Neuroprotective effects of melatonin against neurotoxicity induced by intranasal sodium dimethyldithiocarbamate administration in mice

Autor(es)

Mack, Josiel Mileno ^{[1, 2]} ; Moura, Tainara de Menezes ^[1] ; Bobinski, Franciane ^[3] ; Martins, Daniel Fernandes ^[3] ; Cunha, Rodrigo A. ^{[4, 5]} ; Walz, Roger ^[2] ; Fernandes, Pedro Augusto ^[6] ; Markus, Regina Pekelmann ^[6] ; Dafre, Alcir Luiz ^[7] ; Prediger, Rui Daniel ^[1]

Afiliação do(s) autor(es)

^[1] Fed Univ Santa Catarina UFSC, Ctr Biol Sci, Dept Pharmacol, Grad Program Pharmacol, Florianopolis, SC - Brazil

^[2] Univ Fed Santa Catarina, Dept Med Clin, Grad Program Med Sci, Florianopolis, SC - Brazil

^[3] Univ Southern Santa Catarina UNISUL, Expt Neurosci Lab LaNEx, Grad Program Hlth Sci, Palhoca, SC - Brazil

^[4] Univ Coimbra, Fac Med, Coimbra - Portugal

^[5] Univ Coimbra, CNC Ctr Neurosci Coimbra, Coimbra - Portugal

^[6] Univ Sao Paulo, Inst Biosci, Dept Physiol, Sao Paulo, SP - Brazil

^[7] Fed Univ Santa Catarina UFSC, Ctr Biol Sci, Dept Biochem, Florianopolis, SC - Brazil

• Tipo de documento: Artigo Científico
• Fonte: NeuroToxicology; v. 80, p. 144-154, SEP 2020.
• Citações Web of Science: 0

Resumo

Exposure to fungicide ziram (zinc dimethyldithiocarbamate) has been associated with increased incidence of Parkinson's disease (PD). We recently demonstrated that the intranasal (i.n.) administration of sodium dimethyldithiocarbamate (NaDMDC, a more soluble salt than ziram) induces PD-like behavioral and neurochemical alterations in mice. We now investigated the putative neuroprotective effects of melatonin on behavioral dificits and neurochemical alterations induced by i.n. NaDMDC. Melatonin treatment (3, 10 or 30 mg/kg, i.p.) was given 1 h before NaDMDC administration (1 mg/nostril) during 4 consecutive days and we evaluated early (up to 7 days) and late (up to 35 days) NaDMDC-induced behavioral and neurochemical alterations. Melatonin treatment protected against early motor and general neurological impairments observed in the open field and neurological score of severity, respectively, and late deficits in rotarod test. Melatonin prevented the NaDMDC-induced alterations in the striatal tyrosine hydroxylase immunocontent. Melatonin also protected against increased levels of oxidative stress markers (4-hydroxynonenal and 3-nitrotyrosine) in the striatum, as well as the NaDMDC-induced increase of 4-hydroxynonenal and TNF, markers of oxidative stress and inflammation, respectively, in the olfactory bulb. These results further detail the mechanisms underlying NaDMDC toxicity and demonstrate the neuroprotective effects of melatonin against the neuronal damage induced by NaDMDC. (AU)

• Processo FAPESP: 13/13691-1 - Eixo imune-pineal: integrando a biologia do tempo em condições fisiológicas, fisiopatológicas e patológicas
• Beneficiário: Regina Pekelmann Markus
• Modalidade de apoio: Auxílio à Pesquisa - Temático