MICRONIZATION ENHANCES THE PROTECTIVE EFFECT OF PURIFIED FLAVONOID FRACTION AGAINST POSTISCHAEMIC MICROVASCULAR INJURY IN THE HAMSTER CHEEK POUCH

SUMMARY 1. The present study was designed to evaluate the effect of micronization on the protective effect of the purified flavonoid fraction (MPFF) on increases in macromolecular permeability induced by ischaemia–reperfusion in the hamster cheek pouch microcirculation. 2. Male hamsters (Mesocricetu...

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Veröffentlicht in:Clinical and experimental pharmacology & physiology 2004-03, Vol.31 (3), p.159-162
Hauptverfasser: Cyrino, Fátima ZGA, Bottino, Daniel A, Lerond, Laurence, Bouskela, Eliete
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creator Cyrino, Fátima ZGA
Bottino, Daniel A
Lerond, Laurence
Bouskela, Eliete
description SUMMARY 1. The present study was designed to evaluate the effect of micronization on the protective effect of the purified flavonoid fraction (MPFF) on increases in macromolecular permeability induced by ischaemia–reperfusion in the hamster cheek pouch microcirculation. 2. Male hamsters (Mesocricetus auratus) were treated orally, twice a day, with vehicle (lactose), MPFF and non‐micronized purified flavonoid fraction (PFF) at 5, 20, 80 and 320 mg/kg per day for 10 consecutive days. On the 11th day, cheek pouches of anaesthetized animals were prepared for intravital microscopy. 3. Local ischaemia was obtained by clamping the neck of the everted pouch and the increase in microvascular permeability was quantified as leakage (leaks) of intravenously injected fluorescein isothiocyanate‐labelled dextran (FITC–dextran 150; MW = 150 000). 4. Reperfusion, after 30 min ischaemia, resulted in an immediate but reversible increase in post‐capillary leakage. The MPFF induced a significant dose‐related reduction in the increased permeability, with 83.4% inhibition compared with control at 320 mg/kg per day (19.2 ± 1.9 vs 115.7 ± 4.1 leaks/cm2; P 
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On the 11th day, cheek pouches of anaesthetized animals were prepared for intravital microscopy. 3. Local ischaemia was obtained by clamping the neck of the everted pouch and the increase in microvascular permeability was quantified as leakage (leaks) of intravenously injected fluorescein isothiocyanate‐labelled dextran (FITC–dextran 150; MW = 150 000). 4. Reperfusion, after 30 min ischaemia, resulted in an immediate but reversible increase in post‐capillary leakage. The MPFF induced a significant dose‐related reduction in the increased permeability, with 83.4% inhibition compared with control at 320 mg/kg per day (19.2 ± 1.9 vs 115.7 ± 4.1 leaks/cm2; P &lt; 0.0001). Non‐micronized PFF was significantly less effective: only 47.9% inhibition compared with control was observed at 320 mg/kg per day (60.3 ± 1.0 vs 115.7 ± 4.1 leaks/cm2; P &lt; 0.0001) and there was no dose–effect relationship. 5. In conclusion, micronization significantly enhances the protective effects of the purified flavonoid fraction on reperfusion injury in the hamster cheek pouch. 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On the 11th day, cheek pouches of anaesthetized animals were prepared for intravital microscopy. 3. Local ischaemia was obtained by clamping the neck of the everted pouch and the increase in microvascular permeability was quantified as leakage (leaks) of intravenously injected fluorescein isothiocyanate‐labelled dextran (FITC–dextran 150; MW = 150 000). 4. Reperfusion, after 30 min ischaemia, resulted in an immediate but reversible increase in post‐capillary leakage. The MPFF induced a significant dose‐related reduction in the increased permeability, with 83.4% inhibition compared with control at 320 mg/kg per day (19.2 ± 1.9 vs 115.7 ± 4.1 leaks/cm2; P &lt; 0.0001). Non‐micronized PFF was significantly less effective: only 47.9% inhibition compared with control was observed at 320 mg/kg per day (60.3 ± 1.0 vs 115.7 ± 4.1 leaks/cm2; P &lt; 0.0001) and there was no dose–effect relationship. 5. In conclusion, micronization significantly enhances the protective effects of the purified flavonoid fraction on reperfusion injury in the hamster cheek pouch. 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dosage</subject><subject>Protective Agents - pharmacology</subject><subject>Regional Blood Flow - drug effects</subject><subject>Reperfusion</subject><subject>Reperfusion Injury - prevention &amp; control</subject><issn>0305-1870</issn><issn>1440-1681</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2004</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqNkc2O0zAUhSMEYsrAKyCv2CVcx06cLFhYxmkMaRLlpwxsrPxKLe10SKai8xi8MUlbDVu8uUfy-e6RzjUMhMHC0_u4tTClYGLXw5YNQC0gPqPW6YWxeP54aSyAgGNij8GN8WYctwDggEteGzfYAfB8x1sYf1ZKZEmsfvBCJTGScchjIXNUhBKlWVJIUai1RDIIJoWSAKVlpgIlP6Mg4uskTtSkMi7ONF9yFecFSpO8ULkIuZy2o3PCmueijHiGVPylzL5P4xwR8lVeyAyJUMqvE1eK8K3xqq92Y_fuOm-NMpCFCM0oWSrBI7OhQKjZ1r7f1zZtKMYuVB1mTtUCrn236d3ebpjdEA8wqVu78oAy4oNXM6etKPM6TAi5NT5c9j4Mh1_HbnzU-83YdLtddd8djqNmmGHHps5k9C7GZjiM49D1-mHY7KvhSWPQ8zn0Vs-t67l1PZ9Dn8-hTxP6_ppxrPdd-w-89j8ZPl0Mvze77um_F2sh01lNvHnhN-Njd3rmq-Gndhlhjv4WL_Wdt0rF-o7piPwFMGab8Q</recordid><startdate>200403</startdate><enddate>200403</enddate><creator>Cyrino, Fátima ZGA</creator><creator>Bottino, Daniel A</creator><creator>Lerond, Laurence</creator><creator>Bouskela, Eliete</creator><general>Blackwell Science Pty</general><scope>BSCLL</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope></search><sort><creationdate>200403</creationdate><title>MICRONIZATION ENHANCES THE PROTECTIVE EFFECT OF PURIFIED FLAVONOID FRACTION AGAINST POSTISCHAEMIC MICROVASCULAR INJURY IN THE HAMSTER CHEEK POUCH</title><author>Cyrino, Fátima ZGA ; Bottino, Daniel A ; Lerond, Laurence ; Bouskela, Eliete</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4034-db99fb24c41160ae175ad01b96cf6f2c72c38013bd2a80473908b75da478e1333</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2004</creationdate><topic>Administration, Oral</topic><topic>Animals</topic><topic>Capillary Permeability - drug effects</topic><topic>Cheek - blood supply</topic><topic>cheek pouch</topic><topic>Cricetinae</topic><topic>Diosmin - administration &amp; dosage</topic><topic>Diosmin - pharmacology</topic><topic>Drug Combinations</topic><topic>hamster</topic><topic>Hesperidin - administration &amp; dosage</topic><topic>Hesperidin - pharmacology</topic><topic>Ischemia - complications</topic><topic>Ischemia - physiopathology</topic><topic>macromolecular permeability</topic><topic>Male</topic><topic>Mesocricetus</topic><topic>Microcirculation - drug effects</topic><topic>micronization</topic><topic>micronized purified flavonoid fraction</topic><topic>Particle Size</topic><topic>Protective Agents - administration &amp; dosage</topic><topic>Protective Agents - pharmacology</topic><topic>Regional Blood Flow - drug effects</topic><topic>Reperfusion</topic><topic>Reperfusion Injury - prevention &amp; control</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Cyrino, Fátima ZGA</creatorcontrib><creatorcontrib>Bottino, Daniel A</creatorcontrib><creatorcontrib>Lerond, Laurence</creatorcontrib><creatorcontrib>Bouskela, Eliete</creatorcontrib><collection>Istex</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Clinical and experimental pharmacology &amp; physiology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Cyrino, Fátima ZGA</au><au>Bottino, Daniel A</au><au>Lerond, Laurence</au><au>Bouskela, Eliete</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>MICRONIZATION ENHANCES THE PROTECTIVE EFFECT OF PURIFIED FLAVONOID FRACTION AGAINST POSTISCHAEMIC MICROVASCULAR INJURY IN THE HAMSTER CHEEK POUCH</atitle><jtitle>Clinical and experimental pharmacology &amp; physiology</jtitle><addtitle>Clin Exp Pharmacol Physiol</addtitle><date>2004-03</date><risdate>2004</risdate><volume>31</volume><issue>3</issue><spage>159</spage><epage>162</epage><pages>159-162</pages><issn>0305-1870</issn><eissn>1440-1681</eissn><abstract>SUMMARY 1. The present study was designed to evaluate the effect of micronization on the protective effect of the purified flavonoid fraction (MPFF) on increases in macromolecular permeability induced by ischaemia–reperfusion in the hamster cheek pouch microcirculation. 2. Male hamsters (Mesocricetus auratus) were treated orally, twice a day, with vehicle (lactose), MPFF and non‐micronized purified flavonoid fraction (PFF) at 5, 20, 80 and 320 mg/kg per day for 10 consecutive days. On the 11th day, cheek pouches of anaesthetized animals were prepared for intravital microscopy. 3. Local ischaemia was obtained by clamping the neck of the everted pouch and the increase in microvascular permeability was quantified as leakage (leaks) of intravenously injected fluorescein isothiocyanate‐labelled dextran (FITC–dextran 150; MW = 150 000). 4. Reperfusion, after 30 min ischaemia, resulted in an immediate but reversible increase in post‐capillary leakage. The MPFF induced a significant dose‐related reduction in the increased permeability, with 83.4% inhibition compared with control at 320 mg/kg per day (19.2 ± 1.9 vs 115.7 ± 4.1 leaks/cm2; P &lt; 0.0001). Non‐micronized PFF was significantly less effective: only 47.9% inhibition compared with control was observed at 320 mg/kg per day (60.3 ± 1.0 vs 115.7 ± 4.1 leaks/cm2; P &lt; 0.0001) and there was no dose–effect relationship. 5. In conclusion, micronization significantly enhances the protective effects of the purified flavonoid fraction on reperfusion injury in the hamster cheek pouch. This improvement is likely to be related to the better absorption of the micronized formulation, which could explain the superior clinical efficacy shown in previous studies.</abstract><cop>Oxford, UK</cop><pub>Blackwell Science Pty</pub><pmid>15008958</pmid><doi>10.1111/j.1440-1681.2004.03974.x</doi><tpages>4</tpages></addata></record>
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subjects Administration, Oral
Animals
Capillary Permeability - drug effects
Cheek - blood supply
cheek pouch
Cricetinae
Diosmin - administration & dosage
Diosmin - pharmacology
Drug Combinations
hamster
Hesperidin - administration & dosage
Hesperidin - pharmacology
Ischemia - complications
Ischemia - physiopathology
macromolecular permeability
Male
Mesocricetus
Microcirculation - drug effects
micronization
micronized purified flavonoid fraction
Particle Size
Protective Agents - administration & dosage
Protective Agents - pharmacology
Regional Blood Flow - drug effects
Reperfusion
Reperfusion Injury - prevention & control
title MICRONIZATION ENHANCES THE PROTECTIVE EFFECT OF PURIFIED FLAVONOID FRACTION AGAINST POSTISCHAEMIC MICROVASCULAR INJURY IN THE HAMSTER CHEEK POUCH
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