Lycopene regulates the mitochondrial unfolded protein response to prevent DEHP-induced cardiac mitochondrial damage in mice

Lycopene (LYC), as a kind of carotene, has antioxidant effects. Di(2-ethylhexyl) phthalate (DEHP) was used to improve the flexibility of plastics. However, the potential role of LYC in DEHP induced cardiac injury in mice remains unclear. Therefore, the aim of this study was to investigate the role and mechanism of LYC in DEHP induced cardiac injury. Male ICR mice were treated with DEHP (500 or 1000 mg per kg BW per day) and/or LYC (5 mg per kg BW per day) for 28 days. The results of histopathology and ultrastructure showed that LYC relieved the decrease of mitochondrial volume density and myocardial fibre disorder induced by DEHP. Subsequently, LYC attenuated DEHP-induced mitochondrial damage, mitochondrial unfolded protein response (UPRmt) activation, nuclear factor erythroid 2-related factor 2 (Nrf2) mediated oxidative stress and heat shock response (HSR) activation induced by DEHP. LYC regulates UPRmt to prevent DEHP-induced cardiac mitochondrial damage. Thus, this study provided new evidence of UPRmt as a target for LYC treatment preventing DEHP-induced cardiac disease.