Homeostasis is the regulatory mechanism for the expression of all genes, the function of all metabolic pathways, the utilization of any essential trace element (TEs), while its disruptions lead to many pathological states. The pathologies include cardiovascular disease, anaemia, diabetes, neurological disorders, and cell death. For this, copper and zinc are two of the major TEs involved in controlling the physiological and pathological processes in both humans and animals. Zinc deficiency, for instance, is linked with decreased body weight, decreased ability to metabolize glucose, and impaired immune function. By contrast, deficiency of copper can lead to several neurological disorders, oxidative stress, mitochondrial dysfunction, and changes in lipid metabolism. On the other hand, there excessive exposure can have adverse effects on health, including the development of epilepsy, neuronal excitability, genotoxic effects, and cellular toxicity. Moreover, dual biological functions of zinc further complicate the understanding of their roles in both health and disease. Such as, zinc has a neuromodulatory function and helps to control excitably in neurons, but sometimes zinc in the synapse, inhibit the functioning of inhibitory neurotransmitter and cause damage to the neurons. Likewise, in metabolic diseases, particularly diabetes mellitus, there is often dysregulation of the levels of zinc and copper, resulting in steel-like interactions; elevated levels of copper and reduced levels of zinc contribute towards the pathogenesis of both the disease and the progression of dementia. Despite this antagonistic relationship, both trace metals act synergistically as necessary derivatives of superoxide dismutase; therefore, both play a vital role in maintaining cellular antioxidant defense systems. Therefore, this review covers published articles from 1992-2025 with regard to zinc and copper in their dietary and nanoparticle forms in animal and human models to demonstrate their differing roles and how they complement one another, or conflict with one another.

Center of Advanced Innovation Technologies VŠB Technical University of Ostrava 708 00 Ostrava Poruba Czech Republic

Centre for Herbal Pharmacology and Environmental Sustainability Chettinad Hospital and Research Institute Chettinad Academy of Research and Education Kelambakkam Tamil Nadu 603103 India

Department of Biotechnology Graphic Era Dehradun Uttarakhand 248002 India

Department of Chemistry Faculty of Science University of Hradec Kralove Rokitanskeho 62 500 03 Hradec Kralove Czech Republic

Division of Microbiology Career Point University Hamirpur HP 176041 India

School of Applied and Life Sciences Uttaranchal University Dehradun 248007 India

School of Biological and Environmental Sciences Shoolini University Solan HP 173229 India

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