Combined treatment with atorvastatin and imipenem improves survival and vascular functions in mouse model of sepsis
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Title |
Combined treatment with atorvastatin and imipenem improves survival and vascular functions in mouse model of sepsis
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Creator |
Choudhury S, Kannan K, Pule Addison M, Darzi SA, Singh V, Singh TU, Thangamalai R, Dash JR, Parida S, Debroy B, Paul A, Mishra SK
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Subject |
Atorvastatin; GRK2; Imipenem; Sepsis; eNOS; α(1D) adrenoceptor.
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Description |
Not Available
We have recently reported that pre-treatment, but not the post-treatment with atorvastatin showed survival benefit and improved hemodynamic functions in cecal ligation and puncture (CLP) model of sepsis in mice. Here we examined whether combined treatment with atorvastatin and imipenem after onset of sepsis can prolong survival and improve vascular functions. At 6 and 18h after sepsis induction, treatment with atorvastatin plus imipenem, atorvastatin or imipenem alone or placebo was initiated. Ex vivo experiments were done on mouse aorta to examine the vascular reactivity to nor-adrenaline and acetylcholine and mRNA expressions of α1D AR, GRK2 and eNOS. Atorvastatin plus imipenem extended the survival time to 56.00±4.62h from 20.00±1.66h observed in CLP mice. The survival time with atorvastatin or imipenem alone was 20.50±1.89h and 27.00±4.09h, respectively. The combined treatment reversed the hyporeactivity to nor-adrenaline through preservation of α1D AR mRNA/protein expression and reversal of α1D AR desensitization mediated by GRK2/Gβγ pathway. The treatment also restored endothelium-dependent relaxation to ACh through restoration of aortic eNOS mRNA expression and NO availability. In conclusion, combined treatment with atorvastatin and imipenem exhibited survival benefit and improved vascular functions in septic mice. Not Available |
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Date |
2023-05-18T04:54:11Z
2023-05-18T04:54:11Z 2015-03-03 |
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Type |
Article
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Identifier |
Choudhury S, Kannan K, Pule Addison M, Darzi SA, Singh V, Singh TU, Thangamalai R, Dash JR, Parida S, Debroy B, Paul A, Mishra SK. Combined treatment with atorvastatin and imipenem improves survival and vascular functions in mouse model of sepsis. Vascul Pharmacol. 2015 Aug;71:139-50. doi: 10.1016/j.vph.2015.03.012. Epub 2015 Apr 10. PMID: 25869507.
Not Available http://krishi.icar.gov.in/jspui/handle/123456789/77569 |
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Language |
English
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Relation |
Not Available;
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Publisher |
Elsevier
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