Aspirin inhibits stress-induced increase in plasma glutamate, brain oxidative damage and ATP fall in rats.
The precise mechanisms by which stress induces brain damage are still being elucidated. The high-output, inducible isoform of nitric oxide (NO) synthase (iNOS) is expressed in rat brain after immobilisation stress and its inhibition protects against cell damage in this condition. We have hereby explored some mechanisms involved in iNOS expression and studied the effects of aspirin, a NSAID with neuroprotective actions, in this model. Acute (6 h) stress exposure in rats caused brain expression of iNOS, an increase in plasma glutamate and brain TNF-alpha, induction of oxidative indicators in brain and a fall in brain ATP levels. Prior administration of aspirin (10 mg/kg i.p.) inhibited all these effects caused by stress, suggesting possible therapeutic implications of this drug in this condition.
De Cristóbal
Javier
J
Departamento de Farmacología, Facultad de Medicina, Universidad Complutense, Madrid 28040, Spain.
Madrigal
José L M
JL
Lizasoain
Ignacio
I
Lorenzo
Pedro
P
Leza
Juan C
JC
Moro
María A
MA
D000255:Adenosine Triphosphate / Q000378:metabolism*; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D001241:Aspirin / Q000494:pharmacology*; D001921:Brain / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology*; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism; D018698:Glutamic Acid / Q000097:blood*; D007103:Immobilization; D008297:Male; D009410:Nerve Degeneration / Q000209:etiology / Q000473:pathology*; D018696:Neuroprotective Agents / Q000494:pharmacology*; D019001:Nitric Oxide Synthase / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II; D010084:Oxidation-Reduction; D051381:Rats; D017208:Rats, Wistar; D012016:Reference Values; D013312:Stress, Physiological / Q000150:complications / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D000894:Anti-Inflammatory Agents, Non-Steroidal; D018696:Neuroprotective Agents; D014409:Tumor Necrosis Factor-alpha; D018698:Glutamic Acid; D000255:Adenosine Triphosphate; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat; D001241:Aspirin