Protective efficacy of crocetin and its nanoformulation against cyclosporine A-mediated toxicity in human embryonic kidney cells

This study is aimed to formulate crocetin-loaded lipid Nanoparticles (NPs) and to evaluate its antioxidant properties in a cyclosporine A-mediated toxicity in Human Embryonic Kidney (HEK-293) cells in vitro.Main methodsCrocetin-loaded NPs were prepared followed by physicochemical characterization. In vitro protective efficacy of crocetin and crocetin loaded NPs was investigated in cyclosporine A-mediated toxicity in HEK-293 cells by assessing free radical scavenging, DNA Nicking, cytotoxicity, intracellular Reactive oxygen species (ROS) inhibition, Mitochondrial membrane potential (MMPs) loss and evaluating the activity and expression of antioxidant enzymes and non-enzyme level. Further, we have studied the mechanism of protective activity of crocetin either native or in NPs by studying the expression of phase II detoxifying proteins (HO-1) via Nrf2 mediated regulation.Key findingsOur results showed that pretreatment with crocetin and crocetin-loaded NPs attenuated the cyclosporine A-mediated toxicity, ROS production and exhibited enhance free radical scavenging ability and cytoprotective activity. Further, the treatment prevented MMPs loss by directly scavenging the ROS and restored the antioxidant enzyme network with normalization of HO-1 expression by inhibiting nuclear translocation of Nrf2.SignificancePretreatment of crocetin and crocetin-loaded NPs provided pronounce protective effect against cyclosporine A-mediated toxicity in HEK-293 cells by nullifying the ROS format...
Source: Life Sciences - Category: Biology Source Type: research