Effects of (−)-nicotine and (−)-cotinine on 6-hydroxydopamine-induced oxidative stress and neurotoxicity: relevance for Parkinson’s disease

• Published in: Biochemical pharmacology 2002-07, Vol.64 (1), p.125-135
• Main Authors: Soto-Otero, Ramón, Méndez-Álvarez, Estefanı́a, Hermida-Ameijeiras, Álvaro, López-Real, Ana Marı́a, Labandeira-Garcı́a, José Luis
• Format: Article
• Language: English
• Subjects: (−)-Cotinine; (−)-Nicotine; 6-Hydroxydopamine; Adrenergic Agents - pharmacology; Analysis of Variance; Animals; Biological and medical sciences; Corpus Striatum - drug effects; Corpus Striatum - metabolism; Cotinine - pharmacology; Disease Models, Animal; Dopaminergic neurotoxicity; Drug Interactions; Drug toxicity and drugs side effects treatment; Female; Male; Medical sciences; Neuropharmacology; Neuroprotective agent; Neurotoxicity Syndromes; Nicotine - pharmacology; Nicotinic Agonists - pharmacology; Oxidative stress; Oxidative Stress - drug effects; Oxidopamine - pharmacology; Parkinsonian Disorders - chemically induced; Parkinsonian Disorders - physiopathology; Parkinson’s disease; Pharmacology. Drug treatments; Rats; Rats, Sprague-Dawley; Toxicity: nervous system and muscle
• ISSN: 0006-2952; 1873-2968
• DOI: 10.1016/S0006-2952(02)01070-5

In view of the apparent controversial properties of (−)-nicotine (NIC) in relation to both oxidative stress and neuroprotection, we studied the effects of NIC on hydroxyl radical ( OH) formation, oxidative stress production by 6-hydroxydopamine (6-OHDA) autoxidation in the presence and absence of ascorbate, and 6-OHDA neurotoxicity. Both NIC and (−)-cotinine (COT) exhibited increased OH production during 6-OHDA autoxidation. Although the same effect was observed in OH generation by the Fenton reaction (H 2O 2+Fe 2+), this reaction was completely prevented with the previous incubation of Fe 2+ with NIC or COT. Furthermore, both NIC and COT demonstrated a capacity to be able to reduce the TBARS formation provoked in rat brain mitochondrial preparations by 6-OHDA autoxidation. This effect is assumed as a consequence of the action of NIC and COT on lipid peroxidation propagation. We treated with NIC (1 mg/kg, i.p.) two 6-OHDA-induced rat models of Parkinson’s disease. However, only in one of these models did we obtain clear evidence of a neuroprotective effect of NIC on nigrostriatal terminals, as revealed by immunohistochemistry against tyrosine hydroxylase. Thus, the antioxidant properties of both NIC and COT in relation to the lipid peroxidation induced by 6-OHDA autoxidation, together with their reported capacity to prevent the Fenton reaction, probably by sequestration of Fe 2+, may contribute to an understanding of its neuroprotective properties. In addition, the reported capacity of both NIC and COT to increase the production of OH by 6-OHDA autoxidation might help explain the controversial observation found under different experimental conditions.