Zinc is a powerful immunomodulatory trace element, and its deficiency in the body is closely associated with changes in immune functions and viral infections, including SARS-CoV-2, the virus responsible for COVID-19. The creation of new forms of zinc delivery to target cells can make it possible to obtain smart chains of food ingredients. Recent evidence supports the idea that the optimal intake of zinc or bioactive compounds in appropriate supplements should be considered as part of a strategy to generate an immune response in the human body. Therefore, controlling the amount of this element in the diet is especially important for populations at risk of zinc deficiency, who are more susceptible to the severe progression of viral infection and disease, such as COVID-19. Convergent approaches such as micro- and nano-encapsulation develop new ways to treat zinc deficiency and make zinc more bioavailable.

This current study was conducted to investigate whether bone tissue impairment induced by early life exposure to cadmium (Cd) during postnatal development could result from disruption to zinc (Zn) metabolism. For this reason, the offspring from mothers receiving either tap water, Cd, Zn or Cd + Zn during gestation and lactation periods were euthanized at PND21 and PND70. At the end of the lactation period (PND21), our results showed that exposure to Cd increased Cd accumulation and Zn depletion in the femur. Furthermore, calcium (Ca) level was reduced. At the molecular level, Cd induced an increase of MT-1 expression and caused an upregulation of ZIP2 accompanied with a down-regulation of ZnT5. Runx2, ALP, colα-1 and Oc mRNA levels were also decreased. In plasma, IGF-1 and osteocalcin concentrations were decreased. Further, Cd altered femoral growth by generating changes in the growth plate. Consequently, the toxic effect of Cd persisted at adult age (PND70) by decreasing bone volume (%BV/TV), bone mineral density (BMD) and Ca content and by increasing trabecular separation (Tb.Sp) in the distal femur. Interestingly, Zn supply provided total or partial corrections of several toxic effects of Cd. These data suggest that the increases of Zn bioavailability as well as the reduction of Cd accumulation in the femur following the changes in ZIP2 and ZnT5 expression are part of the mechanism involved in Zn protection against Cd toxicity on bone tissue.