Serum Indicators of Oxidative Damage from Embedded Metal Fragments in a Rat Model

Abstract

Injuries suffered in armed conflicts often result in embedded metal fragments. Standard surgical guidance recommends leaving embedded fragments in place except under certain circumstances in an attempt to avoid the potential morbidity that extensive surgery often brings. However, technological advances in weapon systems and insurgent use of improvised explosive devices now mean that practically any metal can be found in these types of wounds. Unfortunately, in many cases, the long-term toxicological properties of embedded metals are not known, further complicating treatment decisions. Because of concerns over embedded metal fragment injuries, the U.S. Departments of Defense and Veterans’ Affairs developed a list of “metals of concern” for these types of injuries. In this study, we selected eight of these metals including tungsten, nickel, cobalt, iron, copper, aluminum, lead, and depleted uranium to investigate the long-term health effects using a rodent model developed in our Institute to study embedded fragment injuries. In this report, we show that metals surgically implanted into the gastrocnemius muscle of laboratory rats to simulate a shrapnel wound induce a variety of cytokines including IFN-γ, IL-4, IL-5, IL-6, IL-10, and IL-13. TNF-α and KC/GRO were not affected, and IL-1β was below the limit of detection. Serum levels of C-reactive protein were also affected, increasing with some metals and decreasing with others. The TBARS assay, an assessment of lipid peroxidation, demonstrated that implanted aluminum and lead increased markers of lipid peroxidation in serum. Taken together, the results suggest that serum cytokine levels, as well as other indicators of oxidative damage, may prove useful in identifying potential adverse health effects of embedded metals.