Effects of myricetin against cadmium-induced neurotoxicity in PC12 cells

Abstract

Cadmium (Cd) is one of the most prevalent toxic metals widely found in the environment. Cd induces toxicity and apoptosis in various organs and cells. The nervous system is one of the primary organs targeted by Cd. Cd toxicity is correlated with induction of severe oxidative stress. Myricetin, a natural product, has been found to exert protective effects against various disease conditions. The present study aimed to evaluate the potential protective effects of myricetin on Cd-induced neurotoxicity in PC12 cells. The cells were pretreated with myricetin in the absence and presence of Cd. The viability of cells was assessed using the MTT assay. Markers of oxidative stress were investigated by the lipid peroxidation (LPO), glutathione (GSH) content, and total antioxidant capacity (TAC). Moreover, activation of caspase 3 was examined by Western blot analysis. Myricetin could significantly enhance the viability of PC12 cells. Pretreatment of the cells with myricetin, prior to Cd exposure, showed a significant decrease in the levels of LPO whereas GSH and TAC levels were increased. In addition, the activity of caspase-3 was notably prevented by myricetin. These findings revealed that myricetin has protective effects on Cd-induced neurotoxicity in PC12 cells, which can be linked to its antioxidant potential, inhibition of LPO, and prevention of caspase-3 activation.

Keywords: PC12 cells; cadmium; lipid peroxidation; myricetin; oxidative stress.

Graphical Abstract

Figure 1

Effect of cadmium (Cd) on cell viability in PC12 cells. The cells were treated with various concentrations of Cd (2.5, 5, 10, and 20 μM) and cell viability was examined by MTT assay. Results are presented as the mean ± SD (n = 5). ^*P < 0.05, ^***P < 0.001 compared with control.

Figure 2

Effect of myricetin on the cell viability (a) and level of MDA (b) in PC12 cells under Cd toxicity. The cells were preincubated with various concentrations of myricetin (0.25, 0.5, and 1 μM) for 24 h and then treated with Cd (10 μM) for 24 h. The results are presented as the mean ± SD (n = 3–5). ^###P < 0.001 compared with the control group. ^**P < 0.01, ^***P < 0.001 compared with the Cd group.

Figure 3

Effect of myricetin on GSH content (a) and total antioxidant capacity (TAC) (b) in PC12 cells under Cd toxicity. The cells were preincubated with myricetin for 24 h and then treated with Cd (10 μM) for 24 h. The results are reported as the mean ± SD (n = 3). ^###P < 0.001 compared with the control group. ^*P < 0.05, ^***P < 0.001 compared with the Cd group.

Figure 4

Effect of myricetin on activation of caspase-3 in PC12 cells under Cd toxicity. The cells were preincubated with myricetin for 24 h and then treated with Cd (10 μM) for 24 h (a). The density of cleaved caspase-3 was determined (b). The results are presented as the mean ± SD (n = 3). ^###P < 0.001 compared with the control group. ^*P < 0.05, ^***P < 0.001 compared with the Cd group.