Selegiline modulates nitric oxide and peroxynitrite production by polymorphonuclear leukocytes in Parkinson’s disease

GATTO EM; RIOBÓ N; CARRERAS MC; PODEROSO JJ

Milán, Italia

Congreso; Ninth Meeting of the European Neurological Society; 1999

Selegiline is a selective monoamino oxidase type B inhibitor that delays the progression of Parkinson’s disease (PD) and spares levadopa dose. The finding of tyrosine nitration in Lewy bodies supports a role of nitric oxide (NO), and its byproduct peroxynitrite (ONOO-), in the pathogenesis of PD. In accord, selegiline protects dopaminergic cells from apoptosis induced by NO and ONOO-. We previously reported an increased NO and hydrogen peroxide (H2O2) production rates by phorbol-12-myristate-13acetate (PMA) activated polymorphonuclear cells (PMN) from PD patients. The objective was to study the NO and H2O2 production rate and protein tyrosine nitration in PMN of 5 PD patients before and after 1 month of 10 mg/day selegiline intake and 10 age-matched controls (mean±SEM: 49,8 ± 1 vs 50 ± 1 years). NO was measured by oxynyoglobin oxidation and H2O2 by fluorometric assay. Selegiline decreased the previously enhanced NO and H2O2 production of PMA-activated PMN from PD patients (NO: PD 0,89±0,09*; PD+selegiline 0,63±0,09, controls 0,56±0,09; H2O2: PD 4,25±0,17, PD+selegiline 2,5±0,17, controls 3,15±0,47; *p<0,05), as well as the augmented tyrosine nitration determined by Western blot. These results suggest that neuroprotection by selegiline could be related to a diminished NO and ONOO- production.