期刊
LIFE SCIENCES
卷 216, 期 -, 页码 39-48出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.lfs.2018.11.027
关键词
Crocetin; Nanoparticle; Cyclosporine; Cytotoxicity; ROS; Antioxidant activity
资金
- Department of Biotechnology, Govt. of India
Aim: 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 methods: Crocetin-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 HEK293 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 findings: Our 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 heme oxygenase-1 (HO-1) expression by inhibiting nuclear translocation of Nrf2. Significance: Pretreatment of crocetin and crocetin-loaded NPs provided pronounce protective effect against cyclosporine A-mediated toxicity in HEK-293 cells by nullifying the ROS formation and restored antioxidant network through inhibition of Nrf2 translocation and followed by expression of HO-1. Such an approach may be anticipated to be beneficial for antioxidant therapy.
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