Effects of chronic copper exposure on the cuproptosis pathway

Aim: Copper is a heavy metal that can show toxic effect even at very few doses so adverse effects may occur if exposed to copper. Because of its redox active property, its capacity to form reactive oxygen species is known toxicity mechanism for copper. Considering that increased copper concentrations in the cell in the cuproptosis cell death pathway lead to cell death, it can be mentioned that there is an association relationship between copper exposure and the cuproptosis pathway. In this study, it was aimed to evaluate the effects of chronic copper exposure on the cuproptosis pathway. Method: For the purpose of the study, 26 individuals who worked/were working in a copper mine and 26 individuals without any heavy metal exposure history were included in the study. Expression levels of FDX1 and SLC31A1 genes, which have been proven to be associated with cuproptosis, were evaluated by qPCR in the serum of individuals. Gene expression levels were compared between the control group and the exposure group by statistical analysis, and comparisons were made in terms of demographic characteristics. The association between two genes was evaluated by correlation analysis. Results: As a result of the analysis, it was observed that FDX1 expression levels increased significantly in the control group (p<0,05). SLC31A1 expression levels were higher in the exposure group compared to the control group, but this value was not statistically significant (p>0.05). Age, smoking and exposure time parameters did not significantly affect gene expression levels (p>0.05). When the association between FDX1 and SLC31A1 expression levels in the exposure group was examined, a moderate positive correlation was found between the two genes and this value was very close to the significance value (p=0.055). Conclusion: As a result of the evaluations, it was concluded that chronic copper exposure has no effect on the cupoptosis pathway and that FDX1 and SLC31A1 genes are not reliable biomarkers for the detection of chronic copper exposure. These results were considered to be an idea for future studies in this area.