Beneficial effects of n-acetylcysteine on ischaemic brain injury.
1. Nitric oxide (NO), peroxynitrite, formed from NO and superoxide anion, poly (ADP-ribole) synthetase have been implicated as mediators of neuronal damage following focal ischaemia. Here we have investigated the effects of n-acetylcysteine (NAC) treatment in Mongolian gerbils subjected to cerebral ischaemia. 2. Treatment of gerbils with NAC (20 mg kg(-1) 30 min before reperfusion and 1, 2 and 6 h after reperfusion) reduced the formation of post-ischaemic brain oedema, evaluated by water content. 3. NAC also attenuated the increase in the brain levels of malondialdehyde (MDA) and the increase in the hippocampus of myeloperoxidase (MPO) caused by cerebral ischaemia. 4. Positive staining for nitrotyrosine was found in the hippocampus in Mongolian gerbils subjected to cerebral ischaemia. Hippocampus tissue sections from Mongolian gerbils subjected to cerebral ischaemia also showed positive staining for poly (ADP-ribose) synthetase (PARS). The degree of staining for nitrotyrosine and for PARS were markedly reduced in tissue sections obtained from animals that received NAC. 5. NAC treatment increased survival and reduced hyperactivity linked to neurodegeneration induced by cerebral ischaemia and reperfusion. 6. Histological observations of the pyramidal layer of CA1 showed a reduction of neuronal loss in animals that received NAC. 7. These results show that NAC improves brain injury induced by transient cerebral ischaemia.
Cuzzocrea
S
S
Institute of Pharmacology, School of Medicine, University of Messina, Torre Biologica, Policlinico Universitario Via C. Valeria, Italy. salvator@imeuniv.unime.it
Mazzon
E
E
Costantino
G
G
Serraino
I
I
Dugo
L
L
Calabrò
G
G
Cucinotta
G
G
De Sarro
A
A
Caputi
A P
AP
D000111:Acetylcysteine / Q000494:pharmacology*; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D001929:Brain Edema / Q000473:pathology / Q000517:prevention & control; D002545:Brain Ischemia / Q000378:metabolism / Q000503:physiopathology / Q000517:prevention & control*; D016166:Free Radical Scavengers / Q000494:pharmacology*; D005849:Gerbillinae; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D009043:Motor Activity / Q000187:drug effects; D009569:Nitric Oxide / Q000378:metabolism; D009195:Peroxidase / Q000187:drug effects / Q000378:metabolism; D011065:Poly(ADP-ribose) Polymerases / Q000187:drug effects / Q000378:metabolism; D015427:Reperfusion Injury / Q000378:metabolism / Q000503:physiopathology / Q000517:prevention & control*; D013997:Time Factors; D014443:Tyrosine / Q000031:analogs & derivatives / Q000187:drug effects / Q000378:metabolism
D016166:Free Radical Scavengers; D009569:Nitric Oxide; C002744:3-nitrotyrosine; D014443:Tyrosine; D008315:Malondialdehyde; D009195:Peroxidase; D011065:Poly(ADP-ribose) Polymerases; D000111:Acetylcysteine