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.

Association between the Composite Dietary Antioxidant Index and Nonalcoholic Fatty Liver Disease: Evidence from National Health and Nutrition Examination Survey 2005-2016

“…Further dose-response studies on antioxidant compounds may be warranted to elucidate the relationship. However, concerning the independent association between intake of vitamin A, vitamin C, vitamin E, and zinc with NAFLD, our results align with several prior studies [52][53][54][55] . Reactive oxygen species (ROS) and lipid peroxidation directly damage hepatocytes by affecting membranes, proteins, and DNA.…”

Dietary zinc supplements: beneficial health effects and application in food, medicine and animals

“…157 Nowadays, zinc salts are considered one of the best treatments for patients with Wilson's disease. 158 The FDA has approved zinc for treating patients with Wilson's disease. Zinc with chelation is very effective in the treatment of Wilson's disease and has the advantage of very low toxicity and only minor side effects of gastric disturbances.…”

Mineral metabolism and ferroptosis in non-alcoholic fatty liver diseases

“…Metallothionein is also involved in zinc and copper interactions. A good example is the introduction of zinc salt supplements in the clinical treatment of Wilson's disease since high-dose zinc impedes intestinal absorption of copper by inducing metallothionein synthesis in intestinal cells and the shedding of these cells [187].…”