METHOD: Cognitive decline was determined by Montreal Cognitive Assessment (MoCA). Oxidative stress markers (malondialdehyde-MDA and superoxide dismutase-SOD) were determined and DNA damage was assayed using Alkaline Comet Assay. Toenail samples were taken and analyzed using ICP-MS to determine trace element levels.
RESULTS: A total of 62.1 % of subjects had cognitive impairment. Subjects with cognitive impairment had significantly higher levels of MDA and DNA damage as compared to the group with normal cognitive function; MDA (2.07 ± 0.05 nmol/L vs 1.85 ± 0.06 nmol/L) (p<0.05) and DNA damage (% Tail Density, 14.52 ± 0.32 vs 10.31 ± 0.42; Tail Moment, 1.79 ± 0.06 vs 1.28 ± 0.06) (p<0.05 for all parameters). However, the level of SOD among subjects with cognitive impairment (6.67 ± 0.33 u.e/min/mg protein) was lower than the level among those with normal cognitive functions (11.36 ± 0.65 u.e/min/mg protein) (p<0.05). Multiple logistic regression revealed the predictors for cognitive impairment among the subjects were DNA damage (Adjusted odd ratio [OR], 1.37; 95% confidence interval [CI], 1.18-1.59), level of trace elements in toenails namely, lead (OR, 2.471; CI, 1.535-3.980) and copper (OR, 1.275; CI, 1.047-1.552) (p<0.05).
CONCLUSION: High levels of lead and copper can lead to increase in oxidative stress levels and are associated with DNA damage that eventually could be associated with cognitive decline.
MATERIALS AND METHODS: One hundred and twenty primary school children were included. They were divided into caries and caries-free groups. Unstimulated whole saliva was collected from each participant using spitting method. The salivary elements were measured using an Atomic Absorption Spectrophotometer. Descriptive statistics, bivariate and Pearson's correlation analysis were performed.
RESULTS: Salivary Cu and Zn levels were significantly higher in children with dental caries compared to those caries-free (p < 0.05). Moreover, these elements had a positive correlation with dental caries (Cu: r=0.698, p<0.001; Zn: r=0.181, p<0.05). No significant variations in Mn and Fe were observed between caries and caries-free group (p>0.05). Additionally, there were significant differences in salivary Zn and Fe among different age groups (p<0.05) and highly significant differences in salivary Cu, Mn and Fe among different ethnic groups (p<0.001). However, all elements exhibited no significant differences between males and females.
CONCLUSION: The salivary Cu and Zn levels showed significant differences between caries and caries-free groups. The findings also revealed significant variations in the levels of salivary Cu, Mn and Fe among different ethnic groups and salivary Zn and Fe among different age groups.
HYPOTHESIS: Intracellular copper levels have been reported to correlate with tumor pathogenesis and affect the sensitivity of cancer cells to cytotoxic chemotherapy. We hypothesized that intracellular copper levels may affect the sensitivity of oral cancer cells to curcumin.
METHODS: We analysed the correlation between intracellular copper levels and response to curcumin treatment in a panel of OSCC cell lines derived from oral cancer patients. Exogenous copper was supplemented in curcumin insensitive cell lines to observe the effect of copper on curcumin-mediated inhibition of cell viability and migration, as well as induction of oxidative stress and apoptosis. Protein markers of cell migration and oxidative stress were also analysed using Western blotting.
RESULTS: Concentrations of curcumin which inhibited 50% OSCC cell viability (IC50) was reduced up to 5 times in the presence of 250 µM copper. Increased copper level in curcumin-treated OSCC cells was accompanied by the induction of intracellular ROS and increased level of Nrf2 which regulates oxidative stress responses in cells. Supplemental copper also inhibited migration of curcumin-treated cells with enhanced level of E-cadherin and decreased vimentin, indications of suppressed epithelial-mesenchymal transition. Early apoptosis was observed in combined treatment but not in treatment with curcumin or copper alone.
CONCLUSION: Supplement of copper significantly enhanced the inhibitory effect of curcumin treatment on migration and viability of oral cancer cells. Together, these findings provide molecular insight into the role of copper in overcoming insensitivity of oral cancer cells to curcumin treatment, suggesting a new strategy for cancer therapy.