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The effect of α-phenyl-tert-butyl nitrone (PBN) on free radical formation in transient focal ischaemia measured by microdialysis and 3,4-dihydroxybenzoate formation

Gidö, Gunilla LU ; Cronberg, T. LU and Wieloch, Tadeusz LU (2000) In Acta Physiologica Scandinavica 168(2). p.277-285
Abstract

α-phenyl-tert-butyl nitrone (PBN) reduces infarct size, improves recovery of brain energy metabolism and delays the secondary increase in extracellular potassium after focal ischaemia, presumably by trapping OH radicals. We investigated the effect of PBN on the formation of 3,4-dihydroxybenzoic acid (3,4-DHBA) as a measure of OH radical formation, during and following middle cerebral artery occlusion (MCAO). Rats, subjected to 2 h of ischaemia followed by 3 h of recirculation, were injected with either vehicle or PBN (100 mg kg
-1 i.p.) prior to MCAO or immediately after recirculation, respectively. The in vivo microdialysis technique was used to collect samples for analysis of 3,4-DHBA by HPLC.... (More)

α-phenyl-tert-butyl nitrone (PBN) reduces infarct size, improves recovery of brain energy metabolism and delays the secondary increase in extracellular potassium after focal ischaemia, presumably by trapping OH radicals. We investigated the effect of PBN on the formation of 3,4-dihydroxybenzoic acid (3,4-DHBA) as a measure of OH radical formation, during and following middle cerebral artery occlusion (MCAO). Rats, subjected to 2 h of ischaemia followed by 3 h of recirculation, were injected with either vehicle or PBN (100 mg kg
-1 i.p.) prior to MCAO or immediately after recirculation, respectively. The in vivo microdialysis technique was used to collect samples for analysis of 3,4-DHBA by HPLC. The basal levels of 3,4-DHBA were 56-77 nmol L
-1 in the four groups. During ischaemia, the formation of 3,4-DHBA decreased by about 50% in all groups. Upon recirculation, a 3-fold rise in 3,4-DHBA formation was seen. At 2 h of recirculation the mean value of 3,4-DHBA in the pretreated, vehicle-injected animals was 125 ± 18 nmol L
-1 and in the PBN-injected 145 ± 48 nmol L
-1 respectively. When the animals were treated after MCAO either with vehicle or PBN the values at 2 h recirculation were 155 ± 148 and 189 ± 145 nmol L
-1, respectively. No statistically significant difference between vehicle- and PBN-injected groups was seen. We conclude that during reperfusion following MCAO, hydroxyl radical formation increases. The increase is not ameliorated by PBN which suggests that PBN does not protect the brain by a general scavenging of OH radicals, although tissue specific actions cannot be excluded.

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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Brain, Focal ischaemia, Free radicals, PBN, Rat
in
Acta Physiologica Scandinavica
volume
168
issue
2
pages
9 pages
publisher
Wiley-Blackwell
external identifiers
  • Scopus:0034107744
ISSN
0001-6772
DOI
10.1046/j.1365-201X.2000.00657.x
language
English
LU publication?
yes
id
82f0a4c3-2cc8-4500-a7cd-c28874d77091
date added to LUP
2016-10-05 19:01:37
date last changed
2016-10-10 14:07:13
@misc{82f0a4c3-2cc8-4500-a7cd-c28874d77091,
  abstract     = {<p>α-phenyl-tert-butyl nitrone (PBN) reduces infarct size, improves recovery of brain energy metabolism and delays the secondary increase in extracellular potassium after focal ischaemia, presumably by trapping OH radicals. We investigated the effect of PBN on the formation of 3,4-dihydroxybenzoic acid (3,4-DHBA) as a measure of OH radical formation, during and following middle cerebral artery occlusion (MCAO). Rats, subjected to 2 h of ischaemia followed by 3 h of recirculation, were injected with either vehicle or PBN (100 mg kg<br>
                        <sup>-1</sup> i.p.) prior to MCAO or immediately after recirculation, respectively. The in vivo microdialysis technique was used to collect samples for analysis of 3,4-DHBA by HPLC. The basal levels of 3,4-DHBA were 56-77 nmol L<br>
                        <sup>-1</sup> in the four groups. During ischaemia, the formation of 3,4-DHBA decreased by about 50% in all groups. Upon recirculation, a 3-fold rise in 3,4-DHBA formation was seen. At 2 h of recirculation the mean value of 3,4-DHBA in the pretreated, vehicle-injected animals was 125 ± 18 nmol L<br>
                        <sup>-1</sup> and in the PBN-injected 145 ± 48 nmol L<br>
                        <sup>-1</sup> respectively. When the animals were treated after MCAO either with vehicle or PBN the values at 2 h recirculation were 155 ± 148 and 189 ± 145 nmol L<br>
                        <sup>-1</sup>, respectively. No statistically significant difference between vehicle- and PBN-injected groups was seen. We conclude that during reperfusion following MCAO, hydroxyl radical formation increases. The increase is not ameliorated by PBN which suggests that PBN does not protect the brain by a general scavenging of OH radicals, although tissue specific actions cannot be excluded.</p>},
  author       = {Gidö, Gunilla and Cronberg, T. and Wieloch, Tadeusz},
  issn         = {0001-6772},
  keyword      = {Brain,Focal ischaemia,Free radicals,PBN,Rat},
  language     = {eng},
  number       = {2},
  pages        = {277--285},
  publisher    = {ARRAY(0x7fb2230)},
  series       = {Acta Physiologica Scandinavica},
  title        = {The effect of α-phenyl-tert-butyl nitrone (PBN) on free radical formation in transient focal ischaemia measured by microdialysis and 3,4-dihydroxybenzoate formation},
  url          = {http://dx.doi.org/10.1046/j.1365-201X.2000.00657.x},
  volume       = {168},
  year         = {2000},
}