The molecular mechanism of aminoguanidine-mediated reduction on the brain edema after surgical brain injury in rats.
The study investigated the effect of aminoguanidine (AG) on inducible nitric oxide synthase (iNOS), aquaporin-4 (AQP4), malondialdehyde (MDA) and glutathione (GSH) levels in surgical brain injury (SBI) in rats. AG (75, 150 and 300 mg/kg, i.p.) was administered immediately following surgical resection. Using an SBI model, the absence of iNOS protein in any brain tested (sham-operated group, SBI group and SBI+AG group) at 24 h after SBI was confirmed by Western blot analysis. The expression of AQP4 protein in brain tissue at the edge of the resection site increased at 24 h after SBI, which could be greatly attenuated by the treatment with AG (150 mg/kg), while AG at the dose of 75 mg/kg or 300 mg/kg had no significant effect on it. In addition, there was a marked decrease of MDA values and a great increase of the GSH levels at 24 h after SBI in SBI+AG (150 mg/kg) group compared with SBI group. Whereas AG (300 mg/kg) elevated oxidative stress compared with SBI group. Our results indicate that the anti-edematous effect of AG observed in our study is dose-dependent and unlikely related to its inhibition effect on iNOS and may attribute to its roles on the regulation of AQP4 expression and antioxidative property at brain tissue after SBI.
Hao
Wei
W
Department of Radiology, The First Affiliated Hospital, China Medical University, Shen yang 110001, Liaoning Province, PR China.
Wu
Xi-qiang
XQ
Xu
Rong-tian
RT
D000818:Animals; D051401:Aquaporin 4 / Q000187:drug effects / Q000378:metabolism; D001929:Brain Edema / Q000188:drug therapy* / Q000209:etiology* / Q000503:physiopathology; D001930:Brain Injuries / Q000150:complications*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004660:Encephalitis / Q000188:drug therapy / Q000503:physiopathology / Q000517:prevention & control; D004791:Enzyme Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D005978:Glutathione / Q000378:metabolism; D006146:Guanidines / Q000494:pharmacology* / Q000627:therapeutic use; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000187:drug effects / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects* / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D015854:Up-Regulation / Q000187:drug effects / Q000502:physiology
D051401:Aquaporin 4; D004791:Enzyme Inhibitors; D006146:Guanidines; D009569:Nitric Oxide; D008315:Malondialdehyde; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat; D005978:Glutathione; C004479:pimagedine