Oxidative damage in metal fragment-embedded Sprague-Dawley rat gastrocnemius muscle

John F Kalinich; Vernieda B Vergara; Jessica F Hoffman

doi:10.1016/j.crtox.2022.100083

Oxidative damage in metal fragment-embedded Sprague-Dawley rat gastrocnemius muscle

Curr Res Toxicol. 2022 Jul 25:3:100083. doi: 10.1016/j.crtox.2022.100083. eCollection 2022.

Authors

John F Kalinich¹, Vernieda B Vergara¹, Jessica F Hoffman¹

Affiliation

¹ Internal Contamination and Metal Toxicity Program, Armed Forces Radiobiology Research Institute, Uniformed Services University, 4555 South Palmer Road, Bethesda, MD 20889-5648, USA.

Abstract

Injuries suffered in armed conflicts often result in wounds with embedded metal fragments. Standard surgical guidance has been to leave fragments in place except under certain circumstances; meaning that individuals may carry these retained fragments for their lifetime. Because of advancements in weapon design and the use of improvised explosive devices, the list of metals that could be found in a wound is extensive. In most cases the toxicological properties of these metals when embedded in the body are not known. To assess the potential damage embedded metals may cause to surrounding tissue, we utilized a rodent model to investigate the effect of a variety of military-relevant metals on markers of oxidative damage. The metals tested included tungsten, nickel, cobalt, iron, copper, aluminum, lead, and depleted uranium. Herein we report our findings on creatine kinase activity, lipid and protein oxidation, total antioxidant capacity, and glutathione levels in gastrocnemius homogenates from Sprague-Dawley rats surgically implanted with metal pellets for periods up to 12 months. Not all embedded metals affected the measured markers equally. However, metal-associated effects were seen at various times for muscle and serum creatinine levels, protein oxidation, total antioxidant capacity, and glutathione levels. No metal-induced effects on lipid peroxidation were observed. Taken together, these data suggest that subtle oxidative damage may be occurring in the muscle surrounding an embedded metal and indicates the need for medical surveillance of those individuals wounded by metal shrapnel.

Keywords: AAALAC, Association for Assessment and Accreditation of Laboratory Animal Care; AFRRI, Armed Forces Radiobiology Research Institute; AOPP, advanced oxidative protein products; Al, aluminum; Co, cobalt; Cu, copper; DU, depleted uranium; DoD, Department of Defense; Embedded metal; Fe, iron; GSH, glutathione; IACUC, Institutional Animal Care and Use Committee; Muscle; Ni, nickel; Oxidative damage; Pb, lead; Rat; Shrapnel; TAC, total antioxidant capacity; TBARS, thiobarbituric acid reactive substances; Ta, tantalum; USU, Uniformed Services University; W, tungsten.