Do Repeated Pulmonary Exposures to Zinc Induce Sensitization or Adaptation?

Principal Investigator: Dr. Ramon Molina, former research scientist in Physiology in the Department of Environmental Health at Harvard T.H. Chan School of Public Health.

Cerium Chloride
Zinc Chloride

Project objective: To investigate the effects of repeated pulmonary exposures to zinc chloride (ZnCl2) on subsequent responses to zinc or cerium exposures. The researchers aimed to determine whether prior exposure to ZnCl2 alters the inflammatory and oxidative stress responses to subsequent exposures to zinc or cerium ions.

Project’s alignment with the Hoffman Program on Chemicals and Health mission: By investigating the inflammatory and oxidative stress responses in rats exposed to zinc chloride (ZnCl2) and cerium (CeCl3) metals, the researchers aim to provide insights into the potential risks associated with repeated exposures to metal contaminants.

Some key takeaways:

  • The researchers conducted a study using rats to understand how repeated exposure to a metal called zinc chloride (ZnCl2) affects the body’s response to zinc and cerium, which are also metals. The rats were divided into different groups, and some of them were exposed to ZnCl2 while others received a harmless saline solution. This exposure was done by putting the substances directly into their lungs. After a short break, the rats were exposed to either more ZnCl2, cerium (CeCl3), or saline.
  • The researchers collected fluid from the lungs of the rats and analyzed it to look for signs of lung injury, inflammation, and oxidative stress (a condition caused by harmful molecules in the body). They found that the rats exposed to multiple doses of saline followed by ZnCl2 and CeCl3 had increased levels of markers associated with inflammation. However, the rats that were repeatedly exposed to a lower dose of ZnCl2 before being exposed to higher doses of ZnCl2 or CeCl3 showed even stronger inflammatory responses. This was evident from increased levels of specific cells and substances related to inflammation.
  • Furthermore, all exposures to ZnCl2 or CeCl3 caused a significant decrease in a ratio called GSH/GSSG, which indicates the presence of oxidative stress. The researchers concluded that prior exposure to zinc ions makes the body more responsive to subsequent exposures to zinc and cerium ions. They suggested that this increased sensitivity could be due to a decrease in the body’s antioxidant defenses, as shown by the reduction in the GSH/GSSG ratio.

Products resulting from Hoffman support: Watson-Wright C, Queiroz P, Rodrigues S, Donaghey TC, Brain JD, Molina RM. Repeated pulmonary exposures to zinc ions enhance inflammatory responses to subsequent metal exposures. Exp Lung Res. 2018 May-Jun;44(4-5):252-261. doi: 10.1080/01902148.2018.1517837. Epub 2018 Oct 8. PMID: 30295553; PMCID: PMC6351161.