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Int J Nanomedicine ; 15: 9115-9124, 2020.
Article in English | MEDLINE | ID: mdl-33244230

ABSTRACT

BACKGROUND: Apigenin is known to have a broad-spectrum efficacy in oxidative stress and conditions due to inflammation, although weak absorption, fast metabolic rate and a fast elimination (systemic) limit the pharmacological efficacy of this drug. Hence, we propose the usage of highly bioavailable Apigenin-solid lipid nanoparticles (SLNPs) to recognize such limitations. The defensive function of Apigenin-SLNPs on renal damage induced by streptozotocin (STZ) in animals was studied. MATERIALS AND METHODS: We initially injected the rats with 35 mg kg-1 streptozocin intraperitoneally, and after 7 days, the rats were then injected 150 mg kg-1 of metformin intragastrically followed by a once-daily intragastric dose of Apigenin-SLNP (25 or 50 mg kg-1) for a continuous period of 30 days. We then measured the level of insulin and blood glucose, superoxide dismutase, catalase and malondialdehyde in the tissues of the kidney. We also observed messenger-RNA expression of Interleukin-1ß, Interleukin-6 and Tumor Necrosis Factor-alpha in renal tissue through RT-PCR technique. Moreover, H&E staining and Western blotting observed the histopathological variations and protein expression of nuclear factor erythroid 2-related factor 2/heme oxygenase/Nuclear Factor-κB signaling pathway, respectively. RESULTS: An enhancement in the expressing of nuclear factor erythroid 2-related factor 2 and heme oxygenase-1 and a suppression in the expression of Nuclear Factor-κB occurred due to Apigenin-SLNPs treatment, which was a result of the protective mechanism of Apigenin-SLNPs which is because of not only its anti-inflammatory function (by inhibition of release of inflammatory factors) but also their anti-oxidant activity (through reduction of lipid peroxidation production). CONCLUSION: We found that a protective effect on diabetic nephropathy was shown due to Apigenin-SLNPs, in rats induced with streptozocin maybe through the pathway of nuclear factor erythroid 2-related factor 2/heme oxygenase-1/Nuclear Factor-κB.


Subject(s)
Apigenin/pharmacology , Diabetic Nephropathies/drug therapy , Heme Oxygenase (Decyclizing)/metabolism , NF-E2-Related Factor 2/metabolism , Nanoparticles/administration & dosage , Signal Transduction/drug effects , Animals , Antioxidants/administration & dosage , Antioxidants/pharmacology , Apigenin/administration & dosage , Diabetes Mellitus, Experimental/complications , Diabetes Mellitus, Experimental/drug therapy , Diabetes Mellitus, Experimental/metabolism , Diabetic Nephropathies/chemically induced , Diabetic Nephropathies/metabolism , Drug Delivery Systems , Kidney/drug effects , Kidney/metabolism , Kidney/pathology , Lipids/chemistry , Male , Malondialdehyde/metabolism , NF-kappa B/metabolism , Nanoparticles/chemistry , Oxidative Stress/drug effects , Rats , Streptozocin , Superoxide Dismutase/metabolism
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