Vol.:(0123456789) 1 3 Archives of Toxicology (2020) 94:1443–1460 https://doi.org/10.1007/s00204-020-02702-9 REVIEW ARTICLE Recent aspects of the efects of zinc on human health Christos T. Chasapis 1,2  · Panagoula‑Stamatina A. Ntoupa 3  · Chara A. Spiliopoulou 3  · Maria E. Stefanidou 3 Received: 27 February 2020 / Accepted: 5 March 2020 / Published online: 12 May 2020 © Springer-Verlag GmbH Germany, part of Springer Nature 2020 Abstract Zinc (Zn) is one of the most important essential nutrients of great public health signifcance. It is involved in numerous bio- logical functions and it is considered as a multipurpose trace element, due to its capacity to bind to more than 300 enzymes and more than 2000 transcriptional factors. Its role in biochemical pathways and cellular functions, such as the response to oxidative stress, homeostasis, immune responses, DNA replication, DNA damage repair, cell cycle progression, apoptosis and aging is signifcant. Zn is required for the synthesis of protein and collagen, thus contributing to wound healing and a healthy skin. Metallothioneins are metal-binding proteins and they are potent scavengers of heavy metals, including Zn, and protect the organism against stress. Zn defciency is observed almost in 17% of the global population and afects many organ systems, leading to dysfunction of both humoral and cell-mediated immunity, thus increasing the susceptibility to infection. This review gives a thorough insight into the most recent evidence on the association between Zn biochemistry and human pathologies, epigenetic processes, gut microbial composition, drug targets and nanomedicine. Keywords Zinc binding enzymes · Zinc defciency · Metal toxicity · Nutrition · Oxidative stress · Nanoparticles Introduction A total of 2–3 g of Zn is contained in the human body making Zn the second most abundant transition metal in humans and many other living organisms after Fe and the second most abundant divalent cation after calcium. Zn is a trace element essential for the growth and development of all organisms. It is an essential antioxidant mineral for preventing formation and reactive response of free radicals, which are unstable atoms that contain one or more unpaired electrons that can damage cells, leading to the progression of chronic and degenerative diseases (Pae et al. 2012). Zn plays a crucial role in proper cellular function, including diferentiation, cell division, cell growth, cellular transport, endocrine and immune system, transcription, pro- tein synthesis, RNA and DNA synthesis and DNA replica- tion (Ackland and Michalczyk 2016). It is found in many tissues, with the majority in the testes, muscle, liver, bones and brain (Glutsch et al. 2019). It is abundantly present in the synaptic vesicles and it plays essential roles in learning and memory. Also Zn is a cofactor for more than 1000 enzy- matic reactions and more than 2000 transcription factors (Chasapis et al. 2012b). Zinc fnger proteins are one of the most abundant groups of proteins and have a wide range of molecular roles in health and disease states. Zn is required for the structural stability of Zn fnger proteins (Zfp). Zn fnger proteins are transcriptional factors and are capable of modulating DNA, RNA and other proteins. More specifcally, they regulate signal transduction, cell diferentiation or proliferation, cell adhesion and transcription. Moreover, Zn maintains the enzymatic structure at the active site of CuZn-superoxide dismutase (SOD) (Santos et al. 2019). They are classifed as Class I Cys2His2 (C2H2) proteins, Class II Cys4 (C4) Zn fnger proteins, and Class III (C6) Zn fnger proteins called Zn cluster proteins. Zn is extensively involved in normal function of the immune system, wound repair, insulin syn- thesis and secretion and blood pressure regulation (Freitas et al. 2017; Lin et al. 2017). It is a biological regulator of * Maria E. Stefanidou mstefan@med.uoa.gr 1 NMR Center, Instrumental Analysis Laboratory, School of Natural Sciences, University of Patras, Patras, Greece 2 Institute of Chemical Engineering Sciences, Foundation for Research and Technology-Hellas (FORTH/ICE-HT), Patras, Greece 3 Department of Forensic Medicine and Toxicology, School of Medicine, National and Kapodistrian University of Athens, 75, Mikras Asias Street, 11527 Goudi, Athens, Greece