Nitric oxide production and nitric oxide synthase expression in platelets from heroin abusers before and after ultrarapid detoxification.
Prolonged heroin abuse has been associated with neurotoxicity. Thus, the involvement of nitric oxide (NO) in heroin-induced dopaminergic neurotoxicity could be a reasonable explanation for heroin-induced changes in brain. Enzymatically derived NO has been implicated in numerous physiological and pathological processes in the brain. Whereas during development NO participates in growing and maturation processes, excess NO production in the adult in response to inflammation, injury, or trauma, participates in both cell death and repair. The expression and activity of the inducible isoform of NO synthase (iNOS) play a pivotal role in sustained and elevated NO release. Recent evidence suggests that neurons can respond to proinflammatory stimuli and take part in brain inflammation. The effect of heroin abuse on platelet NO production and on expression of iNOS in drug addicts submitted to an ultrarapid detoxification was studied. The NO production was estimated from the nitrite concentration, and nitric oxide synthase was determined by Western blotting analysis. Results showed no difference in nitrite content of resting platelets between heroin abuser and control groups. However, after platelet stimulation, heroin abusers showed significantly lower nitrite values. The Western blotting analysis reinforced these results. After ultrarapid detoxification, platelet nitrite production in heroin abusers showed no differences compared to control subjects. Our results suggest that heroin consumption decreases the iNOS synthase expression and platelet NO production. Detoxification treatment restores these changes.
Batista
Ana
A
Institute of Pharmacology and Experimental Therapeutics, Faculty of Medicine, University of Coimbra, 3004-504, Coimbra, Portugal.
Macedo
Tice
T
Tavares
Paula
P
Ribeiro
Carlos Fontes
CF
Relvas
João
J
Gomes
Piedade
P
Ramalheira
Carlos
C
Botto
Isabel
I
Vale
Luisa
L
Ferreira
Luís
L
Guete
Orlando
O
Ruiz
Guadalupe
G
D000293:Adolescent; D000328:Adult; D001792:Blood Platelets / Q000378:metabolism*; D005260:Female; D006556:Heroin Dependence / Q000097:blood* / Q000534:rehabilitation*; D006801:Humans; D008658:Inactivation, Metabolic; D008297:Male; D008875:Middle Aged; D009569:Nitric Oxide / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000097:blood*; D052247:Nitric Oxide Synthase Type II; D013997:Time Factors
D009569:Nitric Oxide; C496319:NOS2 protein, human; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II