induced oxidative stress and activated the Nrf2 signaling pathway. DEHP-induced mitochondrial damage leads to the occurrence of mitophagy, which ultimately leads to cardiotoxicity. This study provided new evidence for the effect of DEHP on the cardiotoxicity of quail. [Display omitted] • DEHP caused an Nrf1-mediated decline in mitochondrial biogenesis. • DEHP-induced cardiac oxidative stress damage activates the Nrf2 signaling pathway. • DEHP caused disordered mitochondrial dynamics in the heart of quail. • DEHP-induced mitophagy was associated with reduced mitochondrial biogenesis. [ABSTRACT FROM AUTHOR]