Regulation of COX-2 expression by selected trace elements and heavy metals: Health implications, and changes in...

Trace elements or trace metals are essential components of enzymes, proteins, hormones and play a key role in biochemical processes, cell growth and differentiation, as well as in neurotransmission, affecting human physiology. In nature there are also heavy metals that exhibit toxic effects on the human body, including the brain. The importance of trace elements has been established in neurodegenerative disorders, schizophrenia, depression among others. In parallel, an important regulatory element in the above diseases is cyclooxygenase-2 (COX-2), a modulator of the arachidonic acid (AA) pathway, and a cause of neuroinflammation, and glutamate (Glu) dysregulation, affecting calcium (Ca) metabolism in cells. This review presents the effects of major trace elements and heavy metals on COX-2 expression. Calcium (Ca), zinc (Zn), cadmium (Cd), vanadium (V), nickel (Ni), copper (Cu), and iron (Fe) can potentially increase COX-2 expression, inducing neuroinflammation and Glu excitotoxicity; while magnesium (Mg), lithium (Li), and selenium (Se) can potentially decrease COX-2 expression. The associated mechanisms are described in the article.