eprintid: 10118844
rev_number: 17
eprint_status: archive
userid: 608
dir: disk0/10/11/88/44
datestamp: 2021-01-15 15:15:32
lastmod: 2021-10-20 23:30:31
status_changed: 2021-01-15 15:15:32
type: article
metadata_visibility: show
creators_name: Freitas, F
creators_name: Tibiriçá, E
creators_name: Singh, M
creators_name: Fraser, PA
creators_name: Mann, GE
title: Redox Regulation of Microvascular Permeability: IL-1β Potentiation of Bradykinin-Induced Permeability Is Prevented by Simvastatin
ispublished: pub
divisions: UCL
divisions: B02
divisions: C08
divisions: D09
divisions: G02
keywords: NADPH oxidase, bradykinin, interleukin 1β, microvascular permeability, reactive oxygen species, simvastatin
note: This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited
abstract: Antioxidant effects of statins have been implicated in the reduction in microvascular permeability and edema formation in experimental and clinical studies. Bradykinin (Bk)-induced increases in microvascular permeability are potentiated by IL-1β; however, no studies have examined the protection afforded by statins against microvascular hyperpermeability. We investigated the effects of simvastatin pretreatment on albumin-fluorescein isothiocyanate conjugate (FITC-albumin) permeability in post-capillary venules in rat cremaster muscle. Inhibition of nitric oxide synthase with L-NAME (10µM) increased basal permeability to FITC-albumin, which was abrogated by superoxide dismutase and catalase. Histamine-induced (1 µM) permeability was blocked by L-NAME but unaffected by scavenging reactive oxygen species with superoxide dismutase (SOD) and catalase. In contrast, bradykinin-induced (1-100 nM) permeability increases were unaffected by L-NAME but abrogated by SOD and catalase. Acute superfusion of the cremaster muscle with IL-1β (30 pM, 10 min) resulted in a leftward shift of the bradykinin concentration-response curve. Potentiation by IL-1β of bradykinin-induced microvascular permeability was prevented by the nicotinamide adenine dinucleotide phosphate oxidase (NADPH oxidase) inhibitor apocynin (1 µM). Pretreatment of rats with simvastatin (5 mg·kg-1, i.p.) 24 h before permeability measurements prevented the potentiation of bradykinin permeability responses by IL-1β, which was not reversed by inhibition of heme oxygenase-1 with tin protoporphyrin IX (SnPP). This study highlights a novel mechanism by which simvastatin prevents the potentiation of bradykinin-induced permeability by IL-1β, possibly by targeting the assembly of NADPH oxidase subunits. Our findings highlight the therapeutic potential of statins in the prevention and treatment of patients predisposed to inflammatory diseases.
date: 2020-12-14
date_type: published
official_url: http://dx.doi.org/10.3390/antiox9121269
oa_status: green
full_text_type: pub
pmcid: PMC7764912
language: eng
primo: open
primo_central: open_green
verified: verified_manual
elements_id: 1838978
doi: 10.3390/antiox9121269
pii: antiox9121269
publication_declined: 2021-02-24T23:28:02GMT
lyricists_name: Santos Simoes De Freitas, Felipe
lyricists_id: FSANT92
actors_name: Flynn, Bernadette
actors_id: BFFLY94
actors_role: owner
full_text_status: public
publication: Antioxidants
volume: 9
number: 12
article_number: 1269
event_location: Switzerland
citation:        Freitas, F;    Tibiriçá, E;    Singh, M;    Fraser, PA;    Mann, GE;      (2020)    Redox Regulation of Microvascular Permeability: IL-1β Potentiation of Bradykinin-Induced Permeability Is Prevented by Simvastatin.                   Antioxidants , 9  (12)    , Article 1269.  10.3390/antiox9121269 <https://doi.org/10.3390/antiox9121269>.       Green open access   
 
document_url: https://discovery.ucl.ac.uk/id/eprint/10118844/1/antioxidants-09-01269.pdf