Protective effects of resveratrol, quercetin, and their glucuronide derivatives in an in vitro model of Mn- and Al-induced cytotoxicity in SH-SY5Y human neuroblastoma cells

Manganese and aluminium toxicity has been associated with the pathogenesis of neurodegenerative diseases. Simultaneously, resveratrol and quercetin have been suggested as potentially useful substances in the context of these conditions. Accordingly, we examined whether trans -resveratrol, quercetin, and their glucuronidated metabolites display protective effects against manganese- and aluminium-induced neurotoxicity in an in vitro model, employing the SH-SY5Y cell line. The results demonstrated that both metals harmfully influenced cell viability as they elevated lactate dehydrogenase release and decreased thiazolyl blue tetrazolium bromide reduction. Manganese and aluminium differentially affected apoptotic processes, changing the caspase-3 activity of SH-SY5Y cells. We observed that trans -resveratrol and quercetin displayed protective action against toxicity produced by metals. However, the impact varied and depended on the form/concentration of polyphenols. Regarding manganese, quercetin (5, 10 μM), trans -resveratrol 3-O-β-D-glucuronide, and quercetin 3-O-β-D-glucuronide (both at 20 and 30 μM) were effective against metal-induced alterations of lactate dehydrogenase secretion, whereas trans -resveratrol (5 μM) and quercetin (5, 10, 20 μM) normalized caspase-3 activity. When SH-SY5Y cells were treated with aluminium, trans -resveratrol, quercetin (both at 5 and 10 μM), and trans -resveratrol 3-O-β-D-glucuronide (30 μM) diminished the negative influence of metal on lactate dehydrogenase efflux, while 5 μM quercetin 3-O-β-D-glucuronide improved thiazolyl blue tetrazolium bromide reduction. None of the used polyphenols recovered aluminium-evoked disturbances of caspase-3 activity. Our results confirmed the promising neuroprotective potential of trans -resveratrol, quercetin, and their derivatives against manganese and aluminium toxicity, and may have significant applications for further research related to the harmful impact of the metals on the central nervous system.