Analysis of Cadmium, Epigallocatechin Gallate, and Vitamin C Co-exposure on PC12 Cellular Mechanisms

Exposure to cadmium (Cd) is a risk factor to health impairments, wherein its cytotoxicity is attributed to induction of oxidative stress. Usage of anti-oxidants, however, can help lessen the damaging effects of Cd. The effect of Cd interaction with low concentration of dietary anti-oxidants, l -ascorbic acid and (−)-epigallocatechin gallate (EGCG), to PC12 cellular mechanisms was examined. The expected toxicity of Cd was observed on PC12 cells but addition of l -ascorbic acid ameliorated this effect. On the other hand, addition of EGCG was able to increase the cytotoxicity of Cd and to decrease the protective effect of l -ascorbic acid against Cd. Increase in LDH activity and decrease in free sulfhydryl levels indicated cell membrane damage and oxidative stress, respectively, in Cd- and EGCG-Cd-treated cells. Downregulation of pro-apoptotic proteins (pro-caspase-9, p53, and ERK1) was observed in cells treated with Cd alone and EGCG-Cd, while upregulation of autophagy-linked proteins (p62 and pBeclin1) was found on l -ascorbic acid–Cd combination treatments. These findings indicate that Cd causes cells to undergo an autophagy-enhanced cell death; low-concentration EGCG and l -ascorbic acid promotes cell survival individually; however, interaction of EGCG with Cd showed enhancement of Cd toxicity and antagonism of l -ascorbic acid efficiency.