Zinc as a Drug for Wilson's Disease, Non-Alcoholic Liver Disease and COVID-19-Related Liver Injury

Abstract

Zinc is the second most abundant trace element in the human body, and it plays a fundamental role in human physiology, being an integral component of hundreds of enzymes and transcription factors. The discovery that zinc atoms may compete with copper for their absorption in the gastrointestinal tract let to introduce zinc in the therapy of Wilson's disease, a congenital disorder of copper metabolism characterized by a systemic copper storage. Nowadays, zinc salts are considered one of the best therapeutic approach in patients affected by Wilson's disease. On the basis of the similarities, at histological level, between Wilson's disease and non-alcoholic liver disease, zinc has been successfully introduced in the therapy of non-alcoholic liver disease, with positive effects both on insulin resistance and oxidative stress. Recently, zinc deficiency has been indicated as a possible factor responsible for the susceptibility of elderly patients to undergo infection by SARS-CoV-2, the coronavirus responsible for the COVID-19 pandemic. Here, we present the data correlating zinc deficiency with the insurgence and progression of Covid-19 with low zinc levels associated with severe disease states. Finally, the relevance of zinc supplementation in aged people at risk for SARS-CoV-2 is underlined, with the aim that the zinc-based drug, classically used in the treatment of copper overload, might be recorded as one of the tools reducing the mortality of COVID-19, particularly in elderly people.

Keywords: COVID-19; Wilson’s disease; drug therapy; non-alcoholic liver disease; zinc.

Scheme 1

Zinc metabolism is finely regulated in the body in order to limits its potential toxic effect. The zinc dietary intake is regulated in the intestine through several zinc transporters proteins (ZnT) and by iron-regulated transporter proteins (ZIP). Zinc bound to α2 -macroglobulin (a2m), albumin (alb) and other proteins and amino acid (AA) is distributed in the body. Zinc is prevalently stored in skeletal muscle, bone, liver and brain. Liver plays a central role in zinc metabolism and, in general hepatitis, liver disfunction or liver diseases are associated with low levels of this trace element. In the brain, zinc is necessary for the regular central nervous system functions.