Simvastatin-loaded nano-niosomes efficiently downregulates the MAPK-NF-κB pathway during the acute phase of myocardial ischemia-reperfusion injury.
Drug delivery system
MAPK-NF-κB pathway
Myocardial ischemia/reperfusion injury
Nano-niosomes
Simvastatin
Journal
Molecular biology reports
ISSN: 1573-4978
Titre abrégé: Mol Biol Rep
Pays: Netherlands
ID NLM: 0403234
Informations de publication
Date de publication:
Nov 2022
Nov 2022
Historique:
received:
23
04
2022
accepted:
18
08
2022
revised:
10
08
2022
pubmed:
13
9
2022
medline:
2
11
2022
entrez:
12
9
2022
Statut:
ppublish
Résumé
Simvastatin can potentially mitigate acute inflammatory phase of myocardial ischemia-reperfusion injury. However, these effects negatively influenced by its poor bioavailability, low water solubility and high metabolism. Here, we investigated the effects of SIM-loaded nano-niosomes on a rat model of MI/R injury to find a drug delivery method to tackle the barriers. Nano-niosomes' characteristics were identified using dynamic light scattering and transmission electron microscopy. Fifty male Wistar rats were divided into five groups: Sham; MI/R; MI/R + nano-niosome; MI/R + SIM; MI/R + SIM-loaded nano-niosomes. Left anterior descending artery was ligated for 45 min, and 3 mg/kg SIM, nano-niosomes, or SIM-loaded nano-niosomes was intramyocardially injected ten min before the onset of reperfusion. ELISA assay was used to assess cardiac injury markers (cTnI, CK-MB) and inflammatory cytokines (TNF-α, IL-6, TGF-β, MPC-1). Expression level of MAPK-NF-κB and histopathological changes were evaluated by western blot and hematoxylin & eosin staining, respectively. the size of nano-niosome was 137 nm, reached to 163 nm when simvastatin was loaded. To achieve optimized niosomes span 80, a drug/cholesterol ratio of 0.4 and seven min of sonication time was applied. Optimized entrapment efficiency of SIM-loaded nano-niosomes was 98.21%. Inflammatory cytokines and the expression level of MAPK and NF-κB were reduced in rats receiving SIM-loaded nano-niosomes compared to MI/R + SIM and MI/R + SIM-loaded nano-niosomes. Our results showed that SIM-loaded nano-niosomes could act more efficiently than SIM in alleviating the acute inflammatory response of reperfusion injury via downregulating the activation of MAPK-NF-κB.
Sections du résumé
BACKGROUND
BACKGROUND
Simvastatin can potentially mitigate acute inflammatory phase of myocardial ischemia-reperfusion injury. However, these effects negatively influenced by its poor bioavailability, low water solubility and high metabolism. Here, we investigated the effects of SIM-loaded nano-niosomes on a rat model of MI/R injury to find a drug delivery method to tackle the barriers.
METHODS
METHODS
Nano-niosomes' characteristics were identified using dynamic light scattering and transmission electron microscopy. Fifty male Wistar rats were divided into five groups: Sham; MI/R; MI/R + nano-niosome; MI/R + SIM; MI/R + SIM-loaded nano-niosomes. Left anterior descending artery was ligated for 45 min, and 3 mg/kg SIM, nano-niosomes, or SIM-loaded nano-niosomes was intramyocardially injected ten min before the onset of reperfusion. ELISA assay was used to assess cardiac injury markers (cTnI, CK-MB) and inflammatory cytokines (TNF-α, IL-6, TGF-β, MPC-1). Expression level of MAPK-NF-κB and histopathological changes were evaluated by western blot and hematoxylin & eosin staining, respectively.
RESULTS
RESULTS
the size of nano-niosome was 137 nm, reached to 163 nm when simvastatin was loaded. To achieve optimized niosomes span 80, a drug/cholesterol ratio of 0.4 and seven min of sonication time was applied. Optimized entrapment efficiency of SIM-loaded nano-niosomes was 98.21%. Inflammatory cytokines and the expression level of MAPK and NF-κB were reduced in rats receiving SIM-loaded nano-niosomes compared to MI/R + SIM and MI/R + SIM-loaded nano-niosomes.
CONCLUSION
CONCLUSIONS
Our results showed that SIM-loaded nano-niosomes could act more efficiently than SIM in alleviating the acute inflammatory response of reperfusion injury via downregulating the activation of MAPK-NF-κB.
Identifiants
pubmed: 36097124
doi: 10.1007/s11033-022-07891-3
pii: 10.1007/s11033-022-07891-3
doi:
Substances chimiques
NF-kappa B
0
Simvastatin
AGG2FN16EV
Liposomes
0
Cytokines
0
Types de publication
Journal Article
Retracted Publication
Langues
eng
Sous-ensembles de citation
IM
Pagination
10377-10385Commentaires et corrections
Type : RetractionIn
Informations de copyright
© 2022. The Author(s), under exclusive licence to Springer Nature B.V.
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