The protective effect of (S)-trolox–carnosine on a human neuroblastoma SH-SY5Y cell culture under the impact of heavy metals

Abstract

Evaluation of the dose-dependent effects of heavy metals on the viability of a human neuroblastoma SH-SY5Y cell culture showed that 50% cell death was observed in the presence of 5 × 10^–4 М lead, 5 × 10^–6 М cadmium, 5 × 10^–5 М cobalt, and 10^–5 М molybdenum. The presence of these metals led to an increase in the level of reactive oxygen species (ROS) (from 39% to 74% in the cases of lead and cobalt, respectively). We revealed a cytoprotective effect against toxic heavy metals (HMs) of a new synthetic compound, (S)-6-hydroxy-2,5,7,8-tetramethylchroman-2-carbonyl-β-alanyl-L-hystidine. This compound is a combination of carnosine with a water-soluble vitamin E analog, trolox (S-trolox–carnosine, S-TC). S-TC efficiently increased the cell viability in the presence of any of the studied metals, which correlated with a decrease in the proportion of necrotic cells and with efficient inhibition of ROS formation. Trolox also had a large cytoprotective effect under toxic conditions caused by lead, cadmium, and cobalt. The protective activity of carnosine under these conditions was significantly lower than the effects of trolox or trolox–carnosine. In general, these results revealed the greater cytoprotective effect of S-trolox–carnosine in the presence of heavy metals as compared to its precursors, trolox and carnosine.