Abstract
Lycopene (LYC) is a carotenoid, has antioxidant properties. This study investigated whether lycopene attenuates aristolochic acids (AAs) -induced chronic kidney disease. In this experiment, lycopene was used to intervene C57BL/6 mice with renal injury induced by aristolochic acid exposure. The histomorphological changes and serological parameters of the kidney were measured in order to assess the alleviating effect of lycopene on renal injury in aristolochic acid nephropathy. In vitro and in vivo experiments were carried out to verify the main mechanism of action and drug targets of lycopene in improving aristolochic acid nephropathy (AAN) and by various experimental methods such as ELISA, immunohistochemistry, immunofluorescence, Western-blot and qRT-PCR. The results showed that oxidative stress injury was induced in the kidney of mice after AAI exposure, resulting in inflammatory response and tubular epithelial cell apoptosis. The results showed that the Nrf2/HO-1 antioxidant signaling pathway was inhibited after AAI exposure. AAI induces oxidative stress injury in the kidney, which ultimately leads to inflammation and tubular epithelial cell apoptosis. After LYC intervened in the body, it activated Nrf2 nuclear translocation and its downstream HO-1 and NQO1 antioxidant signaling pathways. LYC inhibited ROS production by renal tubular epithelial cells, and alleviated mitochondrial damage. LYC further modulated the TNF-α/NF-κB signaling cascade, thereby reduced the accumulation of inflammatory factors in the renal interstitium. Moreover, LYC was able to up-regulate the expression of Bcl-2, down-regulate Bax expression and inhibit the activation of cleaved forms of Caspase-9 and Caspase-3, which finally attenuated the apoptosis of the mitochondrial pathway induced by AAI exposure. It was concluded that lycopene was able to activate the Nrf2 antioxidant signaling pathway to maintain the homeostasis of renal oxidative stress and ultimately attenuated renal inflammatory response and apoptosis. These results suggested that lycopene can be used as a drug to relieve AAN.