Influence of 5-aminoisoquinolin-1-one (5-AIQ) on neutrophil chemiluminescence in rats with transient and prolonged focal cerebral ischemia and after reperfusion.
Stimulation of neutrophils by different factors increases their oxidative activity and the free radicals produced can report on the degree of activation. Poly(adenosine 5'-diphosphate ribose)polymerase-1 (PARP-1), a nuclear enzyme activated by strand breaks in DNA, plays an important role in the tissue injury associated with ischaemia-reperfusion injury and inflammation. 5-aminoisoquinolin-1-one (5-AIQ) is a potent inhibitor of PARP-1 activity in vitro and in vivo in rats. Acute (80 min) and prolonged (24h) focal cerebral ischaemia was induced in rats by obstruction of the median cerebral artery, with or without reperfusion, with or without administration of 5-AIQ. The oxidative activity of neutrophils was measured by chemiluminescence. Administration of 5-AIQ.HCl (3.0 mg kg(-1) b.w. - i.v.) caused a significant decrease in the oxidative activity of neutrophils in the group which had experienced chronic ischaemia for 24h but had no significant effect in the group which had received 80 min ischaemia, when compared to the control group. Increase of the oxidative activity of neutrophils was confirmed in rats with prolonged cerebral ischaemia, followed by reperfusion. 5-AIQ probably may decrease this activity through inhibition of PARP-1 in focus of local ischaemia as well as hence lowering the expression of inflammatory mediators by activated neutrophils.
Hendryk
S
S
Department of Neurosurgery, Medical University of Silesia, Katowice, Poland.
Czuba
Z P
ZP
Jedrzejowska-Szypulka
H
H
Szliszka
E
E
Phillips
V A
VA
Threadgill
M D
MD
Krol
W
W
D000818:Animals; D002545:Brain Ischemia / Q000188:drug therapy* / Q000503:physiopathology; D053960:DNA Breaks; D004195:Disease Models, Animal; D005609:Free Radicals / Q000378:metabolism; D007546:Isoquinolines / Q000494:pharmacology*; D008163:Luminescent Measurements; D008297:Male; D009504:Neutrophils / Q000187:drug effects* / Q000378:metabolism; D000071137:Poly (ADP-Ribose) Polymerase-1; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000188:drug therapy / Q000503:physiopathology; D013997:Time Factors
C411425:5-aminoisoquinolinone; D005609:Free Radicals; D007546:Isoquinolines; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; C499322:Parp1 protein, rat; D000071137:Poly (ADP-Ribose) Polymerase-1