Minocycline exerts a neuroprotective action against 6-OHDA-induced neurotoxicity: in vivo and in vitro studies

Background: Parkinson’s disease (PD) is a chronic neurological disorder characterized by the loss of dopaminergic neurons in the substantia nigra pars compacta. The oxidative stress and inflammation, among other factors, are involved in the mechanisms of cell death in PD. We studied the neuroprotective properties of minocycline (Mino), focusing on its behavioral, neurochemical and immunohistochemical effects. Besides, Mino effects were also studied on an in vitro model of PD, as well as on the release of MPO in human neutrophils, and also its antioxidant activity. Methods: We used in vivo (unilateral injection of 6-OHDA into the right striatum) and in vitro (SH-SY5Y cells) models of PD. For the in vivo model, male Wistar rats were divided into the following groups: sham-operated (SO), 6-OHDA-lesioned and untreated and 6-OHDA-lesioned and treated with Mino (10 and 25 mg/kg, p.o., 7days). The animals were evaluated for behavioral, neurochemical and immunohistochemistry alterations. We also focused on Mino cytoprotective effects, as evaluated by its antioxidant and anti-inflammatory effects (nitrite determination and MPO release). Results: Mino (10 and 25 mg/kg, p.o.) significantly reversed the decrease in striatal DA and DOPAC contents, the alteration in apomorphine-induced rotational behavior and the locomotor activity observed in 6-OHDA-lesioned rats, indicative of neuroprotection. Besides, it decreased the immunoreactivity for TNF-alpha in the hippocampus. In SH-SY5Y cells, Mino increased cells viability, as evaluated by the MTT assay, and significantly decreased the high nitrite levels observed in the cells after 6-OHDA-induced cytotoxicity. Mino presented anti-inflammatory and antioxidant effects as evaluated by inhibition of MPO release (an inflammatory marker) on human neutrophils and DPPH assay. Conclusion: Minocycline exerts neuroprotective effects in vivo and in vitro, decreasing dopaminergic cell loss, through mechanisms that are a consequence of Mino anti-inflammatory and antioxidant properties, pointing out to its potential application for the treatment of neurodegenerative diseases as PD. Â