Cabergoline scavenges peroxynitrite enhanced by l‐DOPA therapy in patients with Parkinson's disease

Abstract

Long-term or high-dose L-DOPA therapy in patients with Parkinson's disease (PD) may accelerate degeneration of dopaminergic neurons, possibly by increasing oxidative stress. To investigate the effects of cabergoline on peroxynitrite-mediated oxidative damage caused by L-DOPA, the concentration of 3-nitrotyrosine in cerebrospinal fluid (CSF) of 18 PD patients was compared with that in 20 normal controls. The concentration of 3-nitrotyrosine in patients following L-DOPA therapy was significantly higher than in untreated PD patients and controls. On the other hand, the concentration in PD patients after cabergoline therapy was significantly lower than in PD patients after L-DOPA therapy alone. These data suggest that cabergoline scavenges peroxynitrite induced by L-DOPA in patients with PD.

Nitrosative and cognitive effects of chronic l-DOPA administration in rats with intra-nigral 6-OHDA lesion

“…Some clinical studies show an increase of 3-NT in the cerebrospinal fluid of these patients (Isobe et al, 2006), while preclinical studies have clearly demonstrated that a single administration of L-DOPA, either alone or with Carbidopa, can induce NS (Calabrese et al, 2007), thus demonstrating that L-DOPA induces NS and could, therefore, cause severe neuronal toxicity.…”

Original article Cabergoline protects dopaminergic neurons against rotenone-induced cell death in primary mesencephalic cell culture

“…Since DHE is predominantly a superoxide indicator, we detected that cabergoline is also able to reduce general oxidative stress induced by rotenone even when the culture is only pre-incubated with the agonist. Isobe et al found that cabergoline scavenged peroxynitrite induced by levodopa in PD patients [12]. Although cabergoline increased GSH synthesis in mesencephalic cell cultures, its neuroprotective effect against rotenone toxicity was not dependent on GSH synthesis, as pre-treatment of mesencephalic cell cultures with the GSH biosyn thesis inhibitor BSO did not prevent protection of dopaminergic neurons afforded by cabergoline (Fig.…”

Oxidative Stress and Microglial Cells in Parkinson's Disease

“…Excess production of reactive oxygen and nitrogen species in PD is thought to damage lipids, proteins, and DNA as shown postmortem by high levels of lipid peroxidation products, oxidized and damaged proteins, as well as oxidized DNA in the CNS of PD patients [18, 93]. PN-modified proteins have been found to accumulate in the Lewy bodies of the cells in PD brains and PN has been shown to inhibit complex-I-mediated cellular respiration [82, 91, 92, 94–96]. …”