Ação antioxidante e efeito neuroprotetor de polissacarídeos sulfatados

Abstract

Neurodegenerative diseases are the result of multifactorial biological mechanisms, involving both exogenous and endogenous causes. Due to the increase in life expectancy and the predicted growth of dementia conditions, there is a growing concern in seeking more effective prevention and treatment for neurodegeneration. Oxidative stress has been shown to be an important factor in the development and progression of these diseases, due to intrinsic characteristics of nervous tissue, such as low regenerative capacity and high energy demand. Marine algae are sources of various bioactive molecules, especially sulfated polysaccharides (SP). These compounds are important for the survival of algae and have significant biological activities, such as antioxidant and anti-inflammatory properties. These properties can be useful in the treatment of neurodegenerative diseases. The SP from algae have shown promise as an alternative for neuroprotection. Nine species of algae were identified whose SPs exhibit antioxidant action under different conditions. Forty-four fractions rich in sulfated polysaccharides (FRP) were obtained. These FRP were evaluated for their cytotoxicity in Neuro-2A cells at different concentrations (0.1, 0.25, 0.5, and 1 mg/mL). From each FRP, two concentrations were selected, one higher and one lower, which showed MTT reduction values equal to or greater than 80%, for analysis of protection against oxidative damage induced by hydrogen peroxide. To select the FRP that would be evaluated for possible protective mechanisms employed, the results of yield parameters, cytotoxic effect, and neuroprotective potential in cell culture were considered to construct a Score. The possible mechanisms involved were analyzed through the determination of hydrogen peroxide scavenging potential and the effect on the expression of genes in the antioxidant pathway (Keap1, Nfr2, Sod1, Cat, Gpx, Hmox1, Gclc, Gclm) and the subunits of the transcription factor NFκB (Nfkb1 and Rela). Additionally, the antioxidant protection capacity was evaluated in an in vivo model (zebrafish). Of the 44 FRP evaluated, 42 did not show cytotoxic effects against Neuro-2A cells at at least one of the evaluated concentrations. All evaluated algae had FRP that protected Neuro-2A cells from oxidative damage induced by hydrogen peroxide. Furthermore, through the Score, it was possible to observe that brown algae had the best results. Based on these data, four FRP (DJ 1.2, SF 0.5, SS 1.3, and DM 1.0) were selected for the evaluation of the possible mechanisms involved. The data obtained demonstrate that the mechanisms used by these samples range from direct action on oxidant molecules to the modulation of endogenous antioxidant mechanisms, promoting an increase in the expression of genes related to the translation of antioxidant enzymes and a reduction in the expression of genes related to a pro-inflammatory and pro-oxidant response. Additionally, these polysaccharides were able to promote protection against oxidative stress in an in vivo model. These data are important for the development of future evaluations of these molecules, as they provide knowledge about their potential neuroprotective effect, possible mechanisms, and antioxidant activity in more complex organisms.