7-chloro-4-(phenylselanyl) quinoline prevents dopamine depletion in a Drosophila melanogaster model of Parkinson's-like disease

Shanda de Freitas Couto; Stífani Machado Araujo; Vandreza Cardoso Bortolotto; Marcia Rósula Poetini; Franciane Cabral Pinheiro; Elize Aparecida Santos Musachio; Luana Barreto Meichtry; Manoela do Sacramento; Diego Alves; Diogo La Rosa Novo; Márcia Foster Mesko; Marina Prigol

doi:10.1016/j.jtemb.2018.10.015

7-chloro-4-(phenylselanyl) quinoline prevents dopamine depletion in a Drosophila melanogaster model of Parkinson's-like disease

J Trace Elem Med Biol. 2019 Jul:54:232-243. doi: 10.1016/j.jtemb.2018.10.015. Epub 2018 Oct 15.

Affiliations

¹ Laboratório de Avaliações Farmacológicas e Toxicológicas Aplicadas às Moléculas Bioativas, LaftamBio Pampa, Universidade Federal do Pampa, Campus Itaqui, Rua Luiz Joaquim de Sá Britto, s/n - Bairro: Promorar, Itaqui, Rio Grande do Sul, CEP 97650-000, Brazil; Department of Nutrition, Universidade Federal do Pampa, Campus Itaqui, Rua Luiz Joaquim de Sá Britto, s/n - Bairro: Promorar, Itaqui, Rio Grande do Sul, CEP 97650-000, Brazil.
² Laboratório de Avaliações Farmacológicas e Toxicológicas Aplicadas às Moléculas Bioativas, LaftamBio Pampa, Universidade Federal do Pampa, Campus Itaqui, Rua Luiz Joaquim de Sá Britto, s/n - Bairro: Promorar, Itaqui, Rio Grande do Sul, CEP 97650-000, Brazil.
³ Laboratório de Síntese Orgânica Limpa, LASOL, Centro de Ciências Químicas, Farmacêuticas e de Alimentos (CCQFA), Universidade Federal de Pelotas, Campus Universitário, S/N - Prédio/Bloco: 30 e 32, Capão do Leão, Rio Grande do Sul, CEP 96160-000, Brazil.
⁴ Centro de Ciências Químicas, Farmacêuticas e de Alimentos, Universidade Federal de Pelotas, Campus Universitário, S/N - Prédio/Bloco: 30 e 32, Capão do Leão, Rio Grande do Sul, CEP 96160-000, Brazil.
⁵ Laboratório de Avaliações Farmacológicas e Toxicológicas Aplicadas às Moléculas Bioativas, LaftamBio Pampa, Universidade Federal do Pampa, Campus Itaqui, Rua Luiz Joaquim de Sá Britto, s/n - Bairro: Promorar, Itaqui, Rio Grande do Sul, CEP 97650-000, Brazil; Department of Nutrition, Universidade Federal do Pampa, Campus Itaqui, Rua Luiz Joaquim de Sá Britto, s/n - Bairro: Promorar, Itaqui, Rio Grande do Sul, CEP 97650-000, Brazil. Electronic address: marinaprigol@gmail.com.

PMID: 30366679
DOI: 10.1016/j.jtemb.2018.10.015

Abstract

Neurodegeneration in Parkinson's disease appears to be caused by multiple factors, including oxidative damage and an increase in acetylcholinesterase expression that can culminate in loss of dopaminergic neurons. A selenium-containing quinoline derivative, 7-chloro-4-(phenylselanyl) quinoline (4-PSQ), shows important pharmacological actions mainly attributed to its antioxidant and anticholinesterase properties. Thus, this study investigated the neuroprotective effect of 4-PSQ in a model of Parkinson's-like disease induced by rotenone (ROT) in Drosophila melanogaster and verified whether these effects are related to selenium levels. Adult flies were divided into: [1] control, [2] 4-PSQ (25 μM), [3] ROT (500 μM), and [4] 4-PSQ (25 μM) + ROT (500 μM) groups and exposed to a diet containing ROT and/or 4-PSQ for 7 days, according to their respective groups. Survival, behavioral, and ex vivo analyses were performed. Dopamine levels, reactive species levels (RS), lipid peroxidation (LPO), superoxide dismutase (SOD) and catalase (CAT) activity, and proteic thiol (PSH) and non-proteic thiol (NPSH) content in the head region were analyzed, while acetylcholinesterase (AChE) activity and selenium levels in the head and body regions were analyzed. 4-PSQ was able to reverse the ROT-induced deficits in flies, reestablish dopamine and selenium levels, reverse cholinergic deficits, improve motor function, and ameliorate mortality. Furthermore, 4-PSQ also reduced RS levels and LPO, and restored the activities of the antioxidant enzymes, SOD and CAT. Interestingly, a positive relationship between dopamine and selenium levels could be seen. Our results demonstrate the neuroprotective effect of 4-PSQ, and we suggest that the compound may act via different mechanisms, such as improving antioxidant defenses and consequently reducing oxidative damages, as well as having an anticholinesterase action, which together can prevent dopamine depletion, as these actions were correlated with the presence of selenium in the 4-PSQ molecule.

Keywords: Anticholinesterase; Antioxidant; Dopaminergic; Neurotoxicity; Quinoline; Selenium.

MeSH terms

Acetylcholinesterase / metabolism
Animals
Antioxidants / metabolism
Dopamine
Drosophila melanogaster
Lipid Peroxidation / drug effects
Oxidation-Reduction / drug effects
Oxidative Stress / drug effects
Parkinson Disease / metabolism*
Protein Carbonylation / drug effects
Quinolines / therapeutic use*
Selenium / metabolism
Superoxide Dismutase / metabolism

Substances

Antioxidants
Quinolines
quinoline
Superoxide Dismutase
Acetylcholinesterase
Selenium
Dopamine